Pan Arab Journal of Oncology - Arab Medical Association Against ...

Pan Arab Journal of Oncology 

ISSN: 2070-254X 

Official Publication of the Arab Medical Association Against Cancer | www.amaac.info | vol 3; issue 1 | March 10 

INITIATIVE TO IMPROVE CANCER CARE IN THE ARAB WORLD 

Proceedings of the Symposium 

March 23 - 25, 2010 | Riyadh, KSA

editorial board < contents < 

¼ Editor-in-Chief 

Marwan Ghosn, MD, MBA / MHM 

> mghosn.hdf@usj.edu.lb 

> marwan.ghosn@cmc.com.lb 

Lebanon 

¼ Deputy Editor 

Sami Khatib, MD 

> skhatib@khcbi.jo 

Jordan 

¼ Associate Editors 

Khaled Al-Saleh, MD 

> gffccku@yahoo.com 

Kuwait 

Jamal Khader, MD 

> jkhader@khcc.jo 

Jordan 

Hussein Khaled, MD 

> khaled@internetegypt.com 

Egypt 

Nazar Makki, MD 

> ntmakki@yahoo.com 

Iraq 

¼ Design & Layout 

ZŽ na Khairallah 

> zenakhairallah@gmail.com 

¼ PAJO Editorial Board 

> editorinchief.pajo@yahoo.com 

ISSN: 2070-254X 

Pan Arab Publishing Company 

P. O. Box: 2509 

Amman 11953 - Jordan 

Beer Al SabeÕ St 

Shocair Medical Complex 

2nd Fl, office No. 201 

Phone + 962 6 566 78 53 

Fax + 962 6 562 38 53 

www.e-pamj.com 

AMAAC Introduction > 2 

International Advisory Board > 3 

Editorial > 4 

Special Thanks > 5 

Cancer Care in the Arab World | March 23-25, 2010 | Riyadh, KSA > 6 - 93 

News from the Arab World > 94 - 100 

¼ The 5th SEMCO-ASCO Conference 

¼ First EURO-ARAB Congress 

¼ The 3rd Regional Congress of Cancer and Blood Disorders of Childhood 

¼ International Symposium on New Frontiers in Breast Cancer 

¼ Conference on Topics in Therapeutic and Diagnostic Medical Physics 

¼ The 10th Pan Arab Cancer Congress 

¼ The 7th International Jordan Oncology (JOS) Conference 

Cancer Awareness Calendar > 102 

Instructions for Authors > 103 - 106 

www.amaac.info Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 < 1

amaac < 

AMAAC Introduction 

The Arab Medical Association Against Cancer (AMAAC) is a medical body that was established in 2001 as part of the Arab Medical 

Association where its main office is located in Cairo - Egypt, and it is also a continuation of the Arab Council Against Cancer that 

was founded in 1995. The Executive Committee of (AMAAC) is represented by two members who are named officially by the 

Oncology Society of each Arab Country. 

The Arab Medical Association Against Cancer aims at strengthening relationships between members in different Arab Countries to 

raise the level of cooperation in the field of oncology on both scientific and practical aspects. Exchanging information and researches 

between members through Regional and Arab Conferences and Publications. Holding Public Awareness Campaigns in the field of 

oncology that are organized by Arab Countries. Participating in scientific activities with International Oncology Societies. Finally, 

encouraging researchers and doctors to meet and exchange experiences together with finding training opportunities in the field of 

oncology inside and outside the Arab World. 

> The Executive Board of AMAAC 

Sami Khatib, MD (Jordan) Secretary General 

Hussein Khaled, MD (Egypt) Associate Secretary General 

Maha Manachi, MD (Syria) Associate Secretary General 

Khaled Al-Saleh, MD (Kuwait) Associate Secretary General 

Brahim El Gueddary, MD (Morocco) Associate Secretary General 

Said Al-Natour, MD (Jordan) Associate Secretary General (for financial affairs) 

> The officially nominated members of AMAAC by the Oncology Societies of Each Country 

Algeria Adda Bounedjar, MD 

Kamel Bouzid, MD 

Bahrain Abdulla Ajami, MD 

Egypt Hussein Khaled, MD 

Sherif Omar, MD 

Iraq Abdul MonÕ em Ahmed, MD 

Nezar Taha Maki, MD 

Jordan Sami Khatib, MD 

Said Al-Natour, MD 

Kuwait Khaled Al Khalidi, MD 

Khaled Al Saleh, MD 

Lebanon Marwan Ghosn, MD 

Nagi El-Saghir, MD 

Libya Hussein A Hashemi, MD 

Rammah Rumaihi, MD 

Morocco Ashraki Abdel Kader, MD 

Brahim Khalil El Gueddari, MD 

Oman Bassim Bahrani, MD 

Palestine Fuad Sabatin, MD 

Abdel Razaq Salhab, MD 

Saudi Arabia Om Al Kheir Abu Al Kheir, MD 

Shawki Bazarbashi, MD 

Sudan Hussein Mohammad Hamad, MD 

Kamal Eldein l Hamad, MD 

Syria Wassma Achawi, MD 

Maha Manachi, MD 

Tunisia Hamouda Boussen, MD 

Khalid Rahhal, MD 

Yemen Arwa Awn, MD 

Afif Nabhi, MD 

2 > Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info

international advisory board < 

Matti AAPRO, MD 

Director, Multidisciplinary Oncology Institute, Genolier, Switzerland 

Consultant to the Scientific Director, European Institute of Oncology, Milano, Italy 

Consultant, Division of Oncology, Geneva University Hospital 

Geneva - Switzerland 

Hoda ANTON-CULVER, PhD 

Professor & Chair 

Department of Epidemiology 

Professor, Department of Microbiology and molecular Genetics, 

School of Medicine 

Director, Genetic Epidemiology Research Institute 

University of California 

Irvine – USA 

Jean-Pierre ARMAND, MD 

Professor & General Director 

Centre de Lutte contre le Cancer 

Institut Claudius Regaud 

Toulouse – France 

Ahmad AWADA, MD 

Head of Medical Oncology Clinic 

Jules Bordet Cancer Institute 

Brussels - Belgium 

Patrice CARDE, MD 

Chairman Lymphoma Committee 

Gustave Roussy Institute 

Paris - France 

Franco CAVALLI, MD 

Professor & President UICC 

Director 

Oncology Institute of Southern Switzerland 

Bellinzona - Switzerland 

Joe CHANG, MD 

Assistant Professor of Radiation Oncology 

Clinical Service Chief, Thoracic Radiation Oncology 

MD Anderson Cancer Center 

Houston - USA 

William DALTON, MD 

President and Chief Executive Officer 

H.Lee Moffitt Cancer Center and Research Institute 

University of South Florida 

Florida - USA 

Jean-Pierre DROZ, MD 

Professor & Former Head of Oncology Department 

Centre de Lutte contre le Cancer Leon Berard 

Lyon - France 

Alexander EGGERMONT, MD, PhD 

Professor of Surgical Oncology 

Head of Department of Surgical Oncology 

Erasmus University Medical Center 

Daniel den Hoed Cancer Center 

Rotterdam - The Netherlands 

Jean-Pierre GERARD, MD 

Professor of Radiation Oncology 

General Director of Antoine-Lacassagne Cancer Center 

Lyon - France 

Joe HARFORD, MD 

Director of the Office of International Affairs 

National Institute of Health 

United States Department of Health and Human Services 

Bethesda - USA 

Alan HORWICH, MD 

Professor of Radiotherapy 

Section of Academic Radiotherapy and 

Department of Radiotherapy 

The Institute of Cancer Research 

London – United Kingdom 

Fritz JANICKE, MD 

Director Clinic & Polyclinic of Gynecology 

University Medical Center Hamburg-Eppendorf 

Hamburg – Germany 

Sima JEHA, MD 

Director of the Leukemia / Lymphoma Developmental Therapeutics 

Saint-Jude Children’s Research Hospital 

Memphis - USA 

Hagop KANTARJIAN, MD 

Professor of Medicine 

Chair of the Department of Leukemia 

The University of Texas - MD Anderson Cancer Center 

Houston - USA 

Fadlo R. Khuri, MD 

Professor and Chair, Department of Hematology and Medical Oncology 

Roberto C. Goizueta Distinguished Chair in Cancer Research 

Deputy Director, Clinical and Translational Research - Winship Cancer Institute 

Emory University School of Medicine 

Atlanta - USA 

Jean-Francois MORERE, MD 

Professor at University Paris XIII 

Head of the Department of Oncology 

Assistance Publique – Hôpitaux de Paris 

Paris - France 

Mack ROACH, MD 

Professor & Chairman 

Radiation Oncology & Professor of Urology 

University of California, Irvine 

California - USA 

Philippe ROUGIER, MD 

Professor of Medical Oncology 

Gastrointestinal Cancer 

Liver and Pancreas Tumors 

Ambroise-Pare Hospital 

Boulogne - France 

Youcef RUSTUM, PhD 

Chairman of the Department of Cancer Biology 

Roswell Park Cancer Institute 

Academic Research Professor 

Associate Vice Provost 

University at Buffalo 

New York - USA 

Sandra M. SWAIN, MD 

Medical Director, Washington Cancer Institute 

Washington Hospital Center 

Washington – USA 


editorial < 

Dear Colleagues, 

Despite considerable progress in its prevention and treatment, cancer remains a leading cause of morbidity and mortality in the Arab 

World. Cancer Figures in our countries need action. Reasons are unknown. Costs of treatments are unaffordable. Healthcare system 

doesn’t offer the optimal care. Patient and doctors are dissatisfied. The increase in medical tourism for a safer and less costly treatment 

is growing. Reports on the implementation of evidence-based medicine are few and even rare. The magnitude of the problem is not 

estimated, but we think that it is substantial. Challenges of the new environment are estimable. 

In its 1999 report Ensuring the Quality of Cancer Care, the Institute of Medicine's National Cancer Policy Board (NCPB) concluded, 

"Based on the best available evidence, some individuals with cancer do not receive care known to be effective for their condition." To 

address these concerns and the paucity of data on the quality of care for patients with cancer, the NCPB recommended establishing 

a quality monitoring system with capability of routine reporting of results. 

Motivated by the NCPB report, a number of initiatives were done to measure and improve the quality of care of patients with 

cancer. Examples include the joint effort of the National Cancer Institute and the National Quality Forum to identify and evaluate 

quality measures for cancer care; the American Society of Clinical Oncology Quality Oncology Practice Initiative; the Oncology 

Demonstration Project sponsored by the Centers for Medicare and Medicaid Services; and the National Initiative for Cancer Care 

Quality (NICCQ), which is led by American Society of Clinical Oncology in collaboration with multiple oncology professional 

societies, patient advocates, and researchers. 

We need to call for an urgent action to improve the Quality of care given to our patients. We need to optimize the treatment allocation, 

to ensure the access, the continuity of care and the integrity of the disease management with an acceptable cost effectiveness ratio. 

Changes of the healthcare system become a necessity and should face the challenges of the new environment. New solutions and 

strategies should be implemented. 

We are glad that the 1st issue of PAJO in 2010 is highlighting the initiative to improve Cancer Care in the Arab World. This meeting 

is hosted by National Guard Health Affairs jointly with Arab Medical Association Against Cancer in collaboration with national and 

international organizations and entities. 

We would like to thank all the contributors that worked hard to make this meeting happen. 

Marwan Ghosn, MD, MHHM 


special thanks < 

Thank you for all contributors, authors and reviewers of PAJO 

Pan Arab Journal ournal of Oncology 

Pan Arab Journal ournal of 

Oncology Pan Arab Journal ournal of Pan Oncology Arab Journal ournal of 

Pan Oncology Arab Journal ournal of 

Pan Oncology Arab Journal ournal of 

Pan Oncology Arab Journal of Oncology 

Official Publication of the Arab Medical Association Against Cancer | www.amaac.info | vol 1; issue 2 | June 08 

ISSN: 2070-254X 

ISSN: 2070-254X 

ISSN: 2070-254X 

Official Publication of the Arab Medical Association Against Cancer | www.amaac.info 

| vol 2; issue 1 | January 09 


Official Publication | vol of 2; issue the Arab 2 | Medical April 09 Association Against Cancer | www.amaac.info 

| vol 1; issue 3 | September 08 


Official Publication | vol 2; issue of the 3 | Arab September Medical 09 Association Against Cancer | www.amaac.info 

Official Publication | vol 2; issue of the 3 | Arab December Medical 09Association 

Against Cancer | www.amaac.info | vol 3; issue 1 | March 10 

Original Article 

Special Report 

Breast Cancer in Tunisia 

Highlights on the Speech and Language 

Special Issue Including the Proceedings of PACC 2009 

Pathologist’s role in Head and Health Neck Economics 

Cancer 

Review Articles 

Review 

A cost-minimization analysis Present & 9 Future of Radiation Oncology 

Soft Tissue Sarcoma in Young Individuals MENA 2008 

of 1st line polyCT regimens in Review of the Current Management Management of 

advanced NSCLC 

advanced advanced prostate cancer 

BLOM Beirut Marathon 08 

TH Special Issue Including the Proceedings of PACC 

Original Articles 

Review 

Meeting Highlights 

Treatment of Acute Lymphoblastic Leukemia ASCO 2008 Low dose Gemcitabine and Cisplatin 

PAN ARAB CANCER CONGRESS 

UICC 2008 in Advanced NSCLC 

Targeted Therapy Development 

PRAME and WT1 Genes expression 

7 - 9 May 2009 - Cairo, Egypt 

Angiogenesis review 

in CML Patients 

new publication 

Gerard Abadjian, MD 

Hamdi Abdel Azim, MD 

Wafaa Abdel-Hadi, MD 

A. Abdelkefi, MD 

Abdel Rahman M., MD 

Fatma Aboulkasem, MD 

Omalkhair Abulkhair, MD 

Mohsen Abdel Mohsen, MD 

Arabi Abdessamad, MD 

Noha Abdou, MD 

Miguel Aboud, MD 

Philippe Aftimos, MD 

Salim Adib, MD 

B. Allani, MD 

Bekadja Mohamed Amine, MD 

Elie Attieh, MD 

Fadwa Attiga, MD 

Ahmad Awada, MD 

Amal Baccar, MD 

Jean-Marc Bachaud, MD 

Thouraya Baroudi, MD 

Ali Bazerbachi, MD 

Amel Ben Ammar Elgaaied, MD 

Khaled Ben Rhomdhane, MD 

Alain Bernard, MD 

Ghislaine Bernard, MD 

Nizar Bitar, MD 

H. Boussen, MD 

Karim Chahed, MD 

Georges Chahine, MD 

Anouar Chaieb, MD 

Nicolas Chemali, MD 

Lotfi Cherni, MD 

Lotfi Chouchane, MD 

Elizabeth Cohen, MD 

Michel Daher, MD 

GŽ raldine Dalmasso, MD 

Kamal El-Dein Hamed Mohamed, MD 


www.amaac.info Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 < 5 



Dalia Darwish, MD 

Jean-Pierre Droz, MD 

Tayssir Eyada, MD 

Ahmad El-Ezzawy, MD 

Fadi Farhat, MD 

Nivine Gado, MD 

Marwan Ghosn, MD 

Heba Gouda, MD 

E. Gouider, MD 

Amin Haddad, MD 

Mohammad El-Hajj, MD 

Khaled Halahlah, MD 

Bechr Hamrita, MD 

Gregory Hangard, MD 

Colette Hanna, MD 

Mohamed A Hassan, MD 

Hassan A. Hatoum, MD 

Johan Hoebeke, MD 

Hesham El Hossieny, MD 

Ahmad Husari, MD 

Noha Ibrahim, MD 

Elias Jabbour, MD 

Sima Jeha, MD 

Maria Kabbage, MD 

Fadi El Karak, MD 

Joseph Kattan, MD 

M. Kefi, MD 

Jamal Khader, MD 

Hussein Khaled, MD 

Sami Khatib, MD 

Anne Laprie, MD 

Robert Launois, MD 

Katell Le Lay, MD 

Christelle Lemaitre-Guillier, MD 

Rami Mahfouz, MD 

Nazar Makki, MD 

Carole Massabeau, MD 

Andre Megarbane, MD 

While there’s 

there’s 

life, 

hope. 

(Cicero, 106 - 43 BC) 

Special Report: COMO 8 | Nov 2009 | Beirut, Lebanon 

Meeting Highlights 

InItIatIve to Improve CanCer Care In the arab World 

9th Pan Arab Original Oncology Articles Congress 

Effect of radiotherapy on malignant 

Best Best of ASCO Proteomic 2009 approach for the detection of pleural mesothelioma mesothelioma in in adjuvant, 

Proceedings of the Symposium 

breast cancer biomarkers. 

radical or palliative basis. 

March 23 - 25, 2010 | Riyadh, KSA 



Brahimi Mohamed, MD 

Mohsen Mokhtar, MD 

Walid Moukaddem, MD 

Jonathan Moyal, MD 

Elie Nasr, MD 

Fadi Nasr, MD 

Ghazi Nsouli, MD 

Ben Othman, MD 

Zaher Otrock, MD 

Martine Piccart, MD 

Shadi Qasem, MD 

Silvia Al Rabadi, MD 

Karim Rashid, MD 

Sami Remadi, MD 

Kamel Rouissi, MD 

Raya Saab, MD 

Ebtessam Saad El Deen, MD 

Laurence Ehret-Sabatier, MD 

Gamal Saied, MD 

Nagi El-Saghir, MD 

Ibrahim Saikali, MD 

Khaled El-Saleh, MD 

Ziad Salem, MD 

Lobna Sedky, MD 

Ali Shamseddine, MD 

Ahmad Shehadeh, MD 

Sana Al-Sukhun, MD 

Iyad Sultan, MD 

Ali Taher, MD 

Paul-Henri Torbey, MD 

Wafa Troudi, MD 

Virginie Vandenberghe, MD 

Alain Vergnenegre, MD 

Laure Vieillevigne, MD 

Besma Yacoubi-Loueslati, MD 

Mahmoud Yassein, MD 

Riad Younes, MD

cancer care in the arab world | march 23-25, 2010 | riyadh, ksa < 

Introduction 

This initiative aims at developing strategic recommendations to improve cancer 

care in the Arab countries. 

The inaugural meeting will be held on March 23-25, 2010 at the Four Seasons 

Hotel, Riyadh, KSA. This meeting is hosted by the National Guard Health Affairs 

jointly with Arab Medical Association Against Cancer in collaboration with national 

and international organizations and entities. 

In preparation to this meeting; working groups/ panels will be assembled to do 

the ground work and preparation for the launch of the initiative. The panels will 

have facilitators and members from various countries based on interest, expertise 

and nominations. While participants can hold an official status in their countries, 

the participation in this event does not carry official representation. 

The panels will work on performing situational analysis of a particular issue in 

the Arab World and suggest recommendations and specific action steps. These 

recommendations will be published and made available to all interested entities, 

organizations and individuals in the Arab Countries. 

Conference Objectives: 

1. To develop strategic recommendations to improve cancer care in the Arab 

countries. 

2. To facilitate networking, experiences sharing, cooperation and collaborative 

projects across the Arab world. 

3. To recommend specific action steps pertinent to our countries in order to 

improve cancer care in the region. 

When: March 23 -25, 2010 

Where: Four Seasons Hotel 

Organizers: 

• National Guards Health Affairs, KSA 

• Arab Medical Association Against Cancer (AMAAC) 

Participating Organizations: 

• International Union Against Cancer (UICC) 

CANCER PREVENTION 

AND EARLY DETECTION 

• Saudi Cancer Society 

• Saudi Ministry of Health 

• Arab-European School of Oncology 

• European Society of Medical Oncology 

Sponsoring Organizations: 

• Roche 

• Novartis 

• Bayer 

• GE Health 

• Others 

Initiative to Improve Cancer Care in the Arab World 

The Oncology Department at National Guards Health Affairs, Riyadh, KSA and the 

Arab Medical Association Against Cancer (AMAAC) are launching the “Initiative 

to Improve Cancer Care in the Arab World (ICCAW)”. 

This initiative aims at developing strategic recommendations to improve cancer 

care in the Arab countries. The inaugural meeting will be held on March 23-25 

at the Four Seasons Hotel, Riyadh, KSA. 

For more information and registration in the meeting visit www.iccaw.com or 

email at info@iccaw.com. 

Abdul Rahman Jazieh, MD, MPH 

Chairman, Scientific Committee 


Dr. Sami Al Khatib 

Co-Chairperson, Scientific Committee 


Dr. Omalkhair Abulkhair 

Co-Chairperson, Scientific Committee 



MANUAL OF CANCER PREVENTION AND EARLY DETECTION 

GUIDELINES IN THE ARAB COUNTRIES 

Editors 


Chairman, Department of Oncology 

King Abdulaziz Medical City 

Dr. Omalkhair Abulkhair 

Section Head, Division of Adult Medical Oncology 

Department of Oncology 

King Abdulaziz Medical City 

Introduction 

The Manual of “Cancer Prevention and Early Detection Guidelines in the Arab 

Countries” is a compilation of manuscripts written by experts and physicians 

who participated in the Second Cancer Prevention and Early Detection Day held 

by National Guards Health Affairs in Riyadh, KSA on October 22 -23, 2008. 

The manuscripts review the epidemiological data and risk factors for common 

cancer and discuss risk factors, prevention and early detection. The authors 

presented the best guidelines and recommendations available for our Arab 

Countries. It is known that there is a knowledge gap in this matter in term of 

having original, accurate and adequate information from our region. Nevertheless, 

initial steps to combat cancer should be taken while more specific data relevant 

to our region made available. 

We thank all the authors for their efforts and contribution and we encourage all 

physicians to take part in the fight against cancer which will be the epidemic of 

the 21st century. 


Chairman, Department of Oncology, King Abdulaziz Medical City 



Department of Oncology, King Abdulaziz Medical City 

Topics Index 

I. Cancer Epidemiology 

1. Epidemiology of Cancer in the Gulf Region 

2. Cancer Magnitude in Sham Countries 

II. Cancer Risk Factors 

1. Role of Diet in Cancer 

2. Oncologist Perspective on Tobacco Control: Historical View and Practical 

Guidelines 

3. Environmental Carcinogens and Pollution 

III. Breast Cancer 

1. Epidemiology, Prevention and Management Guidelines for Breast Cancer 

in Arab Countries 

2. The Role of MRI on Cancer Detection and Management: The Saudi Arabian 

Experience 

3. Role of Imaging in Early Detection: Is Mammography Still the Standard 

of Care 

4. The Use of MRI for the Early Detection of Breast Cancer 

5. Diet, Physical Activity and Obesity in the Prevention and Recurrence of 

Breast Cancer: Relevance to Saudi Arabian Women 

6. Challenges of Cancer Screening Program 

IV. Gynecological Oncology 

1. Endometrial Carcinoma 

V. GU Oncology 

1. Urinary Bladder Cancer 

2. Testicular Cancer 

3. Prostate Cancer 

VI. Head and Neck Cancer 

1. Oral Malignancies: Role of Prevention and Early Detection 

2. Thyroid Cancer Epidemiology and Prevention 

VII. Lung Cancer 

1. Lung Cancer Prevention and Early Detection 

VIII. GI Malignancies 

1. Esophageal Cancer 

2. Gastric Cancer 

3. Colorectal Cancer: Prevention and Early Detection 

4. Hepatocellular Carcinoma 

IX. Pediatric Malignancies 

1. Cancer Prevention and Early Detection in Pediatric Malignancies 

X. Role of Physicians in Cancer Prevention 

1. Role of Primary Care Physicians in the Fight Against Cancer 

2. Role of Primary Care Physicians in the Prevention and Early Detection of 

Cancer: An Oncologist Perspective 

Program 

1. Plenary sessions 1-3: Will include presentations by world experts in the 

related topics. They will address the topic in global fashion and reflecting 

on its relevance to our region. 

2. Breakout sessions: Will include the panel members with the help of the 

international experts from in the particular topics. It will be a chance for 

personal interaction among the facilitators, experts and panel members. The 

breakout session activities will include: 

a. Agreement on the consensus recommendations. 

b. Planning the next action step to be achieved in the next 12 month. 

c. Review and update available resources list. 

A document should be generated from the meeting in uniformed publishable format. 

4. Plenary Session 4 - 5: The panels will present their recommendations and 

action steps to all attendees. 

5. Satellite Symposia: Will address specific clinical topics of interest to the 

practicing physicians in order to have valuable attractive educational events 

for attendees and will be organized by sponsors. 

6. Social activities: Opening Ceremony dinner will be held on March 23 night. 

Gala dinner will be held in March 24 night. 



EPIDEMIOLOGY OF CANCER IN THE GULF REGION 

Khoja, T. 1 , Zahrani A. 2 

(1) Council of Health Ministers for GCC State 

(2) Gulf Center for Gulf Registration 

Corresponding Author: Dr. Tawfik A. M. Khoja 

Family Physician Consultant, Director General, Executive Board, Council of 

Health Ministers for GCC State, P.O. Box 54647 Riyadh 11524, Kingdom of 

Saudi Arabia 

E-mail: sgh@sgh.org.sa 

Introduction 

Cancer is the second most frequent cause of death in majority of the developed 

countries. It is emerging as a major public health problem in developing countries. 

The International Agency for Research on Cancer (IARC) estimates that, globally, 

nearly 11 million new cases of cancer and more than 6 million deaths from this 

disease occurred during 2002 with more than half of the cases arising in developing 

countries where resources for treatment and prevention are scarce. The rapid 

improvement in the field of health care together with the control of communicable 

diseases, increased life expectancy at birth, and with rapid socioeconomic changes 

resulting in modified lifestyles such as increased prevalence of tobacco use, 

decrease in physical activity and rapid uptake of unhealthy food habits has resulted 

in an increased incidence of cancer in the developing countries. 

Cancer registries are a unique source of information centre for any cancer control 

program. These data helps to allocate financial and manpower resources in cost-effective 

health care planning as well as in the design of early detection and prevention programs. 

The Gulf Center for Cancer Registration (GCCR) was established in 1997. The 

GCCR works under the jurisdiction of the Executive Office of the Health Ministers’ 

Council for GCC States. The main office is located in the premises of the Research 

Center, King Faisal Specialist Hospital and Research Center. The GCCR database, 

population-based incidence data is the largest aggregations in the Asia. Compiling 

data from the six national cancer registries representing the six Gulf countries: 

United Arab Emirates (UAE), Kingdom of Bahrain, Kingdom of Saudi Arabia 

(KSA), Sultanate of Oman, State of Qatar, and State of Kuwait. 

Objectives 

The primary objective of this study is to classify information on all cancer cases in 

order to produce statistics on the occurrence of cancer among GCC States’ nationals. 

Materials and Methods 

Data which include patient’s identification, demographic information, site of cancer, 

histology, stage, behavior and extent of the disease, basis of diagnosis and treatment 

methods are collected from the patient’s medical records based on clinical and 

histological diagnosis at the National Cancer Registry (NCR) in each of the GCC 

States. Data entry in CanReg4 software and data quality assurance are performed 

at each GCC State NCR before they sent to the GCCR main office for ensuring 

the accuracy of information reported and subsequently for annual data analysis. 

Crude Incidence Rates (CIR) and Age Standardized Rates (ASR) were calculated 

to compare cancer incidence between different countries. These rates are sensitive 

to changes in the number of reported cases due to underreporting and changes 

in the population structure. Therefore, there is a potential for some changes in 

cancer incidence rates in the GCC countries that did not have recent population 

census available for this report or those depend on fewer sources for cancer case 

identification. 

Overall cancer incidence in the GCC States 

From January 1998 to December 2004 there were 58,180 newly diagnosed cancer 

cases among the GCC States nationals reported from the six National Cancer 

Registries. 28,542 cases (49.06%) were males and 29,638 (50.94%) were females. 

Majority of cases (71.1%) were reported from KSA, followed by Oman (11.1%), 

Kuwait (6.8%), Bahrain (5.1%), UAE (3.8%), and Qatar (2.1%). 

Diagnosis of cancer based on histopathological confirmation in more than 95% of 

cases ranging from 85.2% in Kuwait to 97.4% in KSA indicating high degree of 

certainty of cancer diagnosis in tradeoff completeness of cancer registration in the 

GCC States. Other sources such as clinical, surgical, and radiological reports were 

rarely used as independent sources for cancer registration. Death certificate was 

used as independent source for cancer registration by Kuwait (13.2%) and Bahrain 

(5.7%), whereas other countries showed no preference to this type of data collection. 

Almost half of the cancer cases had either regional or distant metastasis at the 

time of diagnosis. Only 22.6% of patients presented with localized tumors and 

less than 2% with in situ, indicating the necessity of launching early detection 

programs in the Gulf region. Unknown extent of cancers was reported in about 

28% of patients ranging from 11.1% in UAE to 73.8% in Bahrain. 

In males, cancer incidence was highest in Bahrain and Qatar nationals with ASR of 

158.7 and 157 per 100,000 population for Bahraini and Qatari males, respectively. 

Kuwaiti males had an ASR of 132.6/100,000 population followed by Omani males 

with an ASR of 99.1/100,000 population, UAE males with ASR of 70.1/100,000 

population, and the lowest was among Saudi males (66.1/100,000 population). 

In females, cancer incidence was highest in Qatari women with ASR of 

165.2/100,000 populations, followed by Bahraini women with ASR of 

142.3/100,000 population, Kuwaiti women with ASR of 136.7/100,000 population, 

Omani women with an ASR of 85.4/100,000 population, UAE women with ASR 

of 81.9/100,000 population, and the lowest was among Saudi women (ASR 

62.9/100,000 population). 

Cancer is mainly the disease of old age. The mean age at diagnosis was 50.5 years 

(Standard Deviation ± 22.1). Total of 4029 cases (9.7%) were children below age 

of 15 years. Women develop cancer at an earlier age compared to men, the mean 

age for women was 47.7 years and 53.2 years for men. There is no significant 

difference in the age specific incidence rates in men and women of the GCC States. 

Most common cancers among nationals of the GCC States: 

Breast Cancer 

Breast cancer is the second most common cancer in the world and the most 

common cancer in women accounting to about 23% of all cancers. It is estimated 

that approximately one million cases of female breast cancer are diagnosed every 

year worldwide. Breast cancer is the most frequent cause of death among cancer 

deaths in women. An estimated 410,712 breast cancer deaths occurred in 2002. 


Breast cancer is the most common cancer in the GCC States. Between January 

1998 and December 2004, 6,882 breast cancer cases were reported from all GCC 

States accounted to 11.8% from all cancers and 22.7% from cancers among 

females. Bahrain reported the highest incidence of breast cancer. The ASR per 

100,000 women was 46.4 for Bahrain followed by Kuwait (44.3), Qatar (35.5), 

UAE (19.2), Oman (14.4), and KSA (12.9). 

Leukemia 

Leukemia is the 12th most common cancer in the world. The estimated number of 

newly diagnosed cases of leukemia was 300,522 cases in 2002 accounting to about 

2.8% of all new cancer cases with male to female ratio of 1.32: 1. In 2002, there were 

222,506 reported deaths attributed to leukemia accounting to 3.3% of all cancer deaths. 

In the GCC States, leukemia is the second most common cancer. Between January 

1998 and December 2004 there were 4,890 cases of leukemia accounted to 8.4% 

from all cancers in the GCC States. Leukemia incidence appeared to be slightly 

higher in males than females. Lymphoid leukemia was more common in males 

while myeloid leukemia was more common in females. 

Non-Hodgkin’s Lymphoma (NHL) 

NHL is the 10th most common cancer in the world. There are 300,571 new cases of 

NHL in 2002 accounting to 2.8% of all cancers. The male to female ratio is 1.39: 1. An 

estimated 171,820 deaths of NHL occurred in 2002 representing 2.6% of all cancer deaths. 

NHL is the third most common cancer in the GCC States. 4,830 NHL cases 

were reported from all GCC States accounted to 8.3% from all cancers between 

January 1998 and December 2004. NHL was the most common cancer in males 

and the third most common cancer in females (accounted to 10.4% and 6.3% for 

males and females respectively). Qatar reported the highest incidence of NHL 

among males and females (ASR was 11.8/100,000 for males and 8.0/100,000 for 

females), followed by Kuwait (ASR was 11.0/100,000 for males and 6.8/100,000 

for females). Oman and Bahrain males ranked third with ASR of 7.8/100,000, 

whereas Bahraini women ranked third and Kuwaiti women ranked fourth with 

ASR 5.4/100,000 and 4.4/100,000 respectively. KSA and UAE women ranked 

fifth with ASR of 4.1/100,000 each. KSA men ranked fifth and UAE men ranked 

sixth with ASR of 5.6 and 5.2 per 100,000 populations respectively. 

Colorectal Cancer 

Colorectal cancer is the third most common cancer in the world. In 2002, there 

were approximately one million new cases of colon and rectum cancer, 550,465 

males and 472,687 females worldwide. Colorectal cancer incidence ranked fourth 

in men and third in women. Approximately there were 529,000 deaths attributed 

to colon cancer in 2002. 

Colorectal cancer is the fourth most common cancer in the GCC States. 4,213 

colorectal cancer cases (7.2% from all cancers) were reported from all GCC 

States between January 1998 and December 2004. Kuwait reported the highest 

incidence of colorectal cancer (ASR was 15.1/100,000 population) among males 

followed by Bahrain (12.6/100,000), Qatar (11.6/100,000), UAE (6.6/100,000), 

KSA (5.0/100,000), and Oman (4.5/100,000), while Qatar reported the highest 

incidence of colorectal cancer (14.1/100,000) among females followed by Kuwait 

(12.7/100,000), Bahrain (7.3/100,000), UAE (5.3/100,000), KSA (4.7/100,000) 

and Oman (3.8/100,000). 

Thyroid Cancer 

Thyroid cancer is the 21st most common cancer in the world. The estimated total 

number of new thyroid cancer cases was 141,013 with an estimated 35,375 deaths 

from thyroid cancer representing 0.53% of all cancer deaths in 2002. Thyroid 

cancer is almost 3 times higher in females compared to males. 

Thyroid cancer is the fifth most common cancer in the GCC States. 3,458 thyroid 

cancer cases (5.9% from all cancers) were reported from all GCC States between 

January 1998 and December 2004. Thyroid cancer incidence was significantly 

higher among women compared to men in all of the GCC States. It ranked second 

most common cancer in women next to breast cancer. Qatar reported the highest 

incidence with ASR of 13.5/100,000 followed by Kuwait (7.7/100,000), Bahrain 

(7.6/100,000), UAE (6.0/100,000), Oman (5.9/100,000), and KSA (5.0/100,000). 

Liver Cancer 

Liver cancer is the sixth most common cancer in the world, with an estimated 

number of 626,162 (5.8% of new cancer cases) in 2002. Males are affected more 

than females with male to female ratio of 2.40: 1. Because of the very poor 

prognosis, number of deaths in 2002 (598,321) was not far short of the number of 

new cases, and it represents the third most common cause of death among cancer 

deaths accounting to 8.9% of cancer deaths. 

Liver cancer is the sixth most common cancer in the GCC States. 2,987 liver cancer 

cases (5.1% from all cancers) were reported from all GCC States between January 

1998 and December 2004. Liver cancer incidence was significantly higher among 

men compared to women in all of the GCC States. It ranked third most common 

cancer in men next to NHL and leukemia. Qatar had the highest incidence among 

men and women with ASR of 13.1/100,000 for males and 8.9/100,000 for females. 

Kuwaiti men ranked second (8.8/100,000), followed by KSA (6.9/100,000), Oman 

(6.4/100,000), Bahrain (5.2/100,000), and UAE (3.0/100,000). 

Lung Cancer 

Lung cancer is the commonest cancer in the world today accounting to 12.4% of 

all new cases. There are estimated to be 1,352,132 new cases in 2002. The disease 

is more common in men with a male to female ratio of 2.49: 1. Lung cancer is the 

leading cause of cancer related death in men and second in women. An estimated 

1,178,918 deaths accounting to 17.5% of all cancer deaths are occurred in 2002. 

Lung cancer is the seventh most common cancer in the GCC States. 2,481 lung 

cancer cases (4.9% from all cancers) were reported from all GCC States between 

January 1998 and December 2004. Lung cancer incidence was significantly higher 

among men compared to women in all of the GCC States. It ranked fourth most 

common cancer in men next to NHL, leukemia, and liver cancer. Bahrain had the 

highest incidence among men and women with ASR of 34.2/100,000 for males 

and 12.0/100,000 for females. Qatar ranked second, followed by Kuwait, Oman, 

and UAE. KSA reported the lowest incidence among males and females (5.0 and 

1.3 per 100,000 for males and females respectively). 

Stomach Cancer 

Stomach cancer is the fourth most common cancer in the world with an estimated 

number of 933,937 cases in 2002 (8.6% of new cancer cases). The male to female 

ratio is 1.83: 1. 

An estimated 700,349 (446,052 males and 254,297 females) stomach cancer 

deaths occurred in 2002. It is the second most frequent cause of death among 

cancer deaths accounting to 10.4% of cancer deaths. 

Stomach cancer is the eighth most common cancer in the GCC States. 2,424 



stomach cancer cases (4.1% from all cancers) were reported from all GCC States 

between January 1998 and December 2004. Stomach cancer incidence was more 

common in men compared to women in all of the GCC States. Oman had the 

highest incidence among men and women with ASR of 12.8/100,000 for males 

and 6.2/100,000 for females. Bahrain ranked second, followed by UAE, Qatar, 

and Kuwait. KSA reported the lowest incidence among males and females (2.8 

and 1.7 per 100,000 for males and females respectively). 

Prostate Cancer 

Prostate cancer is the fifth most common cancer in the world and the second 

importance in men. The estimated total number of new cases in 2002 is 679,023 

accounting to 11.7% of cancers in men. With an estimated 221,002 deaths prostate 

cancer is the sixth leading cause of cancer death in men. This represents 5.8% of 

all cancer deaths in men. 

Prostate cancer is the 9th most common cancer in the GCC States. 1,721 prostate 

cancer cases were reported from all GCC States between January 1998 and 

December 2004 accounted to 3.0% from all cancers and 6.0% from cancers among 

males. Bahrain reported the highest incidence of prostate cancer. The ASR per 

100,000 men was 14.1 for Bahrain followed by Kuwait (12.3), Oman (9.6), Qatar 

(9.4), UAE (6.4), and KSA (4.0). 

Cervical Cancer 

Cancer of cervix is the second most common cancer in women in the world. 

Almost half a million newly diagnosed cases of cervical cancer are estimated 

every year accounting to about 10% of all cancers in women. Cervical cancer 

is the third most frequent cause of death among cancer deaths in women. An 

estimated 273,500 cervix cancer deaths occurred in 2002 accounting to about 9% 

of all cancer deaths in women. 

Cervical cancer is the 10th most common cancer in the GCC States. Between 

January 1998 and December 2004, there were 1,279 cervical cancer cases reported 

from all GCC States accounted to 2.2% from all cancers and 4.3% from cancers 

among females. Qatar reported the highest incidence of cervical cancer. The ASR 

per 100,000 women was 6.8 for Qatar followed by Bahrain (5.9), Oman (5.7), 

UAE (5.4), Kuwait (4.8), and KSA (2.2). 

Ovarian Cancer 

Ovarian cancer is the sixth most common cancer among women. In 2002, there 

were 204,499 newly diagnosed ovarian cancer cases accounting to 5.8% of all 

cancers among women. Ovarian cancer is also the seventh most common cause 

of death among cancer deaths in women. In 2002 there were 124,860 deaths 

attributed to ovarian cancer accounting to 4.3%. 

Ovarian cancer is the 11th most common cancer in the GCC States. Between 

January 1998 and December 2004, 1,180 ovarian cancer cases were reported 

from all GCC States accounted to 2.0% from all cancers and 4.0% from cancers 

among females. Bahrain reported the highest incidence of ovarian cancer. The 

ASR per 100,000 women was 7.4 for Bahrain followed by Qatar (6.7), Kuwait 

(5.9), Oman (5.5), UAE (4.4), and KSA (2.3). 

Conclusion 

The GCCR is a demonstration of the value of collaborative efforts among the 

region countries to establish epidemiological data about cancer that could be used 

in various ways in cancer control efforts. 

ROLE OF DIET IN CANCER 

Al-Sukhun, S. 1 

(1) University of Jordan, Amman 

Corresponding Author: Dr. Sana Al-Sukhun, MD, MSc 

Assistant Professor of Medicine, Department of Hematology/Oncology 

University of Jordan, P.O. Box 5321 Amman 11183, Jordan 

E-mail: salsukhun@yahoo.com 

Cancer is an increasing health problem, not only for industrialized countries but 

also for most other parts of the world. 

The large differences in cancer rates among countries, striking changes in these 

rates among migrating populations, and rapid changes over time within countries 

indicate that some aspect of lifestyle or environment is largely responsible for the 

common cancers in Western countries(1). 

Stomach cancer is one of the most common cancers worldwide. Almost twothirds 

of the cases occur in developing countries and 42% in China alone(1). The 

geographical distribution of stomach cancer is characterized by wide international 

variations; high-risk areas (Age adjusted incidence rate (ASR) in men, >20 per 

100,000) include East Asia (China, Japan), Eastern Europe, and parts of Central 

and South America. Incidence rates are low ( Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info

Dietary fat has been hypothesized to be the key factor because national consumption 

is correlated with the international differences(6). However, detailed analyses 

in large prospective studies have not supported an important role of dietary 

fat. Instead, positive energy balance, reflected in early age at menarche and 

weight gain as an adult, is an important determinant of breast and colon cancers, 

consistent with numerous studies in animals(7&8). As a contributor to positive 

energy balance, and possibly by other mechanisms, physical inactivity has also 

been shown to be a risk factor for these diseases and in part accounts for the 

international differences (9&10). Although the percentage of calories from fat in 

the diet does not appear related to risk of colon cancer, greater risks have been 

seen with higher consumption of red meat, suggesting that factors other than fat 

per se are important. in prospective trials(11). On the other hand, a long standing 

belief in the protective role of fruits and vegetables was not confirmed. Taken 

together, the evidence supports a role for the triad of diet, body mass index and 

exercise in carcinogenesis. 

The Women Health Initiative (WHI) study is A randomized, controlled, primary 

prevention trial conducted at 40 US clinical centers from 1993 to 2005(12). 

A total of 48 835 postmenopausal women, aged 50 to 79 years, without prior breast 

cancer, were randomly assigned to the dietary modification intervention group (40% 

[n = 19 541]) or the comparison group (60% [n = 29 294]). The intervention was 

designed to promote dietary change with the goals of reducing intake of total fat 

to 20% of energy and increasing consumption of vegetables and fruit to at least 5 

servings daily and grains to at least 6 servings daily. Comparison group participants 

were not asked to make dietary changes. Surprisingly, that intervention did not 

result in a statistically significant reduction in invasive breast cancer risk over an 

8.1-year average follow-up period. However, the nonsignificant trends observed 

suggesting reduced risk associated with a low-fat dietary pattern indicated that 

longer, planned, nonintervention follow-up may yield a more definitive comparison. 

That same study failed to confirm the protective effect of normal levels of vitamin 

D against colorectal cancer suggested previously by the nurses’ health study(13). 

However, there were major limitations of that trial. Calcium and vitamin D was 

given as a combination. One of the limitations was just the fact that it was seven 

years, and that’s quite a short time in the development of colorectal cancer. It may 

be almost wishful thinking to believe that something like vitamin D or calcium 

could have an effect that quickly. Also, 69% of the women in the study were 

taking calcium supplements on their own, in both the placebo group and the active 

group, which causes huge misclassification. The controversial result from one of 

the best well designed trials speaks for the complexity of conducting prospective 

trials to address the role of a single nutrient in cancer. 

The evidence does not only support a role for the triad in carcinogenesis, but also 

in mortality from cancer(14). In a prospectively studied population of more than 

900,000 US adults, increased body weight was associated with increased death 

rates for all cancers combined and for cancers at multiple specific sites, including 

esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same 

was true for death due to non-Hodgkin’s lymphoma and multiple myeloma. The 

authors estimated that current patterns of overweight and obesity in the United 

States could account for 14 percent of all deaths from cancer in men and 20 percent 

of those in women. Even more interesting were data suggesting midrange intake 

of most major energy sources was associated with best survival after treatment 

of breast cancer, and extremes were associated with less favorable outcomes(15). 

Recent data confirmed that vitamin E supplements, selenium supplements, or the 2 

of them taken together did not reduce the risk of developing prostate cancer (16). 

If anything, there was a small trend towards an increase in the number of prostate 

cancer cases for the men randomized to take vitamin E, and a small increase in 

the number of cases of type I I diabetes mellitus in men taking only selenium. 

In light of the above discussion, moderation of diet (quantity and quality) seems 

the most reasonable approach to adopt throughout life. 

References 

1. Parkin, D. M. et al. Global cancer statistics, 2002. CA Cancer J Clin 2005. 

2005 Mar-Apr;55(2):74-108. 

2. Kolonel LN et al. Association of diet and place of birth with stomach cancer 

incidence in Hawaii Japanese and Caucasians. Am. J. Clin. Nutr. 1981, 34: 

2478-2485. 

3. Tannenbaum A. The initiation and growth of tumours: Introduction, Effects of 

undernutrition. Am J Cancer 1940, 35 : 335-350. 

4. Lavik PS, and Baumann CA. Further studies o the tumor promoting action of 

fat. Cancer Res. 1943, 3: 749-756. 

5. Doll R, Peto R. Avoidable risks of cancer in the United States. J Natl Cancer 

Inst 1981;66:1196-1265. 

6. Overview and perspective in human nutrition. Willett WC. Asia Pac J Clin Nutr. 

2008;17 Suppl 1:1-4. Review. 

7. Hunter DJ, Willett WC. Diet, body size, and breast cancer. Epidemiol Rev 

1993;15:110-132. 

8. Chute CG, Willett WC, Colditz GA et al. A prospective study of body mass, 

height, and smoking on the risk of colorectal cancer in women. Cancer Causes 

Control 1991;2:117-124. 

9. Martinez ME, et al. Physical activity, body size, and colorectal cancer in women. 

Am J Epidemiol 1996;143:S73a. 

10. Giovannucci E, et al. Physical activity, obesity, and risk for colon cancer and 

adenoma in men. Ann Intern Med 1995;122:327-334. 

11. Giovannucci E, et al. Intake of Fat, Meat, and Fiber in Relation to Risk of 

Colon Cancer in Men. Cancer Res. 1994, 54: 2390-2397. 

12. Prentice RL, et al. Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer 

The Women's Health Initiative Randomized Controlled Dietary Modification Trial. 

JAMA. 2006;295:629-642. 

13. Wactawski-Wende J, et al, Calcium plus Vitamin D Supplementation and the 

Risk of Colorectal Cancer. N Engl J Med 354:684, February 16, 2006. 

14. Calle EE et al. Overweight, Obesity, and Mortality from Cancer in a 

Prospectively Studied Cohort of U.S. Adults, N Engl J Med 2003;348:1625-38. 

15. Goodwin P et al. Diet and Beast Cancer: Evidence That Extremes in Diet Are 

Associated with Poor Survival. J Clin Oncol 2003, 21:2500-2507. 



EPIDEMIOLOGY, PREVENTION AND MANAGEMENT GUIDELINES 

FOR BREAST CANCER IN ARAB COUNTRIES 

Nagi S. El Saghir, MD, FACP 1 , Omalkhair Abulkhair, MD 2 

(1) American University of Beirut Medical Center, Beirut, Lebanon 

(2) King Abdulaziz Medical City for National Guard, Riyadh, KSA 

Corresponding Author: Nagi S. El Saghir, MD, FACP 

Hematology-Oncology, American University of Beirut Medical Center 

Cairo Street, Ras Beirut, Beirut, Lebanon 

E-mail: nagi.saghir@aub.edu.lb 


Department of Oncology (Mail code 1777), King Abdulaziz Medical City for 

National Guard, P.O. Box 22490, Riyadh 11426, Kingdom of Saudi Arabia 

E-mail: abulkhairo@ngha.med.sa 

Abstract 

Background: Breast cancer is the most common cancer among women in Arab 

countries. Management varies according to human and financial resources, as 

well as available facilities. 

Materials and Methods: Literature review of publications on the epidemiology, 

prevention and treatment of breast cancer in Arab countries. Presentations and 

discussions summarized from various oncology meetings. 

Results: Breast cancer represents an average of one-third of female cancers in 

Arab countries. Incidence continues to rise and has reached up to 50/100.000 

women in Gulf countries and highest in Lebanon at 69/100000 women per year. 

Around 50% of cases are below the age of 50 years. Over 60% of cases present 

with advanced disease. However, number of advanced cases has started to decrease 

and more cases are being diagnosed at earlier stages because of recent awareness 

and early detection campaigns done in many Arab countries. Radiation therapy 

remains concentrated in major cities and large numbers of patients have to travel 

long distances to get adequate care. Multidisciplinary management is practiced 

only in major university hospitals and in the few available cancer centers. 

Conclusions: More efforts towards primary prevention are recommended. 

Secondary prevention includes awareness campaigns and early detection. Raising 

awareness, promoting attention to breast symptoms, breast self examination and 

clinical breast examination are recommended to reduce locally advanced breast 

cancer. In addition, screening mammography is recommended in countries with 

adequate resources. Although the starting age of screening mammography is 

controversial, we recommend to start at age 40 because 50% of cases of breast 

cancer in Arab countries occur in women below the age of 50. More group 

discussions and multidisciplinary management between individual physicians 

caring for women with breast cancer are needed. 

Introduction 

Cancer prevention and early detection are the most effective ways to control 

disease, alleviate sufferings, prolong survival, and eventually cure patients with 

cancer. Cancer prevention and early detection ultimately reduces the incidence of 

cancer as well as morbidity and mortality from cancer. Early detection of breast 

cancer is considered as an important element of prevention of the disease. The 

improvement in breast cancer survival observed in industrialized nations in recent 

decades have been attributed to early detection by screening as well as to timely 

and effective treatment.1 

Consequently, breast cancer mortality which had been relatively unchanged from 

1930s through 1980s has dropped by 1.4% to 3.1% / year between 1990 and 2003 

in the US. 2 Cancer has become a national health priority according to the WHO 

in the Eastern Mediterranean Region. The general public, as well as healthcare 

professionals, have noted that breast cancer has become one of the most important 

health problems for women in Arab countries. 3,4,5 

Approximately, 15% of all breast cancer cases can be attributed to familial and 

genetic influences.6 Most known risk factors for breast cancer can be linked 

to hazardous effects of prolonged exposure to estrogens7 such as early age at 

menarche, late age at menopause,7 small number of children and nulliparity, late 

age at first birth8 and little or no breast feeding9,10 which have all been associated 

with an increased risk of developing breast cancer. Although several retrospective 

studies have suggested that induced abortion is related to an increased risk of 

this disease, this is not seen in prospective studies11 and its status as a breast 

cancer risk is unclear. Long term use of hormone replacement therapy has been 

associated with increased risk of developing breast cancer12 but apparently not 

use of oral contraceptives.12-15 

However, meta-analysis of all the data (Leslie Berstein, et al) ≥ ten years of use of 

the relative risk 1.38 (these women were 1.38 times as likely to get breast cancer 

as those who had not used the pill). The primary concern is for women who start 

their period before age eleven. Those who also begin having regular periods much 

faster, so, prolonged use of estrogen containing pills is more likely to harm this 

subgroup.16 So far, there is no evidence that the use of mega-dose of hormone 

infertility treatment are hazardous to the breast.15,17 High breast density has 

been described as an important marker of breast cancer risk.18,19 

History of proliferative benign breast disease is also related to increased risk of 

breast cancer20 especially those who underwent biopsies and those women in 

whom a typical hyperplasia was found in such biopsies.21 Therefore, in summary, 

breast cancer risk can be allocated to one of four groups: family history/genetic, 

reproductive/hormonal proliferative, benign breast disease with dysplasia, and 

mammographic density. Recently, it is believed that high-fat diet is not related per 

se to breast cancer risk22,23 but overall caloric intake and obesity in particular with 

weight-gain pattern, are related to increased breast cancer risk with differentiate 

effects between pre and post menopausal women.24,25 

Women with breast cancer may have advanced disease at diagnosis and some of 

reasons for such presentations are summarized in Table 1. 

Table 1: Reasons For Presentation As Advanced Disease 

Lack of knowledge on breast cancer risk factors 

Misconception about breast cancer screening 

Fear of cancer 

Shyness and fear of social implications 

Beliefs and fatalistic attitudes 

Lack of health care facilities 

2. Disease Epidemiology 

Breast cancer is the most common cancer diagnosed in US women and the second 

leading cause of death of cancer in US women.1 The good news is that mortality 

from breast cancer has recently dropped slightly. This decrease has been attributed, 

in part, to mammographic screening.1, 2 Breast cancer has been reported as the 

most common cancer among women from many hospitals and medical centers in 


Arab countries. Hospital-based registries, several regional and national registries 

have recently been in place and reported their data. Researchers have reported data 

in either abstract form or meeting presentations and some reported in peer-reviewed 

local or international journals. Many national registries now publish their data 

as annual reports in a booklet format. In this manuscript, we review and update 

the available data on breast cancer epidemiology from Arab countries. 26, 27 

Breast cancer is the most frequent cancer in Arab women constituting 14% to 42% 

of all women cancers. Age-Adjusted Standardized incidence rates (ASR) were 

reported to vary from 9.5 to 50 cases per 100.000 women per year. Median age at 

presentation is 48-52 years and 50% of cases are below the age of 50; whereas only 

25% of cases in industrialized nations are below the age of 50 years, and 50% of 

the cases are above the age of 63 years, 1, 2 thus it appears breast cancer in Arab 

countries presents almost 10 years younger than that in USA and Europe26,27 

Age-adjusted standardized incidence rates (ASR) for breast cancer have increased 

in many Arab countries such as Lebanon (from 20 in 1996 to 46.7 in 1998 and 

even 69 in 2003), Jordan (ASR increased from 7.6/100.000 women in 1982 to 

32.8/100000 in 1997), Palestinians (ASR up by 93%), Egypt ASR up to 49.6. 

Reports from the Gulf Center for Cancer Registration (GCCR) which represented 

data from six Gulf countries: Kingdom of Saudi Arabia, United Arab Emirates, 

Kingdom of Bahrain, Sultanate of Oman, State of Qatar and State of Kuwait, 

revealed that breast cancer is the most common in the GCC states between January 

1998 to December 2004. 6,882 breast cancer cases were reported from all GCC 

states accounted to 11.8% from all cancer and 22.7% from cancers among women. 

Bahrain reported the highest incidence. 

The ASR per 100,000 women was 46.4 followed by Kuwait 44.3, Qatar 35.5, 

UAE 19.2, Oman 14.4 and KSA 12.9. 28 Despite the low breast cancer incidence 

in the Kingdom of Saudi Arabia (KSA), it is the most common cancer and it 

ranked number one in Saudi female population for the past 5 consecutive years 

(Saudi National Cancer Registry, 2000 – 2004). Data on female patients with 

invasive breast carcinoma reported from different regions in Saudi Arabia revealed 

that most patients were between 40 – 50 years of age and were predominantly 

premenopausals. Although the rates are still below those in industrialized nations, 

they are rising and expected to reach the same levels. Changes may be due to 

Westernized life style changes including dietary habits, lack of exercise and 

urbanization, delay of ages of marriage and first pregnancy from the late teens 

and early twenties to the late twenties and even early thirties, respectively, as 

well as and decrease of the practice of breast feeding by Arab women. Advanced 

disease is commonly seen at presentation and in young women, diagnosis of breast 

cancer may be delayed because of decreased awareness as well as and low index 

of suspicion from their primary physicians. 29 

Young age at presentation has been shown to be a bad prognostic factor in two 

publications from Lebanon and Saudi Arabia.30-31 (Figure-1) 

Figure-1 Young Age Confers a Worse Prognosis in Breast Cancer 

3. Risk Factors 

A number of breast cancer risk factors have been well established for many decades, 

notably those related to hormonal and reproductive exposures.7-8 For example, 

nulliparity late age at first childbirth, early age at menarche and use of hormone 

replacement therapy are all associated with increased risk.7-11 Additionally, the 

association of a family history of breast cancer with increased risk of the disease 

has long been established.32-33 The increased awareness of family history is 

enhanced partly by the establishment of the high risk, high penetrance BRCA1 

and BRCA2 germline mutations.34 Other risk factors pertaining to personal 

medical history has been established. These include diagnosis of atypical ductal 

hyperplasia and lobular carcinoma in situ.35 Prolonged exposure to birth control 

pills in premenopausal women, and especially hormone replacement therapy in 

post-menopausal women increase the risk of breast cancer. Other risk factors 

include radiation exposure, pollution and exposure to carcinogenic compounds 

such as pesticides and even smoking are suspected. Westernized dietary habits, 

increase consumption of animal fats and decreased fibers, fruits and vegetables, 



as well as overweight and lack of exercise are known to increase breast cancer 

incidence among Asian immigrants to USA, Europe and Australia. Many of those 

risk factors are thought to apply to women in Arab countries. Only scattered studies 

on genetic mutations of BRCA-1, BRCA-2 and other oncogene mutations are 

available from Arab countries.36-37 

4. Presenting Signs and Symptoms 

The most common presentation in our countries is a breast lump or nodule, 

usually non-painful but may be associated with pain. Size of the lump depends 

on whether it was accidentally noted or whether the woman examines her breasts 

regularly. Other symptoms include changes in color or shape of the skin such as 

redness, ulceration and therapy of skin, nipple retraction or discharge of blood 

may be presenting complaints. A palpable mass in the axilla is not an uncommon 

presentation in cases of locally advanced breast cancer or without breast mass. 

Inflammatory breast cancer presents with a rapidly growing inflamed, thickened 

and red overlying breast skin. The data has shown that in many Arab countries 

that 50-80% of breast cancer is Arab countries present with advanced disease at 

presentation. More than 50% were Stage II and III while ductal carcinoma insitu 

represents Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info

6. Management and Treatment Guidelines: Multidisciplinary Approach 

Breast cancer management must be composed of a multidisciplinary team that 

involves different specialty: breast surgeon/oncologist surgeon, medical oncologist, 

radiation oncologist, pathologist, psychologist, social worker, health educator and 

plastic surgeon. If a full team is not available, multi-disciplinary approach should 

be practiced by whoever is present. Even if the hospital where a breast cancer 

patient is treated has only a surgeon and a radiologist and pathologist, or a surgeon 

and radiologist and an oncologist, or a surgeon and a radiologist and a radiation 

oncologist, they should meet and discuss their patient’s management. Every 

effort should be made to have a pathologist available. Discussion and exchange 

information with physicians working at major cancer centers should be encouraged. 

If there is no multi-disciplinary clinic where the patient is seen by the full oncology 

team, every hospital that treats breast cancer should have a weekly Tumor Board 

conference where cases are discussed between available specialists. 

As a general role, the primary treatment is surgery. Partial mastectomy plus 

radiation therapy is equivalent to modified radical mastectomy for primary breast 

cancer. When partial mastectomy is performed, special attention should be made to 

obtain comfortably negative margins. Young women are at a higher risk of having 

local recurrences after long-term follow-up and should have continued long term 

follow-up. The treatment with mastectomy and reconstruction remains a viable 

option, particularly in younger women. 

Adjuvant therapy includes chemotherapy, targeted therapy with trastuzumab, 

and hormonal therapy. Guidelines are referenced below.42-43 Athracyclines and 

taxanes are the most commonly used drugs, either separately, or in sequence, or 

combination. Classical oral CMF remains a viable option. Attention to resources 

and health care planning in countries with limited resources are presented by 

Breast Health Global Initiative (BHGI) .44 

Locally advanced breast cancer is treated with neoadjuvant therapy, preferably 

and more clearly called pre-operative therapy. Pre-operative therapy is usually 

anthracycline-based. 45 Taxanes improve breast conservation rates and increase 

complete pathological remissions46 Patients with less residual disease tend to 

have better survival.47 Higher rates of clinical and pathological remissions may 

be obtained with chemotherapy and targeted therapy in the presence of HER2 

positive tumors. Hormonal preoperative therapy gives good clinical responses 

produces but rarely produces complete pathological remissions and is useful in 

older postmenopausal patients. Preoperative therapy requires adequate radiological 

and pathological evaluations to be available.48 

Guidelines for the treatment of metastatic disease are referenced below. In general, 

hormonal therapy is indicated for hormone-receptor positive metastatic disease 

with bone and soft tissue metastases. Chemotherapy is used in patients with 

visceral metastases such as in the liver and lung. Chemotherapy is generally 

used when patients have aggressive and rapidly progressive disease particularly 

in young patients. Ovarian ablation (surgical, or by radiation therapy, or more the 

more costly ovarian suppression by LHRH analogs is preferred in premenopausal 

women. Tamoxifen with ovarian ablation is better than tamoxifen alone. Tamoxifen 

is effective anti-estrogenic therapy also in post-menopausal patients. Aromatase 

Inhibitors, particularly letrozole has been shown to be more effective than 

tamoxifen. Attention to resources and availability of therapy is important in 

countries with limited resources and has started to gain attention in major medical 

conferences and journals as referenced below.48 

Targeted therapy with anti-HER2 agent trastuzumab has become an essential 

component of the treatment of CerbB2 (HER2/neu) positive disease. Trastuzumab 

may be combined with hormonal therapy (TanDEM trial) or chemotherapy 

particularly docetaxel, paclitaxel and vinorelbine. More recently, lapatinib, a 

dual anti-Her2 and tyrosine kinase inhibitor has been reported to be beneficial in 

trastuzumab-resistant patients and also upfront when effectively combined with 

hormonal therapy in combination with letrozole and lapatinib in breast cancer 

(Abstract #81/ 31st Annual San Antonio Breast Cancer Symposium, 2008). 

Modern treatment of breast cancer should include research and clinical trials to 

find better answers for many questions. Modern chemotherapy, targeted therapy, 

and new hormonal therapy require more research and participation in international 

phase III trials. The medical community in the Arab World is urged to establish 

nationwide and hospital computerized databases and publish its findings and 

its research in peer-reviewed scientific journals. Multidisciplinary approach to 

cancer management is currently practiced only in few major medical centers and 

should become standard practice in all hospitals that treat breast cancer. More 

cooperation between various specialists to improve care of breast cancer patients 

is direly-needed. A few cancer centers exist in Arab countries and many more are 

needed. Encouragement and funding of cancer research should become a priority 

in Arab countries. Readers are referred to Breast Health Global Intitiative BHGI 

resource-oriented guidelines published in the October 2008 issue of Cancer.48 

7. Prevention Through Risk Factor Modification 

It is clear that modern therapy for breast cancer has become more effective and 

more expensive. Prevention and early detection may save major parts of costs 

of adjuvant and metastatic disease therapy. Several strategies are available for 

reducing breast cancer risk in countries with lower resources, but few of them 

have completed rigorous testing in clinical trials.28 Strategies to increase the 

prevalence and length of lactation may reduce risk for breast cancer in mothers in 

addition to providing nutrition benefits for infants and small children. Increased 

adiposity, a sedentary lifestyle and moderate to high levels of alcohol use are 

associated with increased risk of breast cancer. The evidence of a role for specific 

dietary components is less clear. For individual women, counselling should include 

increasing physical activity and balancing energy such that weight remains stable 

over a lifetime and, preferably, with the body mass index remaining


Table 3: Prevention Through Risk Factor Modification 

Risk Factors Suggested Modification 

Breast feeding To prolong lactation ≥ 1 ½ years 

at least as many studies proved its 

beneficial protection. 

Lifestyle and diet Increase mobilization, avoid weigh 

gain specially after menopause, 

regular exercise. 

Smoking, alcohol Avoid smoking and alcohol. 

Hormone Replacement Therapy 

(HRT) 

Should not be given routinely to 

postmenopausal women. Should 

not be dispensed from pharmacies 

without prescription. 

8. Early Detection: Experience in Arab Countries 

In the majority of Arab countries, screening is not standard of care. However, few 

promising screening initiatives emerged recently in some countries. The Cairo 

Breast Cancer Screening Trial was reported in 2005. It included training nurses 

and social workers to provide lectures and demonstarations, breast examinations, 

and referring women with suspicious findings to a nearby Italian Hospital in 

Cairo. More early breast cancer cases and less mastectomies were reported by 

the investigators.39 Another major effort is being conducted with the Ministry 

of Health. 

8.1. Early Detection: Experience in Saudi Arabia 

In Saudi Arabia, several studies were done evaluating the perceptions of women 

regarding breast cancer screening. In addition to physician barriers to breast 

cancer screening, studies identified the following factors: lack of knowledge about 

mammography as it is the standard screening test, breast cancer risk factors and 

lack of knowledge of practice BSE.51, 52 

The study that targeted primary health care physician concluded that the main 

barriers to breast cancer screening were: the unavailability of a national screening 

program, lack of women cooperation and compliance, lack of allocated time by 

physicians, and lack of knowledge regarding screening recommendations. 53 

Recently, two screening programs were developed; one in Al-Qaseem region where 

investigators developed a program for early detection of breast cancer that included 

staffing by trained nurses, pathologists and radiologist and target 75,000 female 

ages 35-60 in the region. The program has five permanent screening centers and 

a mobile one. So far, they completed three years since they started but no official 

results, for their findings are available yet (Alhabdan, personal communication). 

The second screening center is the Abdul-Lateef Center for Screening in the capital 

city of Riyadh, which opened in October 2007. The center is equipped with a digital 

mammogram machine, an ultrasound and two radiologists for double reading of 

mammographies, in addition to general practitioner and health educator who will 

interview the women and provide them with the screening questionnaires. For 

women with average risk factors using Gail Model questionnaires, a mammogram 

will be done based on BIRADS System (taken from http:/www.imaginis.com/ 

breasthealth/acrbi.asp). After a screening mammography is generated, the women 

are contacted. Those who need further evaluation are sent to King Abdulaziz 

Medical City or King Fahad Medical City in Riyadh.. So far, over 1,800 females 

were screened and 22 women were confirmed to have malignancies. A few of 

those malignancies were ductal carcinoma insitu (DCIS) and Stage 1 disease. 

Investigators are encouraged and women are re-assured that we see early breast 

cancer rather than the usual advanced disease. Challenges facing the investigators 

include refusal of many women to do further investigations, and even some 

women refused to have treatment. Those issues highlight the importance of breast 

health education for the general population. Results of this program are accepted 

presentation in ASCO 2009. 

8.2 Experience from Lebanon 

In addition to general public awareness campaigns, there is a systemic campaign 

that started in 2003, in collaboration with the Ministry of Health, Lebanese Society 

of Medical Oncology, Non Governmental Organization Faire Face (Facing Cancer), 

and pharmaceutical company Hoffman-La Roche. Every October, the campaign 

runs billboard ads, TV ads, intense TV and newspaper and magazine interviews 

about breast cancer screening and education. The campaign recently evolved into 

getting offers for low-cost mammography offered once a year for women over 

40. The Campaign and Ministry of Health offer classes and guidelines for quality 

mammography for participating centers. In parallel to the campaigns, there has 

been a noticeable increase in mammography-detected cancers, small tumors, and 

less total mastectomies being performed at major institutions.42 A National Breast 

Cancer Task Force has evolved to plan further actions. 

8.3. Breast Cancer Screening Recommendations 

The recommendation of breast cancer early detection/screening in average risk 

and high risk women are depicted in Tables 4 and 5. These guidelines should be 

followed in the Arab countries until future relevant evidences prove the need to 

modify these guidelines. 

Table 4: American Cancer Society (ACS) and National Comprehensive Cancer 

Network (NCCN) Recommendations for the Early Detection of Breast Cancer 

in Average-Risk Asymptomatic People 

Population Test or 

Procedure 

Frequency 

Women, aged Breast self- Beginning in their early 20s, women 

≥20 years but examination should be told about the benefits and 

40 years 

Clinical breast 

examination 

(CBE) 

Mammography Not recommended 

Breast self- Optional 

examination 

(BSE) 

Clinical breast Annually 

examination 

(CBE) 

Mammography** Annually 

Recommended that CBE be part of a 

periodic health examination, preferably 

at least every 3 years. 


* The ACS no longer recommends monthly (BSE) and women should be 

informed about the potential benefits, limitations and harms (the possibility of 

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Population Test or Procedure Frequency 

cure and care. 2007. www.who.int/cancer/en 

Prior thoracic radiation 

therapy (RT) for age 

Breast self-examination 

(BSE)* 

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4. Women’s News 10/05/06 U.S. Groups Join Saudi Breast Cancer Effort 

5. Laura Bush in Saudi Arabia to Promote Breast Cancer Awareness. Wikinews’ 


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20. Wang J, Constantine JP, et al. N. Lower-category benign breast disease and 

the risk of invasive breast cancer. J Natl Cancer Inst 2004; 96:616-20 

21. Vogel VG. Atypia in the assessment of cancer risk: Implication for management 

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breast cancer. J Natl Cancer Inst 2003;95:1079-85 

23. Velie E, Kuldorff M, et al. Dietary fat subtypes and breast cancer in 

postmenopausal women: A prospective cohort study. J Natl Cancer Inst 2000, 

92:833-9 

24. Key T, Appleby PN, et al. Body mass index, serum sex hormones and breast 

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25. Harvie M, Howell A, et al. Association of gain and loss of weight before and 

after menopause with risk of post menopausal of breast cancer in Iowa Women’s 

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27. El Saghir NS, Khalil MK, et al. Trends in epidemiology and management of 

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Int J Surg 2002 Aug; 5 (4):225-33 

28. Gulf Center for Cancer Registry (GCCR). 2004 

29. M. Lamyian, A. Hydrania, et. Al. Barriers to and factors facilitating breast 

cancer screening among Iranian Women : A qualitative study. Health Journal Vol 

13 No 5: Sept. – Oct. 2007 

30. Nasser Elkum, Said Dermime, et al. Being 40 or younger is an independent risk 

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BMC Cancer 2007, 7:222 doi:10.1186/1471-2407-7-222 

31. Nagi El Saghir, Muhieddine Seoud, et al. Effects of young age at presentation on 

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32. Thompson WD. Genetic epidemiology of breast cancer. Cancer 1994;74:279- 

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33. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast 

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advanced breast cancer: treatment guidelines with particular attention to low- and 

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2006; vol 6 Issue 5 


CANCER MAGNITUDE IN SHAM COUNTRIES 

Khatib S. 1 , Al-Tarawneh M. 2 

(1) King Hussein Institute for Biotechnology and Cancer 

(2) Ministry of Health, Jordan 

Corresponding Author: Dr. Sami Khatib 

Senior Assistant Director General, King Hussein Institute for Biotechnology and 

Cancer (KHIBC), Amman, Jordan 

E-mail: skhatib@khibc.jo 

Objective 

This study was designed to present and highlight some epidemiological 

characteristics of cancer in Sham countries 

Methodology 

Epidemiological data on cancer in Sham countries as in many Arab countries 

are limited. In this study we searched Pub Med, Medline, WHO, Globocan and 

MECC publications, national cancer registries and abstracts where it is available. 

We analyzed available data on some epidemiological characteristics of cancer in 

Sham countries and compared it to other Arab countries (KSA, Oman, Kuwait, 

Egypt, Tunisia). 

Results 

It was found that cancer of all sites is more predominant in females with a male 

to female ratio less than 1 in all Sham countries except in Syria where it is the 

reverse. The median age at diagnosis of cancer in all Sham countries is within the 

range of 52-56 years. The age standardized rates for males (ASR per 100,000 male 

populations) in Sham countries are as follow (Jordan, Lebanon, Syria, Palestinewest 

bank, 113, 179, 166, 128, respectively), it is higher than that in KSA, Oman, 

but less than that in Egypt. The same was found for the ASR in females. The five 

leading cancers among men in Sham Countries are: Jordan; colo-rectal (11.4%) 

leukemia (11.2%) lung (10.7%) urinary bladder (8.1%) prostate (7.6%) Lebanon 

as follow: Prostate (16.5%) urinary bladder (16%) lung (15%) colorectal (7.9%) 

and lymphoma 4.8%. In Palestine-West bank as follow: lung (12.4%) lymphoma 

(9.6%) colorectal (9.2%) prostate (9.1%) and urinary bladder (8.4%). In Syria, 

the five leading cancers among men as follow Lung (11.8%), urinary bladder 

(9.8%), Colorectal (9.6%), prostate (9.3%), N.H. Lymphoma (8.1%). Whereas 

among women the 1st rank cancer in all Sham countries is the breast cancer with 

relative frequency as follow (Jordan, Lebanon, Palestine, 34.8%, 40.2%, 27.2%, 

respectively) except in Syria where the uterus cancer is the 1st (32.6 %). The 

2nd is colorectal (Jordan, Lebanon, Palestine, Syria, 9%, 7.6%, 27.6%, 9.4%, 

respectively). ASR for colo-rectal cancer was found to be similar for all Sham 

countries and approximately the same for men and women (7 for men and 6 for 

women, also it’s similar to ASR in KSA, Oman Egypt and Tunisia (except Lebanon 

15.5 for men, 14.2 for women per 100,000 populations its similar to that found in 

Kuwait. ASR for lung cancer is 4 times higher in males than females in all Sham 

countries. The ASR for bladder cancer is higher in males than females in all Sham 

countries with a range from 1.3-4.8). The other cancers (stomach, lymphoma, 

leukemia); the ASR is higher in males than females. The ASR for prostate cancer 

was found to be similar in all Sham countries and the Arab countries included in 

the analyzes. The highest ASR for breast cancer was found in Lebanese females 

(69.2/100.000) meanwhile the lowest rate was found in Syria (31.2/100.000). 

Conclusions and recommendations 

Cancer incidence is on the rise in all Sham countries as in other Arab countries 

where incidence rates for both men and women is increasing. Comprehensive 

cancer control programs are highly needed. Inter-countries cooperation and 

collaboration is recommended. 



THE ROLE OF MRI ON CANCER DETECTION AND MANAGEMENT: 

THE SAUDI ARABIAN EXPERIENCE 

Aldabbagh A. 1 

(1) King Abdulaziz University Hospital, Jeddah, KSA 

Corresponding Author: Prof. Dr. Asma Aldabbagh 

Professor and Consultant in Radiology, Radiology Department 

Faculty of Medicine & Allied Sciences, King Abdulaziz University Hospital 

P.O. Box 80215, Jeddah 21589, Kingdom of Saudi Arabia 

Introduction 

MRI is increasingly being used as a problem solving tool; Examination timing, 

indications, and technique are critical to its success. It is particularly useful in 

mammographically-dense breasts, patients presenting with abnormal axillary 

nodes, the post-operated breast and to monitor neoadjuvant therapy response. It 

has also been recommended for screening high risk patients. 

Disease Epidemiology 

Breast Cancer in Saudi Arabia is the most common cancer in women. National 

screening is as yet not implemented. Most women usually come because of 

symptoms. Many of the cancers discovered are at an advanced stage. 

Screening Methods Overview 

Although mammography remains the primary imaging modality for the detection 

and evaluation of breast cancer, additional imaging is usually required to further 

stage the disease so that preoperative or other management strategies are planned. 

MRI is superior to other modalities in the detection of occult disease in the same or 

contralateral breast. MRI is also superior than other breast imaging modalities in the 

evaluation of the post operative breasts, monitoring neoadjuvant chemotherapeutic 

response and in the assessment of high risk patients. 

In our hospital, 1226 patients had breast MRI examinations. 406 patients were 

thought to have malignant lesions based on MRI findings. 298 cases were 

histopathologically proven malignancies. Of the proven malignant cases, 28 

patients gave a family history of breast cancer. 71 patients continued their 

investigations elsewhere and histopathology results were not available. 35 cases 

were false positive. Only 2 cases were false negative. Breast cancer recurrence 

was diagnosed by MRI in 42 patients, 8 of those were histopathologically negative 

for malignancy. Only a few patients were monitored by MRI during the course 

of their Neoadjuvant therapy. 

Outcome and Recommendations 

• Contrast-enhanced MRI has a high sensitivity and a high negative predictive 

value for the detection of invasive breast cancer. 

• It is superior to mammography and sonography for the detection of 

recurrence. 

• Breast MRI should be interpreted in conjunction with other breast imaging 

modalities. 

• Patients' history with dates of previous treatments should be given. 

• As with mammography, previous MRI studies availability is helpful. 

• It is also logical that lesions found only on MRI are biopsied under MRI 

guidance, a situation which is difficult to undertake in most hospitals if a 

dedicated breast MRI unit is not available. 

• MRI should be used to screen high risk patients. 

• MRI has made a significant impact on breast cancer detection and management 

in our practice. 

References 

1. Christiane K. Kuhl, Current Status of Breast MR Imaging. RSNA, 2007. 

2. Laura Liberman et al, Breast Lesions Detected on MR Imaging: Features and 

Positive Predictive Value, AJR 2002; 179:171-178. 

3. Elizabeth Morris, Laura Liberman, Breast MRI Diagnosis and Intervention. 

4. Constance D. et al. Cancer Yield of Mammography, MR, and US in High-Risk 

Women: Prospective Multi-Institution Breast Cancer Screening Study. Radiology 

2007;244:381-388. 

5. Ansgar Malich et al, Potential MRI Interpretation Model: Differentiation of 

Benign from Malignant Breast Masses. AJR 2005; 185:964–970 


ONCOLOGIST PERSPECTIVE ON TOBACCO CONTROL: 

HISTORICAL VIEW AND PRACTICAL GUIDELINES 

Mushabbab Asiri MD FFR RCSI FRCPC 1 , Abdullah Al Amro MD FRCPC 3 , 

Sulaiman Al Sobai 3 and Abdul Rahman Jazieh, MD, MPH 4 

(1) Department of Oncology Riyadh Military Hospital and Prince Sultan 

Haematology and Oncology Center King Fahad Medical City Riyadh, Saudi 

Arabia, Saudi Cancer Society and Prince Sultan Haematology and Oncology 

Center King Fahad Medical City Riyadh, Saudi Arabia, 

(3) Saudi Anti Smoking Organization, Riyadh, Saudi Arabia 

(4) Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia 

Corresponding Author: Mushabbab Asiri 

Director Department of Oncology Riyadh Military Hospital, PO BOX 295868, 

Riyadh 11351, Saudi Arabia 

E mail: mushabbabasiri@gmail.com / maasiri@rmh.med.sa 

Abstract 

Background: Tobacco use is a major risk factor for multiple health problems 

including many types of cancer. It is estimated that about third of the cancer cases 

are attributed to tobacco exposure. 

Methods: Review of the literature about tobacco use and its associated risk in 

cancer development was conducted and summarized in addition to the local 

experience in tobacco control initiatives and program. 

Results: Tobacco is a rising healthcare concern in the region that will lead to 

significant increase in cancer cases. Various smoking cessation program and 

interventions are identified in addition to potential roles of physician in combating 

these deadly habits. Recommendations to the practicing health provider in the 

region were suggested. Various recommendations about physician roles in this 

issue were also reviewed. 

Conclusion: In spite of its known risk to health, tobacco use remains a growing 

health concerns. Individual health care providers, organizations, and government 

need to carry well orchestrated efforts to minimize tobacco associated risks. 

Introduction and History 

Smoking is a practice where the substance such tobacco is burned and its smoke 

inhaled, the composition releases the active ingredients such as nicotine making 

it available for absorption through the lungs. 

Smoking evolved in association with a ritual ceremony 7000 years ago originated 

in Peruvian and Ecuadorian Andes and was found in several ancient civilizations 

such as Indian, Chinese, Babylonians, Greece, Shamans, Maya and Aztec tribes 

in South America (1) 

Hashishah (cannabis) smoking was known in the Middle East for several hundred 

years before the arrival of tobacco. 

Using water pipe called (hookah) in Urdu language was common practice in the 

Middle East and the water pipe (Shishah, Argelah) was a major part of wedding 

gifts in several parts of Middle East especially Iran and Turkey. This habit has 

spread to other areas during Othman empire.(2,3) 

The European adopted the smoking habits subsequent to colonization of the 

Americas in the 16th century. Jean Nicot, a French diplomat, brought tobacco 

plant from Portugal to France and introduce it to the high class family of France 

whom call it Nicotiana plant after his name in 1560. From his name, the word 

nicotine was derived, tobacco smoking spread from France to England and to 

the rest of Europe.(4) 

Inhalation of substances during the inspiration will deliver the active substances in 

the smoked materials into the circulation very effectively because the lung contains 

millions of alveoli and this route of drug administration is commonly used in the 

treatment of bronchial asthma and in anesthesia that it is fast and effective but 

unfortunately this route had been abused by recreation drug abusers. 

Tobacco is plant that its leaves processed for the production of smoked tobacco that 

is used for chewing or sniffing of cigarettes, cigar, pipe and hookah (Sheeshah). 

Modern cigarette made of blended shredded tobacco leaf and tobacco dust processed 

in a steamer refining factories stuffed in side paper like material reconstituted from 

recycled of tobacco fines. It contains in addition to nicotine several additives 

such as ammonium, polystyrene foam, glycerol, cocoa, licorice, microorganism 

(bacteria and fungi from soil), pesticides, carbon dioxide and sugar. 

Nicotine in tobacco stimulates chemical reaction in the brain that leads to light 

feeling of pleasure being similar to natural body substances such as endorphin 

and dopamine’s, contrary to cocaine and heroin which induce deep temporary 

feeling of pleasure.(5) 

Epidemiology of tobacco 

More than one billion people smoke tobacco globally, smoking related diseases 

killed one in 10 adult, every 8 seconds someone dies from tobacco use. 

15 billion cigarettes are sold daily that make 10 million cigarettes are sold every 

minute. Smoking habits is very common all over the world; in Cambodia, China, 

Korea 67% of men smoke, in Philippines 60% of men smoke, in Japan 51% of 

men smoke, half of all Malaysian are smokers.(6) 

Word Health Organization estimated tobacco smoking stratified by gender as 

depicted in Table 1. 

Table 1: Smoking Prevalence by Gender (2000, World Health Organization 

estimates) (6) 

Percent Smoking 

REGION MEN WOMEN 

Africa 29 4 

United States 35 22 

Eastern Mediterranean 35 4 

Europe 46 26 

Southeast Asia 44 4 

Western Pacific 60 8 

In the United States, smoking rates have dropped from 42% to 20.8% between 

1965 to 2006.(7) 

Unfortunately, there are no authenticating statistics about tobacco smoking in the 

Arab world apart from estimated statistics published by a different anti smoking 

charity organization. United State Census Bureau, International Data Base, 2004, 

present one of the most valuable data that gave Extrapolated Statistics in absence 

of solid data in the Arab World about tobacco smoking Table 2.(8) 



Table 2: Extrapolated Statistics of smoking in some Arab countries (8) 

Country Estimated Smoker 

Egypt 16,974,184 

Gaza strip - West Bank 295,472-515,398 

Iraq 5,658,555 

Jordan 1,251,298 

Kuwait 503,433 

Lebanon 842,319 

Libya 1,255,843 

Saudi Arabia 5,752,493 

Sudan 8,730,039 

Syria 4,017,762 

United Arab Emirates 562,833 

Yemen 4,465,545 

The following data was collected from 5 different sources could give impression 

about the magnitude of smoking in the Islamic world (Table 3) 

Country Population 

Million 

Table 3 : Smoking facts and figures in some Muslim countries 

Adult >15% Youth 

Prevalance of 

tobacco use 

Adult 

Prevalance 

of tobacco 

smoking 

males % 

Adult 

Prevalance 


smoking 

females % 

Adult 

Prevalance 


smoking % 

Cigarette 

consumption 

(million sticks) 

Estimation 

Albania 3.6 77 NA 39.6 3.9 40.5 NA 2003 

Algeria 34 75 13.8 29.9 NA 29.9 21500 2003 

Bangladesh 141 64.5 5.8 48.6 25.4 36.8 23000 2004 

Bahrain 0.727 74.1 19.9 26.2 2.7 26.1 796 2001 

Egypt 83 69.7 12.6 59.3 2.7 29.9 61000 2005 

Indonesia 240 72 13.5 63.2 4.5 34.5 185000 2006 

Iran 66 79 13 24.1 4.3 14.2 48000 2005 

Iraq 29 62 20.3 25.7 1.9 25.8 NA 2006 

Jordan 6.3 69 17.2 61.7 7.9 62.7 NA 2002 

Kuwait 2.6 74 20.9 30 1.5 15.6 3216 2004 

Lebanon 4.01 74 28 29 6.9 29.1 6390 2002 

Libya 6.3 67 11.1 55.5 2.5 NA 5560 2003 

Malaysia 26 69 NA 43 1.6 26.4 22000 2003 

Morocco 35 70 14.5 29.5 0.3 29.5 14700 2006 

Oman 3.4 57 15.2 24.8 1 24.7 1776 2000 

Pakistan 176 63 10.1 32.4 5.7 19.1 59000 2003 

Palastine 3.9 56 39.9 NA NA 35.4 NA 2005 

Qatar 0.83 79 17.9 37 0.5 18.8 864 2005 

Saudi Arabia 22 62 15.9 25.6 3.2 25.6 14431 2006 

Sudan 41 60 14 23.5 1.5 12.9 1475 2003 

Syria 20 64 35.5 50.6 9.9 44 10270 1999 

Tunisia 10 78 18.3 61.9 7.7 34.8 11498 2004 

Turkey 79 73 8.4 52 17.3 34.6 125000 2003 

UAE 4.7 80 24.9 27.2 2.4 26.1 3627 2003 

Yemen 24 54 21 77 29 44.5 5040 2006 

22 > Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info 

Year of 

survey

Sources : 

CIA the 2008 world fact book 40 

WHO - Global Youth Tobacco Survey (GYTS) 41 

Country & Regional Profiles and Economics of Tobacco Briefs 42 

WHO Statistical Information System (WHOSIS) 43 

Nation Master 44 

In Saudi Arabia there are no national data about smoking habits apart from dozens 

of studies describing smoking practice in universities and schools or smoking habits 

in health workers which might not describe the smoking problem in Saudi Arabia, 

One of the studies based on questionnaires distributed among primary care clinic 

attendants that showed of 634 subjects, 34.4% (218) were current smokers, 16.4% 

(104) were ex-smokers, and 49.2% (312) were nonsmokers (10) 

Saudi anti smoking charity organization reported that six million smoker smoke 

15,000,000 000 cigarette annually costing more than one 1,000,000,000 Saudi 

Riyal based on import /export customs report, 23,000 person die annually as a 

direct result of cigarette smoking which means 63 person die on daily basis. Saudi 

Cancer Registry estimates that one third of cancer patient in Saudi Arabia has 

smoking as causative agent.(11) 

Smoking Risk 

(Have you not reason then to be ashamed, and to forbeare this filthie noveltie, so 

basely grounded, so foolishly received and so grossly mistaken in the right use 

thereof? In your abuse thereof sinning against God, harming your selves both in 

persons and goods, and raking also thereby the marks and notes of vanity upon you: 

by the custom thereof making your selves to be wondered at by all foreign civil 

nations, and by all strangers that come among you, to be scorned and contemned. 

A custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous 

to the lungs, and in the black stinking fume thereof, nearest resembling the horrible 

Stigian smoke of the pit that is bottomless). 

The above quotation had been written more than 400 years ago by King James I 

of England in counter blasé to tobacco treaties in 1604. (12, 13) 

Tobacco smoking is one of the most common preventable health hazards that kill 

millions of peoples every year more than death caused by AIDS, suicide, murder, 

fires, accidental poisoning and traffic accidents combined. 

There are hundreds of studies correlate tobacco smokings to certain diseases 

which circulating around three major health problems: cardiovascular diseases, 

respiratory system diseases and cancer. 

The small fine particles that sneak through alveolar wall and exert their effects 

on the heart and blood vessels. Carbon Monoxide (CO) in tobacco impairs the 

hemoglobin ability to carry oxygen and the heart compensates for the low oxygen 

content by pumping more blood which is evident by increasing the heart rate by 

at least 30 % during smoking.(12) 

Smoking increases the platelet production, blood pressure (13), cholesterol and 

fibrinogen which together increase the risk of thrombi formation, arteriosclerosis 

and ischemia which could be fatal. 

Chronic obstructive pulmonary disease (COPD), defined as the ratio of forced 

expiratory volume in 1 second (FEV1) to the forced vital capacity (FVC) being < 

0.7 and the FEV1 being 50-80% of the expected value, caused mainly by smoking 

and it is a common cause of death in smokers.(14) 

Burning of organic compounds that occur during smoking releases several 

carcinogenic agents that damage the DNA causing several mutations. These 

agents contain hydrocarbons and acrolein which are potent carcinogens and 

as a result of that, smoking is linked to 15 different cancers and causes 30% of 

cancer related death. 

Cancer of lips, oral cavity, larynx, pharynx, lung, pleura, esophagus, breast, 

stomach, kidney, pancreas, colon, cervix, acute myeloid leukemia and cancer of 

bladder are well linked to tobacco smoking. 

Tobacco smoking contributes to other diseases such as cataracts, gum disease, 

aortic aneurism, and sudden infant death. It worsens diabetes complications and 

delay the wound healing.(15) 

Second Hand Smoking 

Many of 3800 compounds in tobacco smoke are known carcinogens. These 

compounds unfortunately do not just affect the smoker only but everyone around 

him who inhale this smoke. 

The passive smoker exposed to the side stream smoke emitted from the burning 

tip of the cigarette. Side stream smoke is hazardous because it contains high 

concentrations of ammonia, benzene, nicotine, carbon monoxide, and many 

carcinogens. Nonsmokers chronically exposed to side stream are believed to 

assume health risks similar to those of a light smoker. Children of parents who 

smoke have more respiratory infections, more hospitalizations for bronchitis and 

pneumonia, and a smaller rate of increase in lung function compared to children 

of parents who do not smoke, particularly during the first year of life. (16) 

Secondhand smoking or passive smoking or what is called “environmental tobacco 

exposure (ETS)” can cause the same problems as direct smoking. It is well known 

that non-smokers exposed to cigarette smoke in the workplace have an increased 

lung cancer risk that shown by the meta-analyses published by a Sasco AJ et al 

where lifelong non smokers with partners who smoke at home have a 20 to 30% 

greater risk of lung cancer than non-smokers who live with non-smokers.(17) 

Boyl P et al published data about non-smokers exposed to cigarette smoke in 

the workplace that showed increased lung cancer risk of 16 to 19% among non 

smokers. (18) 

Having a spouse who currently smokes was associated with an increased risk 

of first stroke among never-smokers (hazard ratio=1.42, 95% CI=1.05, 1.93) 

and former smokers (hazard ratio=1.72, 95% CI=1.33, 2.22). Former smokers 

married to current smokers had a stroke risk similar to respondents who themselves 

smoked.(19) 

A recent paper from China estimated the burden of diseases in adults from passive 

tobacco smoking for two major diseases: lung cancer and ischemic heart disease 

(IHD). It showed that passive smoking caused more than 22,000 lung cancer 

deaths in 2002 and when the toll of disability is added to that of mortality, passive 

smoking was responsible for the loss of nearly 230,000 years of healthy life from 

lung cancer. They estimated approximately 33,800 IHD deaths could be attributable 

to passive smoking in China in 2002. Passive smoking is also responsible for the 

loss of more than one quarter of a million years of healthy life from IHD.(20) 



These data encouraged the health authority in many countries to implement 

smoking ban policy 

Smoking Cessation Benefits 

Smoking cessation is associated with important benefits such as improved lung 

function and a better general health and performance status. It might lead to longer 

survival and reduced complications of radiation therapy in lung cancer patient.(21) 

Costa F. et al tried to answer the question whether smoking cessation is worthwhile 

in patients with lung cancer as a common theme among patients that it “may be 

it is not worthwhile” given the bad prognosis. However, Costa found that: “it is 

worthwhile”.(22) 

(Smoking can influence lung cancer in several ways such as promoting relapse 

and the development of other types of cancer, smoking increases the growth and 

aggressiveness of tumors, nicotine interacts with the non-neuronal nicotinicacetylcholine 

receptors, leading to an increase in VGEF, nitric oxide and 

prostacyclin, inducing an increase in tumor growth, complicating surgery because 

smoking increases the surgical risk and postoperative complications, slowers wound 

healing and reduces survival after surgery, interfering with radiotherapy hence the 

hypoxia induced by carbon monoxide may be responsible for a worse response to 

radiotherapy. Smoking also increases the risk of radiation pneumonitis by promoting 

inflammation and diminishing the mucociliary clearance. As for chemotherapy, 

smoking interferes with cytochrome P450, accelerating the metabolism of several 

drugs including some chemotherapeutic agents (taxans, vinorelbine, etoposide, 

doxorubicin, gefitinib), diminishing their serum levels and their efficacy. It seems 

by this group of evidence that smoking cessation in lung cancer patients is in fact 

worthwhile.(22) 

Smoking cessation was associated with a decrease in the risks of ischemic stroke, 

subarachnoid hemorrhage, and MI.(23) 

Quitting smoking is associated with a substantial reduction in risk of all-cause 

mortality among patients with CHD, 36% reduction in crude relative risk (RR) 

of mortality for patients with CHD who quit compared with those who continued 

smoking.This risk reduction appears to be consistent regardless of age, sex, index 

cardiac event, country, and year of study commencement.(24) 

Smoking reduction was associated with a significant decrease in the risk of lung 

cancer. (25) 

Song YM, et al reported recently that smoking cessation substantially reduces the 

risk of smoking-related cancers of the lung, larynx, esophagus, and pancreas, and 

is the most effective method for reducing the risk of cancer among smokers.(25), 

Oral health usually improved after two weeks of tobacco cessation with resolution 

of smoking related oral lesion with overall improvement of periodontal and oral 

health.(26) 

Smoking Bans and Public Policies 

Smoking ban aims at protecting people from the harmful effects of second-hand 

smoke. Smoking ban policy is important tools in lowering smoking rates and 

promoting public health in addition lowering health service cost and improves 

morale and productivity and lower the overall cost of labor in a community. 

Effective tobacco control policies include law issuing, bans/restrictions on smoking 

in public areas and workplaces, increasing taxes on tobacco products, bans on 

advertising of tobacco products, land warning labels on cigarette boxes. 

The World Health Organization had published several policies and laws that helps 

health authority to implement cigarette smoking ban that helps many country to 

control the smoking habit and smoking becomes more difficult. 

Admissions for heart attacks dropped by 27% in Colorado after 18 months of 

implementation. Similar results were seen in Ireland, Scotland, UK and Sweden. 

These results support the smoking ban fans. 

The European Union (EU) has been active in tobacco control policy since 1985 

when the Milan Council announced its intention to establish a Europe Against 

Cancer (EAC) Programme. Shortly after the establishment of the EAC, first 

action plan the European Commission presented its first legislative proposals on 

tobacco control. Three of these proposals on labeling and maximum tar yields 

became Directives by 1992. The fourth on tobacco advertising finally became law 

in 1998 and is currently being transposed into national law in the 15 EU Member 

States. In 1996 the Commission published a Communication on the future of EU 

tobacco control and in 1999 at the 2nd European Conference on Tobacco and 

Health, the Social Affairs Commissioner announced his intention to bring forward 

further legislative proposals to amend an consolidate existing EU legislation in 

this sector. This article is intended to present an overview of EU tobacco control 

legislation from 1970 until 1998 and to look at future options post year 2000.(27) 

The smoking ban policies announced in Saudi Arabia on the year 1984 with 

Royal order banning smoking in all governmental buildings. Unfortunately 

the implementation of this policy was very weak and people continue smoking 

breaking the royal order. More than 43 charity organizations started to be active 

in smoking ban campaign that result of increasing the taxation of cigarettes twice 

in the last tow decade and community based clinics started to receive smokers 

seeking help for smoking cessation maneuvers. 

Impact of religious rulings (Fatwa) on smoking: 

The Qur'ān, The holy book of Islam, does not specifically prohibit or denounce 

smoking directly, but gives behavioral guidance: 

“Don't throw yourself into danger by your own hands...” (Surat Al-Bakara 2/195) 

“You may eat, drink, but not waste” (Surat Al-A‘râf 7/31) 

Several Fatwa issued in most of Islamic countries announcing that tobacco smoking 

is unlawful activity “Haram” (sin) based on understanding of The Holy Quran 

that stated in Surat Al Araf : (The Prophet) who will enjoin upon them the doing 

of what is right, forbid them the doing of what is wrong, make lawful to them 

the good things of life, prohibit for them the evil things, and lift from them their 

burdens and the shackles that were (previously) upon them.(28) 

Smoking spoils a person's acts of worship and reduces their rewards, it spoils the 

prayer, which is the pillar of Islam. Allah's Messenger said: Whoever eats garlic 

or onion let him avoid us and our masjid, and stay in his home. The angels are 

surely hurt by things that hurt the human beings.(29) 

But although claimed that Islamic rules helped in smoking cessation program 

especially in Ramadan where the smoking is unlawful during the day time during 

fasting but few medical studies addressed this issue. 


One study conducted in University of Southern California, Los Angeles, California, 

USA. examines religious and cultural influences with adolescents' susceptibility to 

smoking among Muslim Arab-American adolescents and found religious influence 

and perceived negative consequences of smoking were protective against ever 

smoking for both genders (OR=0.7, 95% CI=0.5-0.9; OR=0.8, 95% CI=0.7-0.9, 

respectively). (30) 

Egyptian Smoking Prevention Research Institute conducted a survey in a rural 

village and two nearby schools in Qalyubia Governorate to assess the knowledge 

about religious ruling (Fatwa) and its impact on the quit attempts. The results 

showed that the majority of respondents (81 %) knew about the Fatwa on smoking. 

97.3% of all participants thought that smoking is a sin. This indicates a successful 

outreach program targeting mainly men through mosques. 

Radwan et al concluded that knowledge about the Fatwa on smoking or belief that 

smoking is a sin had no significant effect on quit attempts (31) but that definitely 

depends on personal believes and religious practice and obedience that varies 

from person to person and from society to other, 

In Pakistan, a study tried to see the effect of Islamic practice status of person and 

correlate that with their smoking habits to see the rule of Islam on prevention of 

smoking and they found out of the study group 325 (32.5%) were found to be 

indulged in different kinds of smoking and concluded that Islam has a positive 

effect on smoking prevention.(32) 

Lung cancer prevention programs 

Lung cancer prevention programs depend on smoking avoidance. It is well known 

that cigarette smoking causes lung cancer and therefore smoking avoidance should 

result in decreased mortality from primary lung cancer. 

Nicotine replacement therapies in a form of gum, batch, spray, lozenge help to 

some extent in smoking-cessation programs and same apply to antidepressant 

therapy. The choice of therapy should be individualized based on the patient 

experience, preference and the agent side effects. 

The available data indicate that the intervention didn’t work for heavy-smokers 

where the quit rates was not significantly improved but it had improved among 

light-to-moderate smokers. 

Chemoprevention trial did not show promising result and is not yet established 

in standard clinical practice. 

Lung cancer screening for heavy-smokers is not yet established as standard clinical 

practice because no major benefits of cancer screening in lowering the morbidity 

or mortality of lung cancer in most of published screening program data. 

Smoking cessation programs 

Nancy Rigotti had published a practical guidelines for smoking cessation depending 

on pharmacotherapy and counseling which are the two approaches showing good 

result. Each is effective by itself, but the two in combination achieve the highest 

rates of smoking cessation.(33) 

Counseling 

Counseling about smoking cessation can be delivered effectively in person or 

by telephone. Group or individual counseling is effective when it is provided 

by trained counselors and includes repeated contacts over a period of at least 

four weeks. The efficacy of this approach increases as the amount of time spent 

with the patient increases. Cognitive behavioral methods form the core of most 

counseling programs. Typically, smokers learn to identify smoking cues, then use 

cognitive and behavioral methods to break the link between the cues and smoking. 

They also learn strategies for coping with stress, managing symptoms of nicotine 

withdrawal, and once they quit, preventing relapse, such as anticipating tempting 

situations and rehearsing coping strategies. (33-35) 

Smoking-counseling strategies are also summarized in pamphlets and booklets, 

audiotapes, videotapes, and computer programs. Written self-help material has 

negligible efficacy when used alone but may augment other interventions. Self-help 

material is more effective when its content is tailored to an individual patient's 

specific concerns or readiness to change(33-35) 



Figure 1: The 5As Model for Smoking Cessation 

Ask 

All patients including 

adolescents about smoking 

status. 

Do you smoke? 

Advise 

to quit smoking 

to quit Assess smoking 

the interest to quit 

smoking Do you 

feel you want to quit? 

Y ES   

Assist 

Help the patient to quit smoking 

(STARR ) 

(Setting a quit date, 

Telling friend, 

Anticipate challenges, 

Remove tobacco from patient 

environment, 

Recommend pharmacotherapy 

Arrange 

follow-up visit immediately after 

quit date 

Figure 1: The 5As Model for Smoking Cessation 

NEXT VISIT 

No/Not Now 

No/Not now 

Relapsed 


No 

Figure 2: Sites of action of pharmacotherapy for smoking cessation. 



Table 4: Mechanism of action, common adverse effects, and efficacy in meta-analyses of pharmacotherapy’s of current or 

Pharmacotherapy Mechanism 

of action 

Nicotine patch Nicotine 

replacement 

therapy 

Nicotine gum Nicotine 

replacement 

therapy 

Nicotine lozenge Nicotine 

replacement 

therapy 

Nicotine inhaler Nicotine 

replacement 

therapy 

Nicotine nasal 

spray 

Nicotine 

replacement 

therapy 

future use for treating tobacco smoking dependence. 

Daily Dose Common adverse 

Effects 

14-25 mg , One patch daily 

for 4 weeks , decreased by 

7 mg every 2 weeks for 8 

weeks 

4-mg gum for 25 or more 

cigarettes per day and 

2-mg gum for less than 25 

cigarettes per day. 

Use should not exceed 24 

pieces per day 

4 mg for those who have 

their first cigarette within 

30 minutes of waking 

2 mg for those who have 

their first cigarette later 

than 30 minutes after 

waking. 

1 lozenge every 1 to 2 

hours for 6 weeks ; no 

fewer than 9 per day but no 

more than 20 per day. Use 

up to 12 weeks. 

1-2 doses per hour 

increasing as needed. 

Minimum recommended 

dosage is 8 doses per 

day; maximum is 40. 

(approximately 100 doses 

per bottle) 3 to 6 months 

with Gradual reduction 

One spray in each nostril 

(0.5 mg) 1-2 doses /hr , 

Max 40/day for 3-6 months 

with gradual reduction. 

skin irritation insomnia, 

vivid dreams 

Nausea, vomiting, 

headache, dizziness, 

cold sweat, pallor, 

and weakness are 

all symptoms of an 

overdose 

Burning taste 

Hiccups 

Gastrointestinal 

symptoms, nausea 

Temporomandibular 

tenderness 

Tachycardia 

Mouth pain 

Hiccups 

Coughing 

Heartburn 

Sore throat 

Headache 

Indigestion 

Nausea 

Insomnia 

Irregular heartbeat 






overdose. 

Nasal airway reactions 

Dyspepsia 






overdose. 

Dependency - 15- 

20% use longer than 

recommended; 5% use 

at a higher dose than 

recommended 

Nasal irritation, 

Sneezing ,cough, teary 

eyes 

Efficacy 

Almost twice as 

effective as placebo 

when used 6-14 weeks 

at a dose of 14-25 mg 

(Fiore et al., 2008).39 

Long-term abstinence 

rates are increased 

approximately 50% over 

placebo (Fiore et al., 

2008). .39 

The continuous 

abstinence rates at 

6 months compared 

to placebo are 

approximately double 

(24.2 vs. 14.4 for 2 mg 

dose and 23.6 vs. 10.2 

for 4 mg (Fiore et al, 

2008)39 

Long-term 

abstinence rates more 

approximately doubled 

when compared to 

placebo.39 

double the likelihood of 

long-term quitting than 

those on placebo (Fiore 

et al., 2008).39 


Incentives for Smoking Cessation 

In recent randomized clinical trial, K Volpp et al found that financial incentives for 

smoking cessation significantly increased the rates of smoking cessation among 

2 matching smoker working in the same company in US where they randomly 

assigned 878 employees of a multinational company based in the United States 

to receive information about smoking-cessation programs (442 employees) or to 

receive information about programs plus financial incentives (436 employees). 

The financial incentives were $100 for completion of a smoking-cessation 

program, $250 for cessation of smoking within 6 months after study enrollment, 

as confirmed by a biochemical test, and $400 for abstinence for an additional 6 

months after the initial cessation, as confirmed by a biochemical test. 

The incentive group had significantly higher rates of smoking cessation than did 

the information-only group 9 or 12 months after enrollment (14.7% vs. 5.0%, 

P


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THE USE OF MRI FOR THE EARLY DETECTION OF BREAST CANCER 

Comstock C. 1 

(1) University of California, San Diego, Ca, USA 

Corresponding Author: Dr. Christopher Comstock, MD 

Associate Clinical Professor of Radiology, Director of Breast Imaging 

University of California, San Diego, La Jolla, CA, United States of America 

Dynamic contrast enhanced MRI of the breast is not limited by breast density 

and has been shown to be extremely sensitive in the detection of invasive breast 

cancer. However, because of the variable sensitivity of MRI for ductal carcinoma 

in situ (DCIS), between 45% and 100%, MRI is currently not recommended as a 

replacement for screening mammography(1). A more recent single institution study 

suggests that MRI may have a higher sensitivity as compared to mammography 

for DCIS than previously thought, particularly for high-grade DCIS(2). The use 

of MRI in the general population has been limited by its moderate specificity, 

leading to false positives and unnecessary biopsies. Therefore, its use has been 

focused on studying patients in whom the yield from MRI is likely to be higher. 

Multiple studies have shown that MRI is a useful tool as an adjuvant to screening 

mammography in women at high risk for breast cancer(3-5). 

In April 2007 the American Cancer Society (ACS) published new guidelines for 

screening high-risk woman(6). Risk is greatest for women with genetic mutations 

including BRCA1, BRCA2, p53, Cowden’s, and those women who underwent 

radiation therapy for lymphoma at an early age. Methods for estimating risk 

based on medical and family history include the Gail, Claus, and BRCAPRO 

mathematical models. Women who have a 20-25% lifetime risk for breast cancer 

based on family history as calculated by any of the aforementioned models are 

also considered high risk and appropriate for annual MRI. Women whose benefit 

from screening MRI is considered questionable by the ACS due to insufficient data 

include; women with a personal history of breast cancer, prior biopsy yielding atypia 

or women with extremely dense breasts on mammography(6,7). The decision to 

perform screening MRI in these women should be made on a case by case basis. 

Table: Risk factors that place women at increased risk of breast cancer 

BRCA1 or BRCA2 mutation, or untested first degree relative of known 

carrier 

Chest radiation between age 10-30 for Hodgkin’s Lymphoma 

Lifetime risk of 20-25% as determine by statistical risk assessment models 

such as BRCAPRO or Gail based on personal and family history 

Other genetic mutations including p53 and Cowden 

References 

1. Bazzocchi M, Zuiani C, Panizza P, et al. Contrast-enhanced breast MRI in 

patients with suspicious microcalcifi cations on mammography: results of a 

multicenter trial. AJR Am J Roentgenol 2006; 186: 1723–32. 

2. Kuhl CK, Schrading S, Bieling HB, et al. MRI for diagnosis of pure ductal 

carcinoma in situ: a prospective observational study. Lancet. 2007 Aug 

11;370(9586):485-92. 

3. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and 

mammography for breast-cancer screening in women with a familial or genetic 

predisposition. N Engl J Med. 2004 Jul 29;351(5):427-37. 

4. Lehman CD, Blume JD, Weatherall P, et al. Screening women at high risk for 

breast cancer with mammography and magnetic resonance imaging. Cancer 

2005;103:1898–905. 

5. Kuhl CK, Schrading S, Leutner CC, et al. Mammography, breast ultrasound, 

and magnetic resonance imaging for surveillance of women at high familial 

risk for breast cancer. J Clin Oncol. 2005 Nov 20;23(33):8469-76. 

6. Port ER, Park A, Borgen PI, Morris E, Montgomery LL. Results of MRI 

screening for breast cancer in high-risk patients with LCIS and atypical 

hyperplasia. Ann Surg Oncol. 2007 Mar;14(3):1051-7. Epub 2007 Jan 7. 

7. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for 

breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 

2007 Mar-Apr;57(2):75-89. 



DIET, PHYSICAL ACTIVITY, AND OBESITY IN THE PREVENTION 

AND RECURRENCE OF BREAST CANCER: RELEVANCE TO SAUDI 

ARABIAN WOMEN 

Mc Tiernan, A. 

Corresponding Author: Anne McTiernan, MD, PhD 

Director, Prevention Center, Fred Hutchinson Cancer Research Center 

PO Box 19024, , M4-B874, Seattle, Washington, USA 98109 

E-mail: amctiern@fhcrc.org 

Abstract 

Objectives: Diet, physical activity, and overweight/obesity can alter risk of 

developing breast cancer and may affect prognosis among women who are 

diagnosed with breast cancer. This manuscript outlines lifestyle behavioral 

strategies that show promise in the prevention and treatment/rehabilitation of 

breast cancer. 

Methods: Literature was summarized regarding the following major lifestyle 

behaviors that are relevant to breast cancer etiology and control: physical activity, 

weight control, and diet. 

Results: Compared with sedentary women, the risk of developing breast cancer is 

30 – 40% lower for women who exercise at moderate to vigorous levels for 3 – 4 

hours per week. Women who are overweight or obese have a 30 – 50% increased 

risk for postmenopausal breast cancer development compared with normalweight 

women. In contrast, overweight and obesity decrease risk of breast cancer 

occurring during the premenopausal years. There is no evidence that any one dietary 

component is related to breast cancer risk, although recent evidence suggests that 

women with low vitamin D levels may be at increased risk. Breast cancer patients 

at any age have increased risk of poor survival if they are overweight, obese, or 

sedentary. One large randomized trial found that a low-fat dietary pattern improved 

disease-free survival in women with early stage breast cancer. 

Conclusions: To reduce breast cancer risk, and to improve prognosis in women 

with breast cancer, weight should be maintained at normal levels (body mass index 

< 25.0 kg/m2) by reducing calorie intake and increasing physical activity (at least 

150 minutes/week). The preferred dietary pattern for maintaining normal weight 

is low in fat, high in vegetables and fruits, and low in refined carbohydrates. A 

low-fat dietary pattern may improve prognosis in breast cancer patients. 

Introduction 

Diet, physical activity, and overweight/obesity can alter risk of developing breast 

cancer and may affect prognosis among women who are diagnosed with breast 

cancer. Globally, rates of breast cancer incidence vary widely by geographic area. 

Only a small part of these differences are due to genetic differences, few chemical 

or other carcinogen exposures have been linked to risk, and the remainder of cases 

are likely due to individual health and lifestyle behaviors.(1) Around the world, 

within-country changes over time in breast cancer incidence have been paralleled 

by significant lifestyle and health behavior changes.(2) Experimental animal 

studies provide confirmation of an observable effects of overweight/obesity, diet, 

and physical activity on breast biology.(1) 

The International Agency for Research on Cancer (IARC) estimates that 25% 

of breast cancer cases worldwide are due to overweight/obesity and a sedentary 

lifestyle.(1) Recently, an expert panel commissioned by the American Institute for 

Cancer Research and the World Cancer Research Fund estimated that recommended 

diets, together with maintenance of physical activity and appropriate BMI, can in 

time reduce breast cancer incidence.(3) (4) 

An American Cancer Society cohort study of 495,477 women followed for 16 years 

found that risk of breast cancer mortality increased significantly with increasing 

level of obesity; compared with women with a body mass index (BMI) under 25.0 

kg/m2, those with a BMI of 25 – 29.9 kg/m2, 30 – 34.9 kg/m2, 35 – 39.9 kg/m2, 

and >40 kg/m2 had a relative risk of breast cancer mortality of 1.34, 1.63, 1.7, and 

2.12, respectively.(5) Therefore, lifestyle changes to increase physical activity and 

reduce excess weight might be expected to have a major impact on breast cancer 

risk and mortality. In countries where routine mammogram or other screening is 

not generally available, it is even more important to promote lifestyle changes to 

reduce risk of breast cancer and to improve prognosis in women with breast cancer. 

This manuscript outlines lifestyle behavioral strategies that show promise in the 

prevention and treatment/rehabilitation of breast cancer. It covers the following 

major lifestyle behaviors that are relevant to breast cancer etiology and control: 

physical activity, weight control, and diet. While alcohol use has been consistently 

linked to increased risk for breast cancer (6) likely through its effects on estrogen 

metabolism, it is very unlikely to be consumed by Saudi women, and therefore 

alcohol use is not included in this manuscript. 

Lifestyle Factors and Breast Cancer Prevention 

Physical Activity 

There is a very large body of epidemiologic data on the association between 

exercise and breast cancer.(7) Over twenty published cohort studies (8-30) have 

investigated the association between physical activity and risk of breast cancer, 

of which most (8-31) showed evidence of a reduced risk for breast cancer in 

women who were classified at the highest vs. lowest levels of physical activity. 

The reduction in risk ranged from 10 to 70 percent for the most active women, 

and on average was 30 – 40% lower for women who exercised at moderate to 

vigorous levels for 3 – 4 hours per week. The definition of “most active” varied 

by study, and depended on the questions asked, the population studied, and the 

researchers’ choice of categories of amount of activity. 

In the United States’ Women’s Health Initiative Observational Study, we studied 

the association between physical activity and risk of postmenopausal breast cancer. 

(18) Exercise reduced the risk of all types of breast cancer regardless of receptor 

hormone status or stage of disease, although the numbers in some subgroups were 

too small to precisely determine risk estimates. The Women’s Health Initiative 

Observational Study is a cohort of more than 93,000 women from across the United 

States, including women from varying race and ethnic populations. Moderate 

activities such as walking were as protective against breast cancer as were vigorous 

activities such as jogging. The beneficial effect of exercise was most pronounced 

in women with body mass index less than 27 kg/m2. 

In a study of over 25,000 Norwegian women, decreasing risk for breast cancer 

with increasing levels of leisure time physical activity (p trend = .08), and 

physical activity at work (p trend = .004) was observed.(27) There have been two 

publications from the U.S. Nurses’ Health Study cohorts on the association between 

physical activity and risk of breast cancer: one study assessed recreational activity 

reported at just one point in time,(24) and the other assessed repeated measures 

of activity at several time points during follow-up.(23) While the former study 

observed no association between physical activity and risk for breast cancer, the 

latter found that women who engaged in an average of seven or more hours per 

week of physical activity had an 18 percent lower chance (95% confidence interval 


3% to 30%) of developing breast cancer compared with women who engaged in 

less than one hour per week of such activities. Activity other than leisure-time 

activity was not assessed, which may obscure physical activity effects, as there 

may be considerable effect of occupational activity in a population of nurses. 

Some cohort studies have estimated breast cancer risk according to participation in 

college sports, some studied occupational physical activity only, several examined 

recreational exercise only, and others assessed effects of both occupational and 

recreational physical activity. Methods of measuring physical activity differed 

between studies, ranging from simply asking subjects questions such as, “In your 

usual day, aside from recreation, how active are you?”, to a physician-administered 

questionnaire that ascertained how many hours per day a subject usually spent 

sleeping, resting, sedentary, or at slight, moderate, or heavy activities, to detailed 

question of current and history of regular participation in various sports and other 

recreational exercise activities at different life periods. Therefore, it is even more 

significant that such a high proportion of studies have found an association between 

increased physical activity and reduced risk for breast cancer. 

More than two dozen case-control studies have been published on the association 

between physical activity and risk of breast cancer,(7) of which more than three 

quarters support a reduced risk for breast cancer in women who were the most 

active compared with sedentary women. Reduction in risk ranged from 10% to 70%. 

Reduced risks associated with increased physical activity have been observed 

for both premenopausal and postmenopausal breast cancer. Data from around 

the world suggest that physical activity is associated with reduced risk for breast 

cancer in women of diverse races and ethnicities.(30, 32-36) 

It is not clear at what ages physical activity provides the most protection against 

breast cancer. In a small number of case-control studies,(37-39) lifetime leisure 

activity was ascertained, while in other studies, activity levels at adolescence and 

discrete adult periods were obtained. Some studies found a reduction in risk with 

increased physical activity in adolescence, while in other studies risk reduction 

was limited to adult physical activity. 

It is important in studying the association between physical activity and breast 

cancer to control for potentially confounding factors, to be sure that the association 

between physical activity and breast cancer is not due to extraneous factors. 

Most studies have controlled for potential confounding factors such as age, 

reproductive history, and body mass index, and some have also adjusted for 

patterns of dietary intake. Since body size and adiposity may lie in the causal 

pathway between physical activity and breast cancer risk, simple adjustment may 

not give a complete picture. Indeed, some investigators found that breast cancer 

risk reduction associated with level of physical activity was limited to the leanest 

women.(27, 39-41) Adjustment for dietary macronutrient intake or caloric intake 

did not confound the physical activity-breast cancer relationship in studies that 

assessed dietary patterns.(15, 27, 33, 41-44) 

Identifications of the mechanisms linking physical activity and cancer risk will help 

in determining optimum ages to exercise, and the dose, frequency, and intensity 

of physical activities needed to protect against breast cancer. 

Early menarche (before age 12), increased numbers of ovulatory cycles, late first 

birth or nulliparity, lack of lactation, late age at menopause, increased number of 

lifetime ovulatory cycles, increased interval between menarche and menopause, 

and high concentrations of endogenous sex hormones (estrogens, testosterone) 

have been found to increase risk of breast cancer from 20 percent to more 400 

percent.(45, 46) Several of these reproductive and hormonal factors are affected 

to some degree by physical activity. 

In observational studies, pre-teen and teenage girls participating in vigorous 

activities such as ballet dancing, gymnastics, and running have been noted to 

experience a high incidence of primary and secondary amenorrhea, delayed 

menarche, and more irregular cycles, compared with non-athlete girls.(47, 48) A 

cross-sectional study of 174 girls aged 14 – 17 years found that girls who expended 

600 or more kcal energy per week (comparable to two or more hours per week 

in activities such as aerobic exercise classes, swimming, jogging, or tennis) were 

two to three times more likely than less active girls to have anovulatory menstrual 

cycles.(49) 

Exercise during reproductive life has been shown to alter the concentrations of 

sex hormones in human intervention studies.(50, 51) A high intensity exercise 

intervention in 28 untrained college women with normal ovulation resulted in 

reversible abnormal luteal function in two-thirds and loss of luteinizing hormone 

surge in more than 50% of subjects.(51) The greatest menstrual changes were 

observed during the periods of most intense training, and in those women who 

had been randomized to a weight loss (vs. weight maintenance) group. It appears, 

therefore, that a low body weight in addition to increased exercise is required to 

reduce ovulation. Thus, intense prolonged exercise or caloric restriction, or some 

combination of these, may be required. 

Postmenopausal women produce estrogen through the peripheral conversion (mainly 

in fat cells) of adrenal androgens to estrogens.(52) In postmenopausal women, 

increased physical activity is associated with decreased serum concentrations 

of estradiol, estrone, and androgen,(53-55) and increased concentrations of sex 

hormone binding globulin.(56) One published randomized clinical trial has shown 

that a moderate exercise program reduces endogenous sex hormones in overweight/ 

obese sedentary postmenopausal women.(57, 58) Cross-sectional data from the 

Women’s Health Initiative show that both a sedentary lifestyle and increased 

body weight are significantly related to increased blood levels of estrogens in 

postmenopausal women.(59) 

Weight and Body Composition 

Postmenopausal Breast Cancer 

Body mass index (BMI) is the most common measure of adiposity used in studies 

of weight, adiposity, and breast cancer. Obesity experts have developed the 

following categories of adiposity based on BMI: underweight (30.0 kg/m2). (60) 

More than 100 studies have reported on the association of weight or BMI at 

different ages, central fat distribution, or adult weight gain and risk of breast 

cancer incidence.(61) Taken together, these studies found that women who are 

overweight or obese have a 30 – 50% increased risk for postmenopausal breast 

cancer development compared with normal-weight women. In contrast, overweight 

and obesity decrease risk of breast cancer occurring during the premenopausal 

years. The Women’s Health Initiative Observational Study is a multi-ethnic, multisite 

cohort study of women aged 50 – 79 at study entry.(62) Women underwent 

several clinic measures of weight and body mass when entering the cohort, 

including height, weight, waist, and hip circumferences, and self-reported lifetime 

weight history. Among who had never used menopausal hormone therapy, women 

with a BMI >= 31.1 kg/m2 had a statistically significant 2.5 times greater risk of 



developing breast cancer compared with women whose BMI was 22.6 kg/m2 or 

less (63). The Nurses’ Health Study also observed a 60 percent increased risk for 

postmenopausal breast cancer associated with overweight and obesity in women 

who had never use menopausal hormone therapy.(64) Results of case-control 

studies are similar to those of cohort studies.(61) 

Premenopausal Breast Cancer 

The association of weight and adiposity with risk for premenopausal breast cancer 

differs from that in postmenopausal breast cancer. In particular, weight or BMI 

are slightly inversely related to premenopausal breast cancer risk. In a recent 

meta-analysis of BMI and cancer incidence (65) that included 20 epidemiologic 

studies of BMI and premenopausal breast cancer, the overall summary relative risk 

of premenopausal breast cancer for each 5 kg/m2 increase in BMI was 0.92 (95% 

CI 0.88-0.97, p < 0.001). A recent study of 113 130 premenopausal participants 

(with 1398 cases of incident breast cancer) in the Nurses’ Health Study II cohort 

reported a significant linear inverse trend between current BMI and breast cancer 

incidence (P < 0.001) that was not explained by menstrual cycle characteristics or 

infertility due to an ovulatory disorder (covariate- adjusted hazard ratio for breast 

cancer in women with a BMI > 30 kg/m2 vs 20.0-22.4 kg/m2, 0.81; 95% CI, 0.68- 

0.96). (66) BMI at age 18 years was the strongest predictor of breast cancer risk 

(covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 

18 years > 27.5 kg/m2 vs 20.0-22.4 kg/m2 was 0.57; 95% CI, 0.41-0.81). The 

inverse association of BMI with premenopausal breast cancer risk was limited to 

hormone receptor positive breast cancers. 

These data on BMI and premenopausal breast cancer is particularly relevant to Arab 

women in the Kingdom of Saudi Arabia, where the median age at breast cancer 

diagnosis is 50 years, likely representing a high proportion of cases developing 

in the premenopausal years (67). It is not clear why premenopausal breast cancer 

differs from postmenopausal breast cancer with respect to adiposity, but one 

hypothesis is that obese girls, teenagers, and premenopausal women have fewer 

ovulatory cycles and therefore are exposed to lower levels of ovarian hormones 

including estrogens, progesterone, and testosterone compared with normal-weight 

girls and young women (68). 

Adult Weight Gain 

Weight gain during adulthood has been consistently associated with increased 

risk for postmenopausal breast cancer.(63, 64, 69-76) Findings from two large 

cohort studies suggest that the doubling of risk associated with a gain in BMI 

from age 18 greater than 9.7 kg/m2 (Women’s Health Initiative) or a weight gain 

great than 20 kg (Nurses’ Health Study) is limited to women who had never used 

postmenopausal menopausal hormone therapy.(63, 64) In these studies, a 20% 

increase in risk was observed for BMI gains between 3.5 – 6.2 kg/m2 (Women’s 

Health Initiative) or weight gains between 2 to 20 kg (Nurses Health Study). 

Increased adult weight gain has also been found to be a consistent predictor of 

increased risk for breast cancer in case-control studies.(61) 

Abdominal Fat 

High levels of abdominal fat have been associated with up to a doubling of breast 

cancer risk among postmenopausal women in a small number of cohort studies 

compared low levels of abdominal fat,(63, 69, 72, 77, 78) independent of BMI. In 

the Women’s Health Initiative, statistically significant trends of increasing breast 

cancer risk with increasing waist and hip circumferences were observed among 

women who had never used menopausal hormone therapy.(63) Women in the 

highest quintile of either waist or hip circumference had approximately twice the 

risk for breast cancer development compared with women in the lowest quintile. In 

the Nurses’ Health Study, the relative risk among women in the highest vs. lowest 

quintile of waist circumference was 1.2 among women overall and 1.9 among women 

who had never used menopausal hormone therapy.(64) However, not all studies 

have found an association of abdominal circumference with breast cancer risk. 

Effect of Intentional Weight Loss 

There are few data on the association of weight loss and breast cancer risk. In 

three studies, weight loss occurring over a prolonged interval was associated with 

a non-statistically significant reduced risk.(69, 70, 79) In another study, weight 

loss in the decade before diagnosis was also associated with a non-statistically 

significant decreased risk.(76) One study in premenopausal women aged 44 

years or less found a statistically significant 36 percent decreased risk with 

weight loss from age 20 to interview that was limited to cases with low-grade 

tumors.(80) One study in postmenopausal women aged 50 – 74 years found a 

statistically significant 24 percent decreased risk of breast cancer with weight loss 

from age 18 to interview.(74) In an analysis in the Nurses' Health Study, 87,143 

postmenopausal women, aged 30 to 55 years and free of cancer were followed 

for up to 26 years (1976 – 2002) to assess effects of lifetime weight change on 

breast cancer risk. (81) A total of 4393 cases of invasive breast cancer were 

documented during this follow-up. Compared with those who maintained weight, 

women who gained 25.0 kg or more from age 18 years had a 45 percent increased 

risk of breast cancer that was statistically significant. Among women who had 

never taken menopausal hormone therapy, those who gained 25 kg. or more had 

almost a doubling of risk of breast cancer compared with those who remained 

weight stable. Compared with weight maintenance, women who gained 10.0 kg 

or more after menopause had a statistically significant 18 percent increased risk 

of breast cancer occurrence. Women who had never used menopausal hormone 

therapy, lost 10.0 kg or more since menopause, and kept the weight off had less 

than half the risk of breast cancer compared with those who maintained weight, 

and the result was statistically significant. The researchers estimated that 15.0% 

of breast cancer cases in the Nurses’ Health Study cohort could be attributable to 

weight gain of 2.0 kg or more since age 18 years and 4.4% could be attributable 

to weight gain of 2.0 kg or more since menopause. Among those who did not use 

menopausal hormone therapy, these attributable risks were 24.2% for a weight 

gain since age 18 years and 7.6% for weight gain since menopause. 

The majority of the studies on weight and breast cancer risk have been conducted 

in European and North American populations. Nevertheless, the available data 

suggest that increased adiposity increases risk for breast cancer across geographic, 

cultural, race, and ethnic groups.(2) 

Mechanisms 

There are several likely mechanisms linking increased adiposity to risk for 

postmenopausal breast cancer. After menopause, adipose tissue is the main site 

of estrogen production through aromatization of androgens to estrogens.(52) 

Overweight and obese postmenopausal women have high concentrations of estrone, 

estradiol, testosterone and low concentrations of sex hormone binding globulin, 

compared with leaner women.(55) Testosterone concentrations are increased in 

both premenopausal and postmenopausal overweight/obese women compared 

with leaner women, perhaps due to increased conversion of androstenedione to 

testosterone in adipose tissue.(82) In a recent study using a random sub sample of 

women in the Women’s Health Initiative Dietary Modification Trial, women with 

a high BMI and low self-reported physical activity, had higher levels of estrone, 

estradiol and free estradiol, and lower levels of sex-hormone binding globulin 

(SHBG) than women a similar BMI who were active as well as those with low 

BMI in either activity category.(59) 


Insulin promotes cancer cell growth, and therefore could explain part of the link 

between increased adiposity and breast cancer risk, because overweight and 

obese women have increased blood insulin levels compared with normal-weight 

women.(83) Insulin-like growth factors (IGFs) stimulate cell turnover in most 

body tissues, and have been associated with increased risk of breast cancer.(84) 

IGF is down-regulated by increased production of its binding protein (IGFBP-1), 

which can result from increased exercise, decreased caloric intake, and decreased 

body weight.(85, 86) Decreased IGF activity may increase the hepatic synthesis 

of sex hormone binding globulin, resulting in diminished availability of free sex 

hormone. Thus, increased exercise could result in lowered biologically available 

endogenous sex hormones via a cascade of metabolic and hormonal events, and 

thus a lowered risk of breast cancer. 

Diet 

The large international and temporal variations in risk for breast cancer prompted 

interest in possible dietary causes of breast cancer.(3) Several studies examined 

particular international and inter-cultural dietary differences, and proposed that diets 

that are low in fat and high in fruits, vegetables, fiber, and complex carbohydrates 

might lower risk for breast cancer.(87, 88) Although prospective observational 

studies in humans have generally not supported this hypothesis, several animal 

experimental studies have provided support for an association between certain 

dietary patterns and reduced risk for breast cancer.(89) Animal experimental studies 

have shown increased development (via promotion of tumorigenesis) of mammary 

tumors with increased polyunsaturated or saturated fats intake.(3) However, it is 

not clear if the dietary fat per se, or the increased energy intake, was responsible 

for the increased development of mammary tumors in these studies. Indeed, recent 

animal model evidence shows that both caloric restriction and increased exercise 

reduce mammary tumor development (90, 91) 

Human experiments have tested the effects of low fat and high fiber diets on some 

breast cancer biomarkers such as mammographic density and blood estrogens. 

The effect of a low-fat, high vegetable and fruit diet on mammographic density 

was tested in a randomized clinical trial in 817 women.(92) Women randomized 

to the diet arm experienced a 6.1% decrease in mammographic density over two 

years compared with a 2.1% decrease in controls (p = 0.01). Several clinical trials 

have shown a reduction in circulating estrogen levels with institution of a low-fat 

dietary pattern,(93) although there is still a question regarding whether it was the 

diet per se, or the weight loss resulting from the dietary changes, that caused the 

reduction in hormones.(94) 

The Women’s Health Initiative Dietary Modification clinical trial, begun in 

1993, included over 48,000 postmenopausal women aged 50 – 79 from diverse 

geographic, cultural, race and ethnic groups around the United States.(95) Women 

were randomly assigned to diet modification (40%) or comparison group (60%). 

The dietary modification goal was 20% calories from fat, 5 servings of fruits/ 

vegetables per day, and 6 servings of grains per day. During follow-up, dietary fat 

intake was significantly lowered in the dietary modification group compared with 

the comparison group. The difference between groups in change from baseline 

for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. 

Vegetable and fruit consumption was higher in the intervention group by at least 

1 serving per day. Over the 8.1-year average follow-up period, a total of 655 

women developed invasive breast cancer in the intervention group and 1072 in 

the comparison group, which resulted in a nine percent reduction in risk in women 

in the diet group versus control that was not statistically significant. Additional 

analyses suggested a lower risk among women who reduced dietary fat intake to 

the greatest degree, provided evidence of risk reduction among women having 

a high-fat diet at baseline, and suggested a dietary effect that varies by hormone 

receptor characteristics of the tumor. 

While increased intake of dietary fat per se has not been established as a risk 

factor for breast cancer, increased dietary fat typically increases caloric intake. 

This results in overweight and obesity, which are consistent risk factors for 

postmenopausal breast cancer. Therefore, prudent advice for women wanting to 

avoid lifetime weight gain, overweight, and obesity, would be to follow a diet 

that is low in dietary fat. 

Vegetables and Fruits 

Early epidemiologic studies suggested an association of increased intake of 

vegetables and fruits with decreased risk for breast cancer.(3) A combined analysis 

of eight cohort studies representing 351,825 women (7377 breast cancer cases), 

however, found no association between intake of vegetable and fruits and risk 

of breast cancer.(96) 

Soy, Isoflavones, and Lignans 

Epidemiologic studies indicate that increased consumption of soy products is 

associated with reduced risk for breast cancer.(66, 93) Many soy-based foods are 

available, including tofu, soy milk, soy cheeses, frozen “yogurt,” breakfast shakes, 

soy nuts, meat substitutes, and salad dressings.(97) Recent evidence suggests, 

however, that genistein, one component of soy, may promote the growth of some 

estrogen-sensitive tumors and reduce the efficacy of tamoxifen. This emphasizes 

the need for additional studies to determine whether soy is safe for women with 

breast cancer or who are at high risk for breast cancer.(98, 99) 

Phytoestrogens can act as weak estrogens and as estrogen antagonists, depending 

on the hormonal status of the woman. Thus, increased phytoestrogen intake such 

as soy can compete with endogenous estrogens in premenopausal women, and 

reduce overall estrogen exposure to the breast. Conversely, phytoestrogens can 

increase estrogen activities in women with low endogenous levels of estrogens, e.g. 

postmenopausal women, and thereby increase the breast’s exposure to estrogen. 

These findings have been observed in animal experiments and in a small number 

of human experimental studies.(3, 100-102) 

Meat and Dairy 

Some studies have suggested that increased intake of meats increases risk for 

breast cancer development, but other studies have not supported this.(3) Part of the 

discrepancy in findings may be the different levels of carcinogens and mutagens 

included in meat in different areas around the world. 

Intake of dairy foods has not been found to be associated with risk for breast 

cancer, and a recent report from a large cohort study found that increased intake 

of low-fat dairy products in premenopausal women was associated with decreased 

risk of breast cancer.(103) In that study, the multivariable relative risks comparing 

more than 1 serving per day vs. 3 or fewer servings per month intake categories 

were 0.68 (95% CI = 0.55 to 0.86) for low-fat dairy foods and 0.72 (95% CI = 

0.56 to 0.91) for skim/low-fat milk. The fat content of high-fat dairy products may 

promote increased risk for breast cancer through increasing energy intake in the 

diet. On the other hand, the high calcium and vitamin D content of supplemented 

dairy products may be protective against breast cancer.(103) 

Vitamins and Minerals 

Several epidemiologic studies have investigated the association between dietary 



and supplement intake of various vitamins and minerals, and risk of breast 

cancer. Specific micronutrients that have been associated with decreased risk 

include carotenoids, folate, calcium, vitamin D, lycopene, and vitamin C.(3, 

104-106) The studies have had mixed results, however, and because they have 

all been observational, are not conclusive. Recently, several studies have found 

an association between low blood levels of vitamin D and risk for breast cancer 

(107) Each of the studies categorized vitamin D levels differently, but overall it 

appears that women who had levels below the clinically “normal” levels had an 

increased relative risk for breast cancer compared with women with the highest 

blood levels. A protective effect of vitamin D, if substantiated, is relevant to Saudi 

Arabia, where many of the women have low blood levels of vitamin D due to 

low sun exposure. 

Relevance to Women of the Kingdom of Saudi Arabia 

Several of the dietary and lifestyle factors described above are relevant to women 

of the Kingdom of Saudi Arabia. The prevalences of overweight/obesity in Saudi 

women is estimated to be over 75 percent (108). Physical activity levels in 

Saudi women are extremely low (109). Vitamin D levels in Saudi women are 

reportedly low (110), likely due to decreased sun exposure, obesity, and lack of 

dietary supplementation. These lifestyle factors will likely result in an increased 

incidence of breast cancer in the future in Saudi Arabia. Therefore, there are several 

nutritional and lifestyle factors that could be promoted among Saudi women to 

reduce risk for breast cancer: 

1. Reduce overweight and obesity and maintain a normal weight over the 

lifetime by reducing calorie intake and increasing physical activity. The 

preferred dietary pattern for maintaining normal weight is low in fat, high 

in vegetables and fruits, and low in refined carbohydrates. 

2. Engage in at least 150 minutes per week of aerobic physical activity. This 

could be done with brisk walking, with home stationary bikes, with active 

housework or gardening, with the use of home instructional videos, or 

in classes specially designed for women. Participation in athletics is not 

necessary for women to become physically active. Encouragement of gym and 

active play activities for girls would be beneficial for reducing breast cancer 

risk and for reducing incidence of overweight and obesity in young women. 

3. Increase vitamin D intake through supplementation. In the U.S. the 

recommended minimal daily intake of vitamin D3 is 400 – 1000 IU/day. In 

Saudi Arabia, with low sun exposure in women, consideration for testing 

and supplementing vitamin D blood levels could have wide health benefits, 

as vitamin D is thought to reduce risk for several other chronic diseases. 

Lifestyle Factors and Prognosis in Women with Breast Cancer 

Once women develop breast cancer, they may be at increased risk of recurrence 

and poorer survival if they are overweight or obese. The effects of obesity on 

cancer outcome are substantial, where observed, and of potentially great clinical 

importance. The prevalence of overweight and obesity is higher in patients with 

some forms of cancer, compared with individuals from the general population 

(IARC). Compounding this is that weight gain after diagnosis is common in 

some breast cancer patients, especially among those receiving systemic adjuvant 

therapy. (111, 112) Weight gain during the post-breast cancer diagnosis period 

has also been associated with an adverse effect on recurrence risk and survival. 

(111) In addition to adversely affecting prognosis, overweight and obesity also 

increase the risk of several complications from cancer treatment, and increase 

risk of several co-morbidities. There are several potential mechanisms that might 

explain the link between increased adiposity and reduced prognosis, including 

hormonal, inflammatory, and immune system effects. Although definitive clinical 

trials testing weight loss effects on prognosis in breast cancer patients have not 

been conducted, strategies for weight control may be helpful for some breast 

cancer patients and survivors. 

Obesity and Breast Cancer Mortality – Non-Patient Populations 

In the American Cancer Society Prevention Study II, a prospective cohort study 

in 900,000 American adults, 57,145 cancer deaths were identified during 16 years 

of follow-up.(5) Cancer mortality was determined through personal inquiries and 

linkage with the National Death Index. The relative risks (RR) for breast cancer 

for increasing category of BMI, compared with women with BMI 40.0). The test for trend was highly significant (p Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info

were measured in a fasting state prior to initiation of adjuvant treatment in 535 

women with T1-3, N0-1, M0 breast cancer. After a median 50 months follow-up, 

obesity predicted distant disease-free and overall survival (p


A recent study investigated whether activity undertaken prior to diagnosis 

influenced breast cancer survival in a population-based cohort of 1264 women 

ages 20 to 54 years who were diagnosed with invasive breast cancer between 

1990 and 1992 and followed for 8 to 10 years with 290 deaths. For women in the 

highest quartile of activity in the year before diagnosis compared with the lowest 

quartile, risk of dying from breast cancer was reduced by 22 percent. High activity 

was associated with a 30 percent reduced risk of death among women who were 

overweight or obese at the time of diagnosis that was statistically significant, but 

not among normal-weight or underweight women.(132) 

Dietary Composition and Breast Cancer Prognosis 

In the Women’s Intervention Nutrition Study (WINS), 2437 women with breast 

cancer were randomly assigned between 1994 – 2001 in a ratio of 40:60 to dietary 

intervention (n = 975) or control (n = 1462) groups and followed for a median 

60 months. Dietary fat intake was lower in the intervention than in the control 

group (33.3 versus 51.3 fat grams/day at 12 months, respectively), corresponding 

to a statistically significant (P = .005), 6-pound lower mean body weight in the 

intervention group. A total of 277 relapse events (local, regional, distant, or 

ipsilateral breast cancer recurrence or new contralateral breast cancer) were reported 

in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women 

in the control group. The hazard ratio of relapse events in the intervention group 

compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for 

stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory 

analyses suggested a greater effect of the dietary intervention among women with 

hormone receptor negative tumors.(133) 

Potential Mechanisms for an Adverse Prognostic Effect of Obesity 

Several mechanisms have been proposed for an adverse prognostic effect of 

obesity in cancer.(111) These mechanisms include increased levels of circulating 

hormones such as estrogen and androgens; reduced levels of sex hormone binding 

globulin (SHBG) which thereby increases the levels of free estradiol and free 

testosterone; increased levels of insulin and insulin-like growth factors; reduced 

levels of insulin-like growth factor binding globulin; increased levels of leptin; 

increased levels of cytokines; effects of diet; reduced immune functioning; and 

chemotherapy underdosing in obese patients. Although some biological evidence 

exists to support many of these potential mechanisms, there is little direct evidence 

of their role. 

Estrogens, Androgens, and Adiposity in Women 

Estrogens can promote growth of several hormone-dependent tumors, particularly 

breast and endometrium, and conversely, anti-estrogens or withdrawal of 

endogenous estrogens are effective adjuvant treatments for breast cancer. 

(134, 135) Postmenopausal women produce estrogens in fat and other tissue 

through the aromatization of androgens to estrogens. The enzyme aromatase is 

abundantly present in adipose tissue, especially subcutaneous fat. Estrogens are 

tumor promoters in vitro and in vivo, and women with high circulating levels of 

estrogens are at increased risk of developing breast cancer.(46) 

Postmenopausal women who are overweight or obese have elevated levels of 

estrogens compared with lighter-weight women. In a population-based cohort of 

505 postmenopausal women with Stage 0-3a breast cancer (the Health, Eating, 

Activity, Lifestyle – HEAL – Study), adiposity was positively and statistically 

significantly associated with circulating levels of estrone, estradiol, and free 

estradiol.(136) Women were recruited to this study through the Surveillance, 

Epidemiology, and End Results (SEER) cancer registries of Western Washington 

and New Mexico, and were primarily non-Hispanic and Hispanic Whites. Between 

4 – 12 months after diagnosis, anthropometric measures and blood draws were 

obtained on all women and DEXA scans were obtained on 415 women. Obese 

women (BMI >30) had 35% higher concentrations of estrone and 130% higher 

concentrations of estradiol, compared with lighter women (BMI Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info

Abdominal Fat 

The body fat that is stored in the intra-abdominal area is thought to have special 

physiological properties, and is more associated than other body fat with risk 

factors for diabetes and cardiovascular disease. Increased intra-abdominal fat is 

associated with increased levels of insulin and total and LDL cholesterol. 

The role of visceral fat on cancer prognosis has not been established. Increased 

intra-abdominal fat, however, is associated with increased circulating levels of 

serum insulin and glucose,(138) and as described above, insulin may be a tumor 

growth promoter. Therefore, interventions that decrease intra-abdominal fat levels 

may be hypothesized to improve cancer prognosis. In a small study, a 2-month 

low-fat diet and structured exercise intervention in women with a history of breast 

cancer resulted in a significant decrease in waist circumference.(139) In a clinical 

trial in 173 postmenopausal overweight-obese sedentary women without breast 

cancer, exercise significantly decreased intra-abdominal fat.(138) 

Obesity is also associated with inflammatory markers including C-reactive protein, 

serum amyloid A (SAA), interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor 

necrosis factor-α (TNF-α), some of which been shown to be higher in patients 

with metastatic cancer compared with normals and with persons with early cancer. 

(111) Despite a paucity of data, it seems plausible that patients with depressed 

immune function might be at increased risk of tumor progression. Studies suggest 

decreased immune function in obese individuals, and increased immune function 

with exercise in breast cancer survivors.(140) 

Methods for Weight Loss and Maintenance for Breast Cancer Patients 

There are several methods for weight loss or control that have been tested in the 

general population(141) or in persons with other obesity-related conditions such as 

diabetes and cardiovascular disease.(142) Detailed guidelines for the identification, 

diagnosis, and treatment of overweight and obesity have been published by several 

institutes of the National Institutes of Health,(141) and recently from the U.S. 

Preventive Task Force.(143) There are no specific guidelines for weight loss or 

maintenance methods in breast cancer patients or survivors, however. 

The first step for clinicians should be the assessment of body composition including 

BMI.(143) For overweight (BMI 25.0 – 29.9 kg/m2) or obese (BMI >30 kg/m2) 

patients, physicians can then apply a weight loss strategy as outlined by the NHLBI 

Obesity Education Initiative Expert Panel.(141) (The clinician should be aware 

that BMI does not always accurately reflect adiposity. Thus, for example, very 

muscular or athletic women may have a BMI above 25.0, without excess adipose 

tissue.) The NHLBI Obesity Education Initiative Expert Panel recommends a 

weight loss treatment algorithm that combines dietary therapy, physical activity, 

and behavioral treatment, provided on an ongoing basis to promote weight loss 

and maintenance. For select patients, additional therapies such as medications 

and surgery could be considered. 

Behavioral Weight Loss Therapy 

Reviews of randomized trials in healthy obese individuals and in those at high risk 

for other diseases (e.g. pre-diabetics, hypertensives) show that the combination of 

diet and behavioral treatment typically delivered in 15 to 24 weekly groups sessions, 

produces an average weight loss of approximately 8.5 kg (mean body weight 

reduction = 9%).(141) This degree of weight loss is associated with significant 

improvements in blood pressure, blood glucose and psychological well being. In 

the year following behavioral treatment participants regain typically 30% – 40% 

of their lost weight. However, relatively few studies have provided behavioral 

treatment lasting more than six months, and follow-up studies conducted 2 to 5 

years after behavioral treatment have documented a gradual return to baseline 

weights in most individuals. Long-term success is more likely when participants are 

provided with extended treatment programs. Support for the efficacy of extended 

lifestyle treatment has been well documented.(141) 

Weight Loss Diets 

The success of most dietary weight loss therapies has rested on reducing caloric 

intake below that required for current weight maintenance, e.g. creating a negative 

energy balance. A low-fat, reduced calorie diet has been shown to produce significant 

weight loss when combined with behavioral change counseling.(141) The first 

step in most weight loss diets is self-monitoring, where the individual records all 

food eaten each day. Then, the daily intake of calories, fat, fiber, carbohydrates, 

or all of these, can be tallied by the individual or weight loss counselor. Another 

key step is frequent and regular weighings by a health professional or weight loss 

counselor. A major key to sustained weight loss is to achieve life-long dietary 

pattern changes, rather than short term “crash” diets. 

There is preliminary evidence that very-low-carbohydrate diets may work through 

additional mechanisms beyond simple calorie restriction, and produce greater 

weight loss compared with low calorie diets,(144, 145) although over a year, low 

carbohydrate diets may not be more efficacious than reduced calorie diets.(145) 

All diets have similar issues, in that most patients regain weight within a year 

after initial weight loss.(143) 

Weight Loss Pharmacotherapy 

For obese patients, or for those with BMI >27 with serious co-morbidities, weight 

loss medications may be a useful adjunct to diet and exercise therapy.(143, 146) Two 

medications are currently available in the United States for weight loss, and both 

are efficacious in the short term, although long-term efficacy data are not available. 

Sibutramine, a dopamine, norepinephrine, and serotonin reuptake inhibitor inhibits 

appetite through a central mechanism. In a review of 7 randomized clinical trials, 

sibutramine combined with lifestyle change promoted weight loss of 2.8 to 4.2 

kg over 8 to 52 weeks in healthy adults and those with controlled hypertension. 

(146) However, patients regained weight after cessation of treatment. Orlistat, a 

gastrointestinal lipase inhibitor, prevents fat absorption. In 10 randomized trials, it 

has produced an average 3.5 kg weight loss over 1 – 2 years, in excess of control 

(lifestyle alone) weight loss. A more recent review with updated trial data(143) 

concluded that therapy with sibutramine or orlistat combined with lifestyle change 

produced weight loss of 3 to 5 kg over that of control (lifestyle alone), and that 

prolonged use continued this weight loss over up to 2 years. Two other medication, 

phentermine and mazindol produced similar weight loss in the short term, but are 

not approved for long-term use. This same review concluded that three additional 

medications showed mixed results: metformin, diethylproprion, and fluoxetine. 

None of these medications have been specifically tested in breast cancer patients 

or survivors, and therefore their effects on prognosis or other aspects of the cancer 

experience are unknown. 

Bariatric Surgery 

For severely obese persons (BMI >40.0) or for patients with serious co-morbidities 

for whom obesity poses an extreme risk, more invasive methods of weight loss 

can be considered such as bariatric surgery.(147) The effect of weight loss surgery, 

however, has not been tested in persons who have had breast cancer, and is likely 

to only be appropriate for women with very early stage disease. 



Exercise and Weight Loss and Maintenance 

Physical activity may provide a low-risk method of preventing weight gain and 

promoting maintenance of weight loss in overweight and obese men and women. 

(148) Studies have shown losses in total body weight from exercise training 

without dieting.(123) In a review of several hundred studies of exercise training 

and weight loss, Wilmore concluded that the average weight loss over 12 months 

of exercise training would amount to only 3.2 kg.(149) Unlike weight-loss dietary 

interventions, physical activity also increases or maintains muscle mass and 

increases cardiorespiratory fitness levels. 

Weight Loss Studies in Breast Cancer Patients and Survivors 

Studies of weight loss reduction in breast cancer patients have been few and with 

mixed results. The Mayo Clinic randomized 107 breast cancer patients to monthly 

non-intensive dietician counseling. Median weight increase at six months was 2 

kg in the counseling group versus 3.5 kg in the control group, a nonsignificant 

difference.(150) Goodwin evaluated a multidisciplinary approach combining group 

dietary sessions, psychological support groups, and exercise programs in 61 breast 

cancer patients. For women with BMI >25 kg/m2, weight loss was 1.63 ± 4.22 kg, 

and aerobic exercise increase was a strong predictor of successful weight loss.(116) 

In a study of 34 obese breast cancer survivors, a combination of individualized 

counseling and Weight Watchers program produced greater weight loss than 

either alone or control.(151) Weight change after 12 months of intervention was: 

+0.85 kg in the control group, -2.6 kg in the Weight Watchers group, -8.0 kg in 

the individualized counseling group, and -9.4 kg in the comprehensive group that 

used both individualized counseling and Weight Watchers. Weight loss relative to 

control was statistically significant in the comprehensive group 3, 6, and 12 months 

after randomization, whereas weight loss in the individualized group was significant 

only at 12 months. The study resulted in weight loss of 10% or more of initial body 

weight in 6 of 10 women in the comprehensive group after 12 months. These same 

researchers found that the comprehensive group experienced significant declines 

in leptin and improvements in lipids.(152) de Waard and colleagues randomized 

102 postmenopausal women (median BMI 27 kg/m2) with a recent breast cancer 

diagnosis to a weight loss program involving step-wise reduction in caloric intake 

versus a control group. After one year, median weight loss was 6.0 kg with the 

intervention (p Pan Arab Journal of Oncology | vol 3; issue 1 | March 10 www.amaac.info

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CHALLENGES OF CANCER SCREENING PROGRAM 

Abulkhair O. 1 , Al Amro A. 2 , Jazieh AR. 1 

(1) King Abdulaziz Medical City, Riyadh 

(2) King Fahad Medical City, Riyadh 

Corresponding Author: Dr. Omalkhair Abulkhair 


Department of Oncology, King Abdulaziz Medical City 

P.O. Box 22490, Riyadh 11426, Kingdom of Saudi Arabia 


Background 

Cancer is a global public health problem. It is the second leading cause of death 

worldwide. It is often regarded as a disease cause of the developed world, but 

with improved living standards, incidence in low and middle income countries 

is on the rise. By the year 2030, seven out of every ten new cases will occur in 

the developing world.1 

Survival outcomes vary dramatically throughout the world and variation in access 

to quality cancer care is a major cause of these discrepancies.2 Over 40% of more 

than 7 million cancer deaths can be prevented. Furthermore, cancer is curable if 

detected early and treated adequately. This applies in particular to breast cancer, 

colon, prostate, and cervical cancer as the technology for screening, diagnosis 

and treating is mature. 

A recent publication about the future burden of breast cancer in Saudi Arabia which 

anticipated the incidence and mortality of cases will increase by about 350% and 

160% respectively over a ten-year period.3 

Saudi Society for Cancer recognized the importance of prevention and early 

detection. In an effort to combat cancer through early detection, Abdulatif 

Charitable Screening Center was established as the first dedicated Cancer Screening 

Center in the Kingdom. 

The objective of this manuscript is to address the challenges/barriers which 

were encountered. Data related, center related, personal related challenges were 

identified, different interventions were implemented for each barrier. Furthermore, 

we will review the planning strategies for such project. This information may be of 

benefit to health care providers, health care organizations and health care systems 

personnel when considering establishing public cancer screening programs. 

Readers are advised to review the World Health Organization (WHO) guide for 

effective programs which includes six modules that provide practical advice for 

program manager and policy makers on how to advocate, plan and implement 

effective cancer control programs, prevention and early detection. 

Methods 

The Abdulatiff Charitable Screening Center is the first center in Saudi Arabia to 

conduct early diagnosis of breast cancer initially but then to cover screening for 

cervical, colon and prostate cancers. The Center inauguration has started screening 

in October 2007. 

The center is governed by Board of Directors which comprised of experts and 

leaders in the field of cancer diagnosis and treatment. The Center is empowered 

with a stand alone management and policy and procedure to ensure accurate 

screening and referral to tertiary care centers. 

Identifying Barriers 

The initial contact helped to identify centers barriers and concerns which can be 

summarized as follows: 

1. Concept Approval 

The involvement of charity organization in screening is of great concern since 

screening is a project which needs careful planning, budgeting, and control. The 

delay in establishing national screening program and cloudy strategy forced the 

Saudi Cancer Society to establish the first screening center. We realized that no 

public awareness program will be successful unless there are centers ready to 

screen candidates. 

2. Financial barriers 

Establishing screening center requires substantial financial support not only for 

the initial start up cost but for the running expenses of the center on ongoing 

basis especially if the center does not charge the patients. A decision was made 

to make screening free of charge in order to remove “out of pocket” expenses as 

barrier for participation. 

This center was a donation from a businessman who donated million Saudi Riyals 

which include the building and operation of first year. The plans took place to 

establish 8 million USD (30 million SR) endowment for society in Riyadh to 

secure permanent revenue to finance its activities. 

3. Personnel 

Assuring adequate staffing to run the center was major challenge which delayed 

the opening of the center for considerable time. There was a need for a family 

physician, a health educator, receptionist, mammography technician, and radiologist 

to read mammogram. 

4. Data Collection/Confidentiality: 

In order to identify possible risk factor and perform quality control and to develop 

a recall system, predetermined data should be collected and entered into unified 

database. This was an important barrier identified few months after operation 

and when number of cases increase and in order to overcome this problem, new 

software will be applied. 

5. Recall System 

To overcome such problem, a form designed which has all personal information 

including ID and phone problem. Patient with abnormal mammogram findings 

where called back for further testing and work-up. 

6. Referral Process 

The center is designed to perform screening only. Therefore, collaboration with 

tertiary care centers was mandatory to ensure confirmation of diagnosis and 

further therapy. So, a proposal was submitted to all tertiary hospitals. However, 

for the initial 8 months, only two centers cooperate to have the suspicious cases 

for further investigation. So, lack of health facilities was an issue and we tried to 

overcome with cooperation with three tertiary care centers though, not all these 

hospitals have all needed resources in terms of performing investigation and 

access to cancer specialists. 



7. Barriers to Participation 

The center stared in August 2007, the flow of cases was very slow and that was 

attributed to cultural/social barriers that by diagnosis of breast cancer, women will 

lose her role in live.4 Lack of knowledge among female which has been reported 

by many studies done in different regions of Saudi Arabia and concluded lack of 

knowledge towards risk factors, breast cancer screening modality5, also diversity 

in health beliefs and behaviors which exist in religious subgroups.6 So, health 

communication should be modified to suit women in different groups to increase 

participation in screening. 

Other screening barriers include cultural knowledge and the use of traditional 

treatment,7 related fear, low self efficacy, fatalism, misinformation, and ineffective 

health communication.8 Through this center, more than 2500 ladies were screened; 

thus, far many participants barriers were identified. As listed above, the majority 

are related to attitude and lack of knowledge. To overcome this barrier, a wellorganized 

public health program was conducted throughout the year for ladies 

at work, schools, colleges/universities and public places such as Prince Salman 

Social Center, shopping mall, in addition to the use of media through a common 

popular TV program. This step had a good impact on increasing level of awareness 

and increase participation of women. This was noticed when the medial covered 

the opening of the center by USA former First Lady Laura Bush. The numbers 

of screened ladies increased 10 times over that before the opening ceremony, 

which reflects the importance and the vital role that media play in increasing 

public awareness. There was another important barrier that was reported through 

several studies which is the primary health care physician role in cancer prevention 

demonstrated by low adherence to prevention and screening recommendations as 

highlighted in several studies includes:9 

• Physician’s beliefs that prevention and not early detection of cancer is not 

part of their jobs. 

• Physicians / patients bond (lack of trust). 

• Lack of services and access to health care for prevention and screening. 

• Lack of time. 

• Lack of organized system. 

To overcome such issue, the Ministry of Health formed a committee for Breast 

Cancer Prevention and Early Detection to implement a program. In addition a 

National Society for Cancer Prevention was formed and it included many of this 

center board members. Furthermore, Cancer Prevention and Early Detection 

Symposia were held targeting primary health care physicians. 

Important barriers include screening-accompanied anxiety in waiting for further 

studies or confirmation of findings. To eliminate and shorten the period of time 

from screening until physician visit, we opened a special clinic for those referred 

from the center, and a coordinator assigned to open a file and facilitate the referral 

procedure in order to follow their referral to the hospital within a week from their 

referral to the tertiary center. 

In order to make sure that patients with suspicious lesions are properly managed, 

a flow system was established as illustrated in figures. 

Annual 

Follow-up 

Mammography 

Figure 1: Figure Patient 1: Patient flow diagram for for participants in the breast in the cancer breast screening cancer program. screening 

program. 

Table 1: Targeted Barriers for the Screening Program and Interventions 

Targeted Barriers Intervention 

Financial - Initial donation 

- Endowment 

Confidentiality - All women staff, closed space 

- ID for identification 

- Secure Database Site 

Staff shortage - 2 radiologists to read 

mammography for back-up 

Difficulty in retrieving data and data - Establishing database with new 

management 

software 

Lack of interest/misinformation from - Public awareness program 

patient and physician 

implemented throughout the year 

- Physician education symposia and 

5 

activities 

- High-profile media events 

Patient Care - Recall system 

- Work-up and management/referral 

process 

- Follow-up 

Conclusions 

In spite of having many barriers to public cancer screening, though we were able 

to screen more than 2500 women within 18 months period, many of these barriers 

were overcome by specific intervention. Good strategic planning with attention to 

the above challenges and following WHO cancer control program for implementing 

such center prior to establishing another center is advisable. 

References 

1. The World Health Organization Fight Against Cancer: Strategies that prevent, 

cure and care. 2007. www.who.int/cancer/en 

2. Agarwal G. et al. Breast Care 2008;3:21-27 DOI 10.1159/000115288 

3. E. Ibrahim. JCO Vol. 36, No. 155: May 2008;2009 

4. Baron-Epel. Mammography screening in a multi-ethnic population in Israel. 

Health Services Research. 42(3):1008-1019.2007 

5. Khadiga F. Dandash, Abdulrahman Al-Mohaineed. Knowledge, attributes and 

practicesurrounding breast cancer and screening in female teachers of Buraidah, 


Screening 

Center 

• Suspicious 

lesion 

R4/R5 

• R0 

• R3 

No Yes 

Annual 

Follow-up 

Mammography 

Referral 

Center for 

W/U 

Management 

by the Tertiary 

Center 

Negative 

for 

Malignancy 

Positive for 

Malignancy

Saudi Arabia. International Journal of Health Science. Vol. 1, Jan 2007 

6. Faisal Azaiza, Mini Cohen. Devloping and testing an instrument for identifying 

culture-specific barriers to breast cancer screening in Israel. Acta Oncologica. 

Volume 47, Issue 8 2008 

7. Little D. et al. Breast cancer in Asian women. Ethnomed. June 2, 2001. pp 

1570-1577 

8. M. Lamyian, A. Hydrania, et al. Barriers to and factors facilitating breast 

cancer screening among Iranian Women: A qualitative study. Health Journal 

Vol. 13 No 5:Sept. – Oct. 2007 

9. Layla A. Al-Alaboud, et al. The barriers of breast cancer screening program 

among PHHC female physicians. Middle East Journal of Family Medicine. Sept. 

2006; Vol. 6 Issue 5) 

ENDOMETRIAL CARCINOMA 

Faisal Al Safi, FRCSC 1 , Hany Salem 2 , Nashmia Al Mutairi 1 

(1) King Abdulaziz Medical City – National Guard Health Affairs, Riyadh, KSA 

(2) King Faisal Specialist Hospital and Research Center, Riyadh, KSA 

Corresponding Author: Dr. Faisal Al Safi , FRCSC, Department of Oncology 

(Mail Code 1777), P.O. Box 22490, Riyadh 11426, Kingdom of Saudi Arabia 

E-mail: safif@ngha.med.sa 

Endometrial carcinoma is the most common gynecologic malignancy in the United 

States; it accounts for 6 percent of all cancers in women. Fortunately, most cases 

are diagnosed at an early stage when surgery alone may be adequate for cure. 

Five-year survival rates for localized, regional, and metastatic disease are 96, 67, 

and 26 respectively [1]. 

Risk Factors 

Estrogen 

Treatment with estrogen alone increases the risk for endometrial hyperplasia and 

carcinoma. Endometrial hyperplasia can be demonstrated within one year in 20 to 

50 percent of women receiving unopposed estrogen [2]. Furthermore, any factor 

that increase exposure to estrogen[e.g., hormone replacement therapy, obesity, 

anovulatory cycles. estrogen–secreting tumor]increases the risk of endometrial 

cancer, whereas factor that decrease exposure to estrogens or increase progesterone 

level[e.g. oral contraceptives or smoking ] tend to be protective [3]. 

Tamoxifen 

Tamoxifen is a competitive inhibitor of estrogen binding to estrogen receptors 

that also has partial agonist activity (i.e., tamoxifen is a weak estrogen). It is used 

for adjuvant therapy in women with early stage breast cancer, as treatment for 

recurrent disease, and for reduction of breast cancer incidence in high-risk women. 

The site-specific activity of tamoxifen in different tissues is well recognized, 

suppressing the growth of breast tissue, but stimulating the endometrial lining. 

Tamoxifen use has been linked to development of endometrial pathology, both 

benign and malignant [4]. 

Diabetes and Hypertension 

Women with diabetes mellitus and hypertension are at increased risk for endometrial 

cancer, at least in part because of co-morbid factors associated with obesity. 

However, some studies have found independent effects as well [5]. 

Diet 

A diet containing high amounts of fat (especially animal fat) appears to be a risk 

factor for endometrial cancer, even after adjusting for caloric intake and body 

weight [6]. By comparison, two case-control studies showed that plant-based diets 

high in fiber, legumes (especially soybeans [7]), whole grain foods, vegetables, 

and fruits appear to reduce the risk of the disease [8]. 

Other risk factors include: 

Familial predisposition and lack of physical activity. 

Pathology 

The most common type of endometrial cancer is endometriod adenocarcinoma (75 

to 80 percent). Clear cell and papillary serous carcinomas account for 1 to 5, and 



5 to 10 percent of endometrial cancer cases respectively. Mucinous and squamous 

cell cancer comprises less than 2 percent of endometrial cancers. 

Clinical Features 

Ninety percent of patient with endometrial carcinoma have abnormal vaginal 

bleeding, most commonly postmenopausal bleeding. Occasionally, vaginal 

bleeding does not occur because of cervical stenosis, particularly in thin, elderly, 

estrogen-deficient patients. In some patients with cervical stenosis , a hematometria 

develops, and a small percentage have a purulent vaginal discharge resulting 

from pyometria. 

Diagnosis 

Endometrial biopsy 

Endometrial biopsy is the initial diagnostic test to rule out endometrial cancer 

in women with abnormal uterine bleeding or endometrial cells on Pap smear. 

Dilatation and Curettage with hysteroscopy and directed biopsy should be 

considered when the endometrial biopsy is nondiagnostic, but there remains a 

high suspicion of cancer (e.g., hyperplasia with atypia, presence of necrosis, 

pyometra, or persistent bleeding). 

Transvaginal ultrasonography 

Transvaginal ultrasound can be used to evaluate the endometrium by measuring the 

endometrial wall thickness. In postmenopausal women, an endometrial thickness 

of less than 4 to 5 mm is associated with a low risk of endometrial disease [9-10]; 

a thicker lining should be further evaluated by office biopsy, hysteroscopy with 

directed biopsy, or D&C. Cancer becomes increasingly more frequent relative to 

benign disease as the endometrial thickness approaches 20 mm, which was the 

mean endometrial thickness in 759 women with endometrial cancer [10] . 

Management 

The cornerstone of treatment for endometrial cancer is total abdominal hysterectomy 

and bilateral salpingo-oophorectomy, and this operation should be performed in 

all cases whenever feasible. In addition, many patients require some type of 

adjuvant radiation therapy to help prevent vaginal vault recurrence and to sterilize 

occult disease in lymph nodes. Chemotherapy in endometrial cancer is only of 

palliative value [11]. 

Screening 

General population 

Screening for endometrial cancer is generally not warranted in asymptomatic 

women. Many cases are diagnosed at an early stage since the malignancy 

commonly causes abnormal vaginal bleeding. Moreover, adequate inexpensive, 

noninvasive screening tests are not currently available. Although endometrial cancer 

occasionally is diagnosed after endometrial or glandular cells are discovered on 

Pap smear, the sensitivity of the Pap smear for detection of endometrial cancer is 

low and not sufficient to recommended it as a screening tool. Endometrial biopsy 

is more sensitive, but is relatively uncomfortable; equivocal tests may lead to 

additional unnecessary evaluation [12]. 

Women at risk of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) 

Women who are at risk of HNPCC are also at high risk (40 to 60 percent) of 

developing endometrial cancer. In fact, the risk of developing endometrial cancer 

may be slightly higher than the risk of developing colon cancer and endometrial 

cancer may be the first manifestation of malignancy [13]. These women also have 

a 12 percent lifetime risk of developing ovarian cancer [14]. 

Because of the high risk for development of endometrial cancer in women with or 

at risk of HNPCC, the American Cancer Society recommends that annual screening 

by endometrial biopsy be initiated by age 35 [15]. These recommendations cover 

the following: 

• Women who are known to carry HNPCC-associated mutations 

• Women who have a family member known to carry this mutation 

• Women from families with an autosomal dominant predisposition to colon 

cancer in the absence of genetic testing. 

At present, there are no data regarding the efficacy of this approach, nor is there 

a consensus on the optimal age (25 to 35) to begin screening. Annual or biennial 

pelvic ultrasonography has not been shown to be effective for early detection of 

endometrial cancer in these populations [16] 

These women should also be counseled about preventive measures, such as the 

option of prophylactic hysterectomy at complete childbirth. 

Patient on Tamoxifen 

The American College of Obstetricians and Gynecologists has developed the 

following recommendations for monitoring women on tamoxifen [17];1 

• Perform an annual gynecologic examination. 

• Monitor for symptoms of endometrial hyperplasia or cancer. Women 

should be educated to report any abnormal vaginal symptoms (e.g. , bloody 

discharge, spotting, staining, leukorrhea). 

• Investigate any abnormal vaginal symptoms. 

• Limit tamoxifen use to five years duration because benefit beyond this time 

has not been demonstrated. 

• If atypical endometrial hyperplasia develops, the use of tamoxifen should 

be reassessed and appropriate gynecologic management should be initiated. 

Hysterectomy should be considered for women with atypical endometrial 

hyperplasia in whom tamoxifen therapy must be continued. 

Conclusion 

Endometrial carcinoma is the most common gynecologic malignancy; to date 

there is no rule for screening program in general population. However, high risk 

patient for endometrial cancer have to be evaluated and followed up independently. 

Recommendation and Guidelines for Screening and Prevention of the 

Endometrial Cancer 

Screening 

The committee members (Authors) agreed that from reviewing all the data currently 

available regarding the role of screening for the general population of the women 

for endometrial cancer, it clearly emphasize that there is no role for such screening 

program in detecting early or pre-invasive changes for those women. 

Initiating such screening program using either vaginal ultrasound with or without 

endometrial sampling will not be cost effective, and its effect on the morbidity 

and mortality for those women will be extremely low and will not be beneficial 

for the society. 

Early Detection 

As there is no rule for screening for the general population, the committee members 


agreed that the best approach for such a condition will be the education for the 

general population and for the primary care physician and family physician 

regarding the early symptoms and signs of endometrial cancer. 

Any women who present with post menopausal or Premenopausal bleeding or 

abnormal uterine bleeding should be referred immediately to her gynecologist 

in order for her to do the necessary work-up which must include endometrial 

sampling at least in order to explore the development of hyperplasia or malignancy. 

The committee members agreed that for special sub-group which represent high 

risk for developing endometrial cancer, like those who have history of breast 

cancer and they are on Tamoxifen, or those women with chronic anovulation, they 

should have regular check-up by gynecologist, where they will have ultrasound 

to evaluate the thickness of the endometrial lining according to gynecologist 

assessment and their symptoms and the decision for endometrial sampling will 

be left for the gynecologist according to the patient ultrasound result and her 

symptoms. Also, these women should be aware to report to their physician when 

they have abnormal bleeding and endometrial samples or dilation and curratage 

(D & C) must be done on these patients. 

References 

1. Jemal A, Murray T, Waard W, et al. cancer statistics,2005,CA Cancer J clin 

2005;55:10 

2. Woodruff JD, Pickar JH. Incidence of Endometrial hyperplasia in postmenopausal 

women taking conjugated estrogens [premarin] with medroxyprogesterone acetate 

or estrogens alone. Am J obstetgynecol 1994;170:12-13 

3. Parazzini F, LaVecchia C, Bocciolone L, Franceschi S, The epidemiology of 

endometrial cancer. Gynecol oncol 1991; 41:1-16 

4. Gohen I. Endometrial pathologies associated with postmenopausal tamoxifen 

treatment .Gynecol oncol 2004; 94:256. 

5. Soler M, Chatenoud L, Negri E, etal.Hypertension and Hormone-related 

neoplasm's in women. Hypertension 1999;34:320 

6. Potischman N, Swanson CA, Brinton LA, etal. Dietary association in case-control 

study of endometrial cancer. Cancer Causes Control1993; 4:239. 

7. Xu, WH, Zheng, W, Xiang, VB, etal. Soya food intake and risk of endometrial 

cancer among Chinese women in shanghai: population based case-control study. 

BMJ 2004; 328:1285. 

8. Goodman MT, Wilkens LR, Hankin JH, etal. Association of soy and fiber 

consumption with the risk of endometrial cancer. AMJ Epidemiology 1997;146:294 

9. Goldstein SR, Nachtigall M, Snyder JR, etal. Endometrial assessment by vaginal 

ultrasonography before endometrial sampling in patient with postmenopausal 

bleeding.Am J obstet Gynecol 1990; 163:119. 

10. Karlsson B, Granberg S, Wikland M, etal. Transvaginal ultrasonogrophy of 

the endometrium in women with postmenopausal bleeding. aNordic multicenter 

study . Am J obstet Gynecol 1995; 172:1488. 

11. Neville F. Hacher. 2005. Uterine cancer. Practical gynecology oncology. 

411-429 

12. Koss LG, Schreiber K, Oberlander SG, etal. Detection of endometrial carcinoma 

and hyperplasia in asymptomatic women .Obstet Gynecol 1984, 64:1. 

13. Lu, KH, Dinh M, Kohlmann W, etal. Gynecologic cancer as a sentinel cancer 

for women with hereditary nonpolyposis colorectal cancer syndrome.Obstet 

Gynecol 2005; 105:569. 

14. Aarnio M, Sankila R, Pukkala E, etal. Cancer risk in mutation carriers of 

DNA-mismatch-repair genes.Int J Cancer 1999; 81:214. 

15. Smith RA, Von Eschenbach, AC, Wender R, etal. American cancer society 

guidelines for the early detection of cancer: update of early detection guidelines 

for prostate, colorectal and endometrial cancer.CA Cancer J Clin 2001; 51:38. 

16. Dove-Edwin I, Boks D, Goff S, etal. The out come of endometrial carcinoma 

surveillance by ultrasound scan in women at risk of hereditary nonpolyposis 

colorectal carcinoma and familial colorectal carcinoma. Cancer 2002;94:170 

17. American College of Obstetricans and Gynecologists. Tamoxifen and 

endometrial cancer .AGOG Committee opinion, AGOG2000. 



OVARIAN CANCER 

Faisal Al Safi, FRCSC 1 , Haney Salem 1 , Nashmia Al Mutairi 1 


Corresponding Author: Dr. Faisal Al Safi , FRCSC 

Department of Oncology (Mail Code 1777) 

P.O. Box 22490 Riyadh 11426, Kingdom of Saudi Arabia 


Introduction 

Ovarian cancer remains a highly lethal disease. Although it is the second most 

common female reproductive cancer, preceded by cancer of the uterine corpus, 

more women die from ovarian cancer than from cervical and uterine cancer 

combined. The principle reason for these poor outcomes is the advance stage of 

disease at diagnosis in 70-75% of cases and an overall 5-year survival of only 

20-30%. However, women with a diagnosis of stage 1 disease achieve a 90-95% 

probability of cure (1) 

Risk factors 

The risk of epithelial ovarian cancer increase with age, especially around the 

time of menopause. A family history of epithelial ovarian cancer is one of the 

most important risk factor, infertility and not bearing children are also risk factor, 

while pregnancy and use of birth control pills can decrease the risk of developing 

epithelial ovarian cancer. The risk factors for stromal cell and germ cell tumor 

are unknown (2). 

Pathology 

The majority (90%) of primary ovarian cancer derived from epithelial cells. 

Although they can also arise from other cell type (germ cell tumor,sex cord stromal 

tumor ,and mixed cell type tumor).(2) 

Epithelial ovarian cancer [EOC] constitutes different histological subtype, of which 

serous type is the most prevalent 60% of all EOC. Other type include mucinous, 

endometroid, clear cell, brener, and mixed phenotype tumor, in addition to their 

distant morphological appearance and subtle clinical differences, there is molecular 

evidence for heterogeneity between different EOC subtype [ 3]. 

Clinical symptoms and diagnosis 

The best way to detect early ovarian cancer is to have a high index of suspicion of 

the diagnosis in the symptomatic women, persistent symptoms such as an increase 

in abdominal size, abdominal pain and bloating, fatigue, indigestion, inability 

to eat normally, urinary frequency, pelvic pain, constipation, back pain, urinary 

incontinence of recent oncent, or unexplained weight loss should be evaluated with 

ovarian cancer being included in differential diagnosis. Because ovarian cancer 

occurs most frequently in the postmenopausal women (median age approximately 

60 years), these symptoms should not be ignored. Unfortunately, many clinician 

and patient quick to attribute such symptoms to menopause, aging, dietary changes, 

stress, or functional bowel problems. As a result, delays of weeks or months 

often occur before medical advice is sought or diagnostic studies are performed. 

In evaluating this symptom physical examination including a pelvic examination 

and imaging studies including vaginal ultrasonography may be helpful in making 

the diagnosis. CA125 measurement has not been shown to be useful in most 

circumstances because elevated levels of CA125 are associated with a variety 

of common benign condition .in post menopausal women with a pelvic mass, 

a CA125 measurement may be helpful in predicting a higher likelihood of a 

malignant tumor than a benign tumor, a normal CA125 measurement alone dose 

not rule out ovarian cancer because up to 50% of early stage cancers and 20-25% 

of advance cancers are associated with normal values (1,4 ). 

Treatment 

In contrast to other types of cancer, surgery is always considered for women 

with both localized and advanced ovarian cancer. Surgery is necessary for both 

accurate staging and optimal cytoreduction , and is crucial in successful treatment 

of this disease. The combination of optimal cytoreductive surgery and effective 

chemotherapy has led to significant improvements in survival for women with 

ovarian cancer. (2) 

Screening 

To date, no screening techniques; including CA125 level measurement and pelvic 

ultrasonography, have been proven effective in screening low risk asymptomatic 

women for ovarian cancer.(4) 

For high risk patients, annual gynecologic examination with annual pelvic 

examination is recommended. Hereditary ovarian cancer is estimated to be 

represent only 5-10% of all ovarian cancers. Based on current data, a woman with 

a germ line mutation of BRCA1 or BRCA2 has a life risk of 15-45% of developing 

ovarian cancer. There is no data demonstrating that screening improves early 

detection of ovarian cancer in this population. These women should be offered 

genetic counseling to address issues that relate to their high risk of breast and 

ovarian cancer and the potential impact of these genetic mutations on their offspring. 

Even if this group were screened for ovarian cancer on regular basis, more than 

90% of all potential ovarian cancer patients would remain unscreened. (1) 

Prophylactic salpingo-oopherctomy has been shown to decrease the risk of breast 

as and gynecological cancer in women with inherited risk for these malignancies. 

However, multiple questions remain unanswered regarding this procedure. (5) 

Conclusion 

Ovarian cancer is the most common cause of death in women from gynecological 

malignancy, there is no role of screening test in general population, high risk 

patient need annual gynecologic examination and counseling. 

Recommendations and Guidelines for Screening and Prevention of Ovarian Cancer 

• The committee members ( Authors) ; after reviewing all the current available 

data from most of the studies conducted on the role of screening for a general 

population for ovarian cancer, concluded that there is no place for initiating 

a screening program for the women in the general population as it is proven 

from all the studies conducted on this issue that it will not be cost effective, 

and also its effect on the morbidity and mortality from the disease is very 

limited, as a large number of patient will be unnecessarily screened and 

operated on in order to detect one early case of ovarian cancer. 

• For that reason, the committee members agreed that the best approach is to 

try to identify patients who are at high risk for ovarian cancer. Those women 

should be identified as women with high risk for familial ovarian cancer, 


and counseling should be done for them, and they should be included in a 

screening program designed specifically for the high risk group which will 

include the following: 

1. Annual pelvic examination by a gynecologist; 

2. Annual pelvic ultrasound with colored Doppler for the ovaries; and 

3. Annual CA 125 levels 

• For the very high risk patients who have more than two first degree related 

or one first degree related and two second degree relatives, it is advised 

for those patients to do the BRCA 1 and BRCA 2 study, to counsel those 

patients and advise them regarding the advantage of performing prophylactic 

oophorectomy. 

• The committee members feel that it is very important to educate all 

gynecologists regarding the issue of familial ovarian cancer where it is 

very important to identify the patients at high risk, where they should advise 

the patient regarding enrolment in this screening program, and advise them 

regarding this issue, and their first and second degree relatives for the risk of 

familial malignancies, and encouraging involvement in a screening program. 

References 

1.AGOG committee opinion no280, December2002. 

2. Jonathan S. Berek, Neville F. Haker. Epithelial ovarian cancer.practical 

Gynecologic oncology 2004; 4:443-494. 

3. Scully RE. Pathology of ovarian cancer precursors. J cell Biol 1995, 

23(suppl):208-18. 

4. Jacobs I, Davier AP, Bridges J, etal. Prevalance screening for ovarian cancer 

in post menopsaulal women by CA125 measurement and ultrasonography.BMJ 

1993; 306:1030-1034. 

5. SGO Committee statement on prophylactic salpingo-oophorectomy. Gynecologic 

oncology 98(2005)179-181. 

CERVICAL CANCER 

Faisal Al Safi, FRCSC 1 , Haney Salem 1 , Nashmia Al Mutairi 1 


Corresponding Author: Dr. Faisal Al Safi , FRCSC 




Introduction 

Cervical cancer is the second most common cause of cancer-related morbidity 

and mortality among women in developing countries. It Usually affects women 

between ages of 30 and 55 but has been found as early as the teen years and 

uncommonly after age of 75(1). 

Risk factor 

The major risk factors for cervical cancer include early onset of sexual activity, 

multiple sexual partners, and a high-risk sexual partner (e.g., promiscuous sexual 

activity, sexual exposure to a partner with human papillomavirus infection 

[2]). Other risk factors are a history of sexually transmitted diseases (eg, 

Chlamydia trachomatis, herpes simplex virus) [3], smoking [4], high parity [5], 

immunosuppression, low socioeconomic status, and previous history of vulvar 

or vaginal squamous dysplasia. 

Pathology 

Squamous cell carcinomas (SCCs) account for approximately 80 percent of 

cervical cancers, adenocarcinomas 15 percent, and adenosquamous carcinomas 

3 to 5 percent. Small cell carcinomas and other types are rare (6) 

Clinical manifestations 

Early cervical cancer is frequently asymptomatic, the most common symptoms 

at presentation are: 

• Abnormal vaginal bleeding 

• Post coital bleeding 

• Vaginal discharge that may be watery, mucoid, or purulent and malodorous 

Pelvic or lower back pain, which may radiate along the posterior side of the lower 

extremities, can occur with advanced disease. Bowel or urinary symptoms, such 

as pressure-related complaints, hematuria, hematochezia, or vaginal passage of 

urine or stool, are uncommon and suggest advanced disease. (7) 

Diagnosis 

Diagnosis of cancer is confirmed by biopsy in women with a grossly visible lesion. 

Symptomatic women without a visible lesion and those who have only abnormal 

cervical cytology should undergo colposcopy with directed biopsy or, if necessary, 

diagnostic conization. In addition, any cervix that is unusually firm or expanded 

should be sampled by punch biopsy and endocervical curettage, even if the cervical 

cytology smear does not show evidence of neoplasia. Histologic confirmation of 

invasive cervical cancer is followed by a careful staging evaluation that should 

include a thorough physical examination. The cervix and entire vagina should be 



carefully inspected and palpated to identify overt tumor or subepithelial vaginal 

extension. Rectovaginal examination permits the best assessment of tumor size and 

parametrial involvement. Palpation of the liver and inguinal and supraclavicular 

lymph nodes is important to screen for metastatic disease (7). 

Treatment 

Treatment of invasive cervical cancer involves management of both the primary 

leision and potential site of metastatic disease. Both surgery or and chemo 

radiotherapy may be used for treatment according to clinical stage and risk of 

recurrence. 

HPV Vaccine 

Human Papillomavirus Vaccine (HPV) is a vaccine that prevents infection with 

certain species of Human Papillomavirus associated with the development of 

cervical cancer and genital wart. 

Two HPV Vaccines are currently available: 

Gardasil and Cervarix. Both vaccine protect against two of the HPV types (16, 

18) that cause cervical cancer, and some other genital cancer, Gardasil also protect 

against two of the HPV types (6, 11) that cause genital wart (8). 

Although available data for both vaccines is promising. Still long term efficacy 

and safety is unknown. 

Screening 

Cervical cytology screening programs can detect preinvasive, as well as invasive, 

cellular changes of the cervix. Because cervical cancer typically has a long 

preinvasive state (often a decade or more) and the treatment for preinvasive 

disease is effective, screening programs potentially can prevent the occurrence 

of invasive cervical cancer. [9]. although cervical cancer accounts for relatively 

few deaths in the United States, it is one of the leading causes of cancer death in 

women in developing countries. This observation is thought to be directly related 

to the lack of screening programs in those areas. 

A variety of screening guidelines have been proposed; the choice depends upon 

available resources (11, 12, 13). 

Recommendation and Guidelines for Screening and Prevention of Cervical Ca 

All the committee members (Authors) strongly recommend the initiation of a 

structured, well-organized screening program for cervical cancer among Arab 

women. 

• The design for the program should be suitable and acceptable for our 

community and for the cultural aspects of our women in the Arab World. 

• It is recommended that the screening process should be done by the Pap smear 

using liquid base media in agreement with the international recommendation. 

• The screening process should start one year after the women get married and 

start her sexual activity and the screening should go on in accordance with the 

international recommendation which is once annually, then if the patient has 

three consecutive normal Pap smear, she can do Pap smear every three years. 

• For the high risk population, the screening should continue on annual basis 

in order to prevent any development of invasive disease. 

• Regarding the addition of HPV test to the screening process, the committee 

members feel that a cost effectiveness study should be conducted first in 

order to evaluate the prevalence of the HPV between the Saudi women 

at different age groups, also to determine the sub-groups which are more 

prevalent within our society. 

According to the results of such study, the decision will be made if the 

addition of HPV testing after the age of 30 for those women will be cost 

effective and will be beneficial for them or not. 

• Regarding the issue of vaccination for the Saudi girls between the ages of 

9 to 26, the committee members agreed that this issue should be dealt with 

individually at the current time, as there are many social and economic 

issues connected to it. 

The decision regarding the vaccination should be left to the family regarding 

their choices for the immunization of their daughters after getting all the 

necessary information from their physician. 

The committee members agreed that without the cohort study on the prevalence of 

PHV in Saudi women, the recommendations for vaccinating girls before marriage 

will lack cost effectiveness and benefits before we can get the results of such study. 

References 

1. Parkin DM, Pisani P, Ferlay J. Global cancer statistics .CA cancer J1999; 49:33. 

2. Castellsage X, Bosch X, Munoz N, etal. Male circumcision, penile human 

papillomavirus infection, and cervical cancer in female partners. N Engl J Med 

2002; 346:1105. 

3. Hawes SE, Kiviat NB, Are genital infections and inflammation cofactors in 

the pathogenesis of invasive cervical cancer?.J Natl cancer inst 2002; 94:1592. 

4. Catle PE, Wacholder S, Lorincz AT. etal. A prospective study of high grade 

cervical neoplasia risk among human papilloma virous-infected women. J Natl 

cancer inst 2002; 94:1406. 

5. Munoz N, Franceschi S, etal. Role of parity and HPV in cervical cancer: the 

IARC multicenter case-control study.Lancet 2002; 359:1093. 

6. Alboes-saavedra J, Gersell D, etal. Terminology of endocrine tumors of 

the uterine cervix: results of a worshop sponsored by the collage of Amirican 

pathologists and the National cancer insutute.Arch pathol lab med 1997; 121:34. 

7. Jonathan S. Berek, Neville F. Haker. Cervical cancer. Practical Gynecologic 

oncology.2004; 4:337-372. 

8. Cummins J. Recombinant Cervical Cancer Vaccines, Science in Society 29; 

20-21, 2006 

9. Womack Warren AY. Achievable laboratory standards: a review of cytology of 

99 women with cervical cancer. Cytopathology 1998; 9:171. 

10. Saslow D, etal. American Cancer Society Guidelines for the Early Detection 

of Cervical Neoplasia and Cancer. CA Cancer J Clin 2002; 52:342-362 

11. USPSTF. Screening for Cervical Cancer. Jan 2003. 

12. ACOG. Cervical Cytology Screening. ACOG Practice Bulletin no. 45. ACOG 

2003;102: 417-427 


ESOPHAGEAL CANCER 

Abdul-Rahman Jazieh, MD, MPH, Omalkhair Abulkhair, MD 

King Abdulaziz Medical City for National Guard, Riyadh, KSA 

Corresponding Author: Abdul Rahman Jazieh, MD, MPH 

Department of Oncology (Mail code 1777) 


E-mail: jazieha@ngha.med.sa 

Introduction 

Esophageal cancer is a common cancer which has poor prognosis with a five year 

survival of less than 15%. Although squamous cell cancer is the most common 

histologic subtype, adenocarcinoma is increasing rapidly. 

This manuscript will present the epidemiology and risk factors of esophageal 

cancer and review early detection and prevention of related issues. 

Epidemiology 

Esophageal cancer ranks 6th among cancers worldwide (constitutes 5.7% of 

all cancer mortality). It does increase with age with peak between age 50 – 70. 

(Globocan 2002). Esophageal cancer is more common in male; with male to 

female ratio of 3-5:1. 

Risk Factors 

Smoking and Alcohol 

Smoking and alcohol are major risk factors for esophageal cancer (UTD 14 – 15). 

Smoking does not only increase the risk of squamous cell carcinoma but also 

increase the risk of adenocarcinoma especially in patients with Barretts esophagus 

as the risk is about 2.4 times higher that non smokers (UTD 13). 

Gastroesophageal Reflux and Barrett’s Esophagus 

Gastroesophageal reflux is a major risk factor for adenocarcinoma as the risk of 

esophageal cancer increases significantly in patients with GE reflux. The odd ratio 

of having esophageal cancer is more than 7 times for patients with reflux symptoms 

which may increase to more than 40 times if the symptom is long standing for 

more than 20 years (79-80). 

Underlying Esophageal Diseases 

Such achalasia and caustic esophageal injury increases the risk of esophageal 

cancer (43, 44). 

Obesity and Dietary Risk Factors 

Eating or drinking hot food or drinks may cause increase in the risk of esophageal 

cancer e.g. hot tea (29), food that contains U-nitroso may increase the risk of 

esophageal cancer so is the consumption of Betel nuts. 

Furthermore, low selinum and zinc diets have been implicated in increasing the 

risk of esophageal cancer. Obesity with BMI between 25 – 30 kg/m2 increase the 

odd ratio of esophageal cancer by 1.5 and if the BMI was more than 30 kg/m2, 

the odd ratio increased to 2.7 (83,84). 

Medication Use 

The use of oral biphosphenate and medications that decrease the lower esophageal 

sphincter (e.g. nitroglycerine, aminophyllin) increase the risk of esophageal cancer. 

Presenting Sign and Symptoms 

The symptoms of esophageal cancer result from the obstructive lesion that causes 

dysphagea especially of the solid food, odanophagea, regungitation, etc. These 

may lead into anorexia and weight loss. 

Patient may develop respiratory symptom due to aspiration or tracheoesophageal 

fistula. Chroninc blood loss or frank bleeding will lead to anemia and its associated 

symptoms. 

Screening 

There is no study demonstrated the value of mass screening for esophageal cancer. 

Management of Esophageal Cancer 

Early esophageal cancer is managed by surgical resection and combined 

multidiscipline treatment with radiation therapy and/or chemotherapy. 

Advanced stages are usually non curable and the goal of care will be to alleviate 

the obstructive symptoms. 

Prevention 

Avoidance of alcohol and smoking is paramount to decrease the risk of esophageal 

cancer. Treating esophageal reflux would help to increase fiber intake may have 

protective value. 

Esophageal Cancer Prevention 

Primary Prevention 

• Avoid smoking and alcohol consumption. 

• Treat esophageal reflux. 

Public Screening 

• No evidence of benefit for public screening. 

Reference 

1. Globocan 2002: http://www.dep.iarc.fr 



LUNG CANCER PREVENTION AND EARLY DETECTION 

Abdul-Rahman Jazieh, MD, MPH 






Abstract 

Lung cancer is the most common cancer in incidence and mortality worldwide. 

Most lung cancer cases are attributed to tobacco use which makes it very amendable 

to preventative interventions. 

Although there is no proven benefit of mass screening for lung cancer, large study 

about the role of spinal CT scan is ongoing. Smoking cessations and avoidance of 

other known risk factors will reduce the risk of lung cancer significantly. 

This manuscript discusses the epidemiology of lung cancer, its risk factors and 

the value of early detection and prevention. 

Introduction 

Lung cancer ranks first in the world in incidence and mortality. Multiple risk 

factors have been identified and the majority of lung cancer cases are preventable. 

This manuscript presents summary of the epidemiology of lung cancer and risk 

factors and reviews its prevention and early detection recommendations. 

Epidemiology 

Lung cancer is the most common cancer worldwide (1.35 million of 10.9 million 

of new cases) and the deadliest cancer (1.18 million of 6.7 million cancer-related 

deaths).(1) 

As per the Saudi National Cancer Registry 2004 statistics, there were 296 cases of 

lung cancer accounting for 4.2% of all diagnosed cases.(2) Lung cancer ranked 

fourth among male population and sixteenth among female population. It affected 

233 (78.7%) males and 63 (21.3%) females with male to female ratio of 3.7:1. The 

overall Adjusted Standard Rate (ASR) was 3.1/100,000. ASR was 5.5/100,000 

for males and 1.5/100,000 for females, which is much less than the Western 

figures. For example, ASR in the United States is 85.7/100,000 for males and 

54.2/100,000 for females. The mean age at diagnosis was 64 years among males 

(range 24-98 years) and 61 years among females (range 24-89 years). The most 

common morphological subtypes are squamous cell carcinoma, adenocarcinoma 

and small cell lung cancer Stage distribution showed that 55.7% are having distant 

metastasis at presentation, and localized disease, regional and unknown represent 

13.2%, 10.8% and 20.3%, respectively. 

Pathology 

Lung cancer is divided into non-small cell lung cancer (more than 80% of 

cases) and small cell lung cancer. The non-small cell lung cancer is divided into 

adenocarcinoma, squamous cell and large cell carcinoma. 

There was a shift in the incidence of squamous cell carcinoma and adenocarcinoma. 

Up to the late 1980, squamous cell lung cancer was the most common subtype, 

which was then surpassed by adenocarcinoma. 

It is note worthy that the risk of all of these subtype of cancer including 

adenocarcinomas is increased by smoking. This is contrary to the thought of some 

practitioners that adenocarcinoma risk does not increase by smoking which is driven 

by the fact the adenocarcinoma is the most common sub-types in non-smokers. 

Risk Factors for Lung Cancer 

a. Smoking 

The rapid increase of lung cancer over the last century from a rare disease 

to an epidemic is attributed to the exposure to newly introduced major risk 

factors, which include smoking at the top of the list. Around 85-90% of lung 

cancer cases could be attributed to the use of tobacco, directly or indirectly. (3) 

The relative risk of developing lung cancer is 11 – 20 times more in smokers 

compared to non-smoker. The risk of lung cancer is dependent on the number 

of cigarette smoked per day (calculated by pack/year number) and the duration 

of smoking with increase in risk of smoking started at younger age. (4 - 6) 

For example, 35 year old man has a 9% chance of dying from lung cancer 

before age 85 if he smokes less than 25 cigarettes per day. This risk increases 

to 18% if he smokes more than 25 cigarette per day. (7) 

The environmental tobacco exposure (ETS), which may be referred to as 

“second hand smoking”, increases the risk by 27-80%. (8 - 11) ETS may occur 

at home or at work. For example, the risk of non-smoker spouse increases by 

20 – 30% if the spouse is smoker over non-smoker’s spouse. (12,13) About 

25% of the lung cancer in non-smoker is attributed to second hand smoking 

which constitutes about 5% of all lung cancer cases. 

b. Radon Gas 

The exposure to radon is an established risk factor of lung cancer, which 

was initially observed in uranium miners. (14, 15) However, this naturally 

occurring radioactive gas is a delay product of uranium – 238 and radium – 

226 and accumulates also in buildings and homes especially in basements 

and lower level floors. 

The exposure to the indoor radon may be responsible for up to 9% if lung 

cancer in Western countries and it has synergistic effect with smoking. 

Smoking in miners increases the risk of lung cancer by 10 times over the 

non-smoker miners.(16) 

c. Industrial and Occupational Exposure 

Exposure to various carcinogens has been linked to lung cancer. The list of 

these carcinogens includes: arsenic, polycyclic hydrocarbons, diesel exhaust, 

herbicides and insecticides, silica, asbestos, beryllium and chromium. 

Asbestos is well known cause of not only mesothelioma but also of primary 

lung cancer. The risk of exposure to asbestos is about 5 times more than 

the general population but when it is combined with smoking, a synergetic 

effect takes place and increases the risk up to 50 – 100 times. The incidence 

peak of cancer occurs 25 – 30 years after exposure. (17 - 21) 

d. Air Pollution 

Exposure to outdoor pollution, especially nitrogen oxides from the traffic 

fumes has been linked to increase risk of lung cancer. (10, 22) 


e. Other Risk Factors 

There are other risk factors that were associated with increase incidence 

of lung cancer including family history, sedentary life, alcohol and dietary 

factors with variable strength of association. (23 - 26) 

Presenting Signs and Symptoms 

Patients with lung cancer present with three categories of manifestations like most 

solid tumors (27 - 28) The first type is related to the mass effect of the primary 

tumors including: cough, chest pain, shortness of breath and hemophysis, postobstructive 

pneumonia and superior vena cava syndrome. 

The second type is related to distant metastatic lesions which may include 

seizure, pathologic fracture, lymphadenopathy or organomegaly. The third type 

of manifestations is related to systemic paraneoplastic manifestations not related 

to the mass effect per se which include: hypercalcemia, hyponateremia, cushing 

syndrome, neurological manifestation, weight loss, or digital clubbing (hypertrophic 

pulmonary osteoarthropathy). 

Management of Lung Cancer 

The management of lung cancer should be based on multidisciplinary team 

approach. The treatment is usually stage dependent. For early stages I, II and 

selected III: surgery is the main approach. Adjuvant chemotherapy is helpful in 

resected stages II and III but not stage I. 

For stage III A/B which is considered locally advanced disease, treatment is 

usually combined chemotherapy and radiotherapy with surgical intervention in 

selected cases. For metastatic disease: systemic therapy using chemotherapy or 

biological therapy is the standard approach. 

Prognosis and Outcome 

The prognosis of lung cancer is stage dependent with higher survival rates for 

earlier stages. The 5 years survival for stages ranges from 67% for stage I to less 

than 1% in stage IV. (32) 

Therefore, the earlier the cancer is discovered, the better the chance of survival. 

Hence, the importance of identifying an effective screening methods would be 

of great value. 

Screening and Early Detection 

Various studies using chest x-ray, sputum cytology and spinal CT scans were not 

supportive of routine mass screening. (29 - 31) A large multisite National Cancer 

Institute-USA sponsored study of spinal CT scan including more than 50,000 

participants may help answer this question. 

Prevention 

Smoking cessation at any age is of proven benefits of reduction of lung cancer 

risk over extended period of time (15 – 20 years) but it remains higher than never 

smoker risk. (8, 34 - 35) 

If smoker cannot quit completely, reducing the number of cigarette smoked may 

reduce the risk of cancer. (36) Smoking cessation and eliminating the risk of 

tobacco will eradicate the majority of lung cancer cases making it one of the most 

preventable cancer. (8, 35, 37) It is imperative to have a systemic campaigns or 

tobacco control programs that ban public advertising and promotions, especially 

those which targets the youth and that ban smoking in public areas such as 

restaurants or workplace. (38 - 44) Minimizing the occupational exposure to 

the above mentioned carcinogens will decrease the risk for lung cancer further. 

Conclusion 

While lung cancer is the leading cancer in incidence and mortality, it is also a 

preventable disease in the majority of cases. 

Recommendations for Early Detection and Prevention for Lung Cancer 

Primary Prevention: 

• Cancer prevention is highly recommended by avoiding tobacco products 

(including cigarettes, cigars, chewing tobacco, arkila or shisha and passive 

indirect smoking) smoking cessations and avoiding environmental tobacco 

exposure and exposure to other known risk factors. 

• Stopping all forms of tobacco promotion and advertising is a major component 

of lung cancer prevention. 

Early Detection: 

• No method was proven efficacious in early detection of lung cancer that 

translated into better survival. 

References 

1. Parkin D, Bray F, et al. Global cancer statistics 2002. Ca Cancer J 2005;55:74- 

108. 

2. National Cancer Registry, 2004. Kingdom of Saudi Arabia. 

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a special emphasis on cigarette smoking. Environ Health prospect 1995:103; 

131-142. 

4. Doll R, Peto R, Boreham J, et al. Mortality from cancer in relation to smoking: 

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5. Doll R, Peto R. Cigarette smoking and brochial carcinoma: dose and time 

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6. Wiencke JK, Thurston SW, Kelsey KT, et al. Early age at smoking initiation and 

tobacco carcinogen DNA damage in the lung. J Natl Cancer Inst 1999;91:614-9. 

7. Mattson ME, Pollack ES, Cullen JW. What are the odds that smoking will kill 

you? Am J Public Health 1987; 77:425-31. 

8. Crispo A, Brennan P, Jockel KH, et al. The cumulative risk of lung cancer among 

current, ex- and never-smokers in European men. Br J Cancer 2004;91:1280-6. 

9. Miller DP, De Vivo I, Neuberg D, et al. Association between sel-reported 

environmental tobacco smoke exposure and lung cancer: modification by GSTP1 

polymorphism. Int J Cancer 2003; 104: 758-63. 

10. Vineis P, Airoldi L, Veglia F, et al. Environmental tobacco smoke and risk of 

respiratory cancer and chronic obstructive pulmonary disease in former smokers 

and never smokers in the EPIC prospective study. BMJ 2005; 330:227. 

11. Wen W, Shu XO, Gao YT, et al. Environmental tobacco smoke and mortality 

in Chinese women who have never smoked: prospective cohort study. BMJ 

2006;333:376. 

12. Fontham ET, Correa P, Reynolds P, et al. Environmental tobacco smoke and 

lung cancer in nonsmoking women. A multicenter study. JAMA 1994; 271:1752-9. 

13. Alberg A, Samet J. Epidemiology of lung cancer. Chest 2003;123:21S-49S. 

14. IARC. Ionizing radiation, part 2: some internally deposited radionuclides. Views 

and expert opinions of an IARC working group on the evaluation of carcinogenic 



risks to human. Lyon, 14 – 21 June 2000. IARC Monogr Eval Carcinog Risks 

Hum 2001; 78:1-559. 

15. Frumkin H, Samet JM. Radon. CA Cancer J Clin 2000:51:337-44. 

16. Darby S, Hill D, Auvinen A, et al. Radon in homes and risk of lung cancer: 

collaborative analysis of individual data from 13 European case-control studies. 

BMJ 2005;330:223. 

17. Hammond EC, Selikoff IJ, Seidman H. Asbestos exposure, cigarette smoking 

and death rates. Ann N Y Acad Sci 1979; 330:473-90. 

18. Berry G, Lidell FD. The interaction of asbestos and smoking in lung cancer: 

a modified measure of effect. Ann Occup Hyg 2004; 48:459-62. 

19. Chen TM, Kuschner WG. Non-tobacco related lung carcinogens. Lung cancer 

principle and practice. Harvey pass et al. Lippincot Williams and Wilkins, Third 

edition, 2005:61-73. 

20. Lee PN. Relation between exposure to asbestos and smoking jointly and the 

risk of lung cancer. Occup Environ Med 2001;58:145-53. 

21. Lidell FD. The interaction of asbestos and smoking in lung cancer. Ann Occup 

Hyg 2001; 45:341-56. 

22. Nafstad P, Haheim LL, Wisloff T, et al. Urban air pollution and mortality in a 

cohort Norwegian men. Environ Health Perspect 2004; 112:610-5. 

23. Liu Y, Sobue T, Otani T, et al. Vegetables, fruit consumption and risk of lung 

cancer among middle-aged Japanese men and women: JPHC study. Cancer 

Causes Control 2004; 15:349-57. 

24. Freudenheim JL, Ritz J, Smith-Warner SA, et al. Alcohol consumption and risk of 

lung cancer: a pooled analysis of cohort studies. Am J Clin Nutr 2005; 82:657- 67. 

25. Tardon A, Lee WJ, Delgado-Rodriguez M, et al. Leisure-time physical activity 

and lung cancer: a meta-analysis. Cancer Causes Contro 2005; 16:389-97. 

26. Nitadori J, Inoue M, Iwasaki M, et al. Association between lung cancer 

incidence and family history of lung cancer: data from a large-scale populationbased 

cohort study, the JPHC study. Chest 2006; 130: 968-75. 

27. Spiro SG, Gould MK, Colice GL. Initial evaluation of the patient with lung 

cancer: symptoms, signs, laboratory, tests and paraneoplastic syndromes. 

ACCP Evidenced-Base Clinical Practice Guidelines (2nd Edition) Chest 2007; 

132:149S-160S 

28. Scagliotti G. Symptoms, signs and staging of lung cancer. Eur Respir Mon 

2001; 17:86-119 

29. Henschke CI, McCauley DI, Yahkelvitz DF, et al. Early Lung Cancer Action 

Project: overall design and findings from baseline screening. Lancet 1999; 

354:99-105. 

30. Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose 

spiral computed tomography. Am J Resp Crit Care Med 2002; 165:508-513. 

31. Bach FH, Kelley M, Tate RC, et al. Screening for lung cancer: a review of the 

literature. Chest 2003; 123:72S-82S. 

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Chest 1997; 111:1710-7. 

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Clin North Am 1992; 76:305-31. 

34. Halpern MT, Gillespie BW, Warner KE. Patterns of absolute risk of lung cancer 

mortality in former smokers. J Natl Cancer Inst 1993;85:457-64. 

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in UK since 1950: combination of national statistics with two case-control studies. 

BMJ 2000;321: 323-9. 

36. Godtfredsen NS, Prescott E, Osler M. Effect of smoking reduction on lung 

cancer risk. JAMA 2005; 294:1505-10. 

37. Ebbert JO, Yang P, Vachon CM, et al. Lung cancer risk reduction after smoking 

cessation: observations from a prospective cohort of women. J Clin Oncol 2003; 

21:921-926. 

38. Homan CD, Donovan RJ, Corti B, et al. Banning tobacco sponsorship: replacing 

tobacco with health messages and creating health-promoting environments. Tob 

Control 1997;6:115-21. 

39. Farelly MC, Evans WN, Sfekas AE. The impact of workplace smoking bans: 

results from a national survey. Tob Control 1999;8:272-7. 

40. McVey D, Stapleton J. Can anti-smoking television advertising affect smoking 

behaviour? Controlled trial of the Health Education Authority for England’s antismoking 

TV campaign. Tob Control 2000;9:273-82. 

41. Wakefield M, Chaloupka F. Effectiveness of comprehensive tobacco control 

programmes in reducing teenage smoking in the USA. Tob Control 2000;9:177-86. 

42. Braverman MT. Adolescent smoking and exposure to tobacco marketing under 

a tobacco advertising ban: findings from 2 Norwegian national samples. Am J 

Public Health 2004;94:1230-8. 

43. Shields M. Smoking bans: influence on smoking prevalence. Health Rep 

2007;18:9-24. 

44. Bala M. Strzeszynski L, Cahill K. Mass media interventions for smoking 

cessation in adults. Cochrane Database Syst Rev 2008; 23:(1): CD004704. 


ORAL MALIGNANCIES: 

ROLE OF PREVENTION AND EARLY DETECTION 

Dr. Abdulaziz Binahmed 

King Abdulaziz Medical City, Riyadh 

Corresponding Author: Dr. Abdulaziz Binahmed, BDS, MDent, MSc, FRCDC 

Consultant, Department of Surgery, King Abdulaziz Medical City 


Assistant Professor, Department of Surgery 

University of Manitoba, Winnipeg, Canada 

E-mail: azizbinahmed@mac.com 

Introduction 

The oral cavity is that part of the upper aerodigestive tract which extends from the 

mucocutaneous junction at the vermillion border of the lip to the anterior surface 

of the faucial arch. It is lined by squamous epithelium containing interspersed 

minor salivary glands and it also contains dento-alveolar structures that support 

the upper and lower dentition. Primary tumors of the oral cavity may arise from 

the surface epithelium, minor salivary glands or submucous soft tissue as well as 

from dental structure, bone or neurovascular tissue. Squamous cell carcinoma of 

the oral cavity forms more than 90% of all newly diagnosed cases of oral cancer, 

with the majority of patients being males. A rising incidence has been observed in 

females over the past 50 years. Anatomical sites in the oral cavity that have been 

described by the International Union Against Cancer (UICC)/ American Joint 

Committee on Cancer (AJCC) Staging System are the tongue, floor of mouth, 

gingiva, buccal mucosa, retromolar trigone and hard palate. The tongue and the 

floor of mouth are the most common sites of origin for primary squamous cell 

carcinoma in the oral cavity in the Western World. In other parts of the world 

e.g. Middle East and Asia, the retromolar trigone and buccal mucosa are the most 

frequently encountered primary sites due to tobacco chewing and the chewing 

of betel nuts. Despite controversy and debate during the last century between 

different health care disciplines regarding the best treatment of oral cancer using 

radiation, surgery or chemotherapy, surgery still plays a primary role in the control 

of the disease. 


Oral cavity cancers account for about 3% of all cancers diagnosed each year in 

north America. (1,2) This is estimated to be 27,000 newly diagnosed cases in the 

United States and 3,200 cases in Canada. Slightly more than 10,000 Americans 

and 1,000 Canadians will die of oral cancer each year. Studies from around the 

globe show that for both sexes combined cancer of the mouth and pharynx ranks 

sixth overall behind lung, stomach, breast, colon, rectum and cervix uteri in that 

order. The rates range from a low of 1.8/100,000 per year to a high of 47/100,000 

per year. The highest rates of oral cancer in the world are found in France, the 

Indian subcontinent, Brazil and central/eastern Europe. There are also marked 

differences between countries in the same geographic regions. 

The incidence of oral cancer increases with age in all parts of the world. In the West, 

98% of the patients are over 40 years of age. In the high prevalence areas of the world, 

many of the patients are less than 35-years-old owing to heavy usage of various 

forms of tobacco. Furthermore, it is now clear that in many Western countries, 

there has been an alarming rise in the incidence of oral cancer during the past two or 

three decades particularly among younger men a trend that appears to be continuing. 

In industrialized countries, men are affected two to three times as often as women. 

The most important risk factors are alcohol and tobacco consumption for intraoral 

cancer and sun exposure for lip cancer in those who work outdoors. The incidence 

of tongue and other intraoral cancer for woman can be greater or equal to that of 

men in high incidence areas such as India where chewing tobacco is also common 

among women. There has been a gradual increase of the number of female patients 

reflected by the change in male to female ratio in the Western societies. 

The reported head and neck cancer cases in Saudi Arabia by the National Cancer 

Registry for the year 2002 was approximately 700 new cases, (3) and we believe 

that this number is increasing annually as the aging population is increasing. 

Risk Factors 

Tobacco 

There is absolutely no doubt that on a global scale the use and abuse of tobacco 

products is the major cause of oral cancer. Typically 90% of men and 60% of 

women with oral carcinomas use tobacco. The incidence rate of oral carcinoma 

in smokers is six to ten times greater when compared to non-smokers. 

Alcohol 

It is very difficult to separate the effects of alcohol and tobacco as most heavy 

alcohol consumers also use tobacco. Nevertheless, some cohort and case control 

studies have found an increased risk of upper aerodigestive tract cancer associated 

with alcohol drinking in non-smokers. The epidemiological evidence shows that 

all of alcoholic drinks are dangerous if heavily consumed. 

Viruses 

The knowledge of viruses as a human carcinogen has improved in the past two 

to three decades. Viruses contribute to the multi-step process of carcinogenesis 

in many human neoplasms. Human papilloma virus, especially human papilloma 

16, is the most common type associated with both cervical and oral cancer. In 

vitro studies show that high-risk HBV types can immortalize primary human 

oral epithelial cells. 


The common presenting symptoms include pain, oral ulcer, oral mass, and neck 

mass. While the common presenting signs include leukoplakia, erythroplakia, 

exophytic mass, oral ulcer and neurological alterations. 

Outcome & Prognosis 

Despite the improvements in surgical and radiotherapeutic techniques, intraoral 

squamous cell carcinoma has relatively unfavorable prognosis with an overall 

five-year survival rate of 35 – 50%. The survival rate has regrettably remained 

virtually unchanged over the past three decades. The increase in the incidence 

of oral cancer accentuates this mortality from the cancer. 

Several parameters have been adapted and applied by clinicians to evaluate the 

prognosis of oral cancer. These parameters can be divided into epidemiological 

parameters which include age, sex, race, alcohol and tobacco intake and 

comorbidity; clinical parameters which include the TNM classification, stage, 

and the site of the primary tumor; and histological parameters which include the 

marginal status, the perineural or perivascular invasion, histopathological grading, 

tumor thickness and extracapsular spread. 



The single most important factor affecting long-term results after treatment of 

carcinoma of the oral cavity is the stage of the disease at the time of presentation. 

For early stage tumors excellent cure rate is achieved. The five year survival rate 

for patients with oral cancer treated at Memorial Sloan-Kettering Cancer Center 

between 1986 and 1995 showed that for Stage I oral cancer the five year diseasespecific 

survival was more than 90% while for Stage II, III, IV 80%, 65%, 55%, 

respectively. The overall survival in the same center was site dependent; with 

tumors in the buccal mucosa and retromolar trigone having the worst outcome. (4) 

Magnano et al(5,6) found that the T stage was a consistent and dependent predictor 

of pathologically involved cervical lymph nodes. In addition, maximal tumor 

diameter has been shown to predict local recurrence in tumors arising from the 

lower lip, oral cavity and oropharynx. Pernot in 1996 reported on 565 patients in 

which he showed that the five-year survival for patients with T1 lesion was 70% 

compared to 29% in patients with T3 disease(7). 

It is not surprising that the presence of clinically positive lymph nodes at the time 

of presentation is probably the single most important factor in determining the 

outcome and prognosis. In general patients presenting with neck node metastases 

do half as well as patients who present with a primary tumor only. Jones et al(8) 

performed a univariate and multivariate analysis of a number of tumor factors 

and prognosis in oral cancer on 524 patients. Their study showed that only the T 

stage and the N stage were significant as predictors for survival. 

Mamelle et al(9) reviewed 914 patients and his multivariate analysis showed that the 

number of positive nodes was a significant and independent predictor of survival. 

Olsen et al(10) has shown that the number of positive lymph nodes reflects the 

prognosis and overall survival in 284 patients that he studied. This information is 

in agreement with a study that Shah(11) performed on 704 patients showing that 

the failure rate was significantly higher as the number of positive nodes increased. 

Screening Methods Overview 

A routine Head and neck examination in any patient above the age of forty who has 

any of the risk factors mentioned earlier. A focused oral examination is mandatory 

with proper inspection and palpation of all the high-risk areas in high risk patients. 

Prevention 

Primary prevention is the approach that concentrates on eliminating the risk factors. 

Educating the public on these risk factors is the first step in primary prevention. 

Although educating the primary health care providers on approaches to eliminate 

or at least reduce risk factors such as smoking and alcohol consumption. 

Secondary prevention is the approach that concentrates on early detection of the 

disease (Screening). In oral cancer, this approach is preformed via routine clinical 

and oral examination for high risk patients (Smokers, >40 years, Alcohol, Poor 

Diet) as general public screening in oral cancer is not cost effective. 

Tertiary prevention is the approach that focus on reducing recurrence of the treated 

disease or minimize treatment morbidity. 

Recommendations for Early Detection and Prevention for Head and Neck 

Primary Prevention: 

• Cancer prevention is highly recommended by avoiding tobacco products 

by smoking or chewing. 

• Avoiding alcoholic drinks. 


• No method was proven efficacious in early detection of oral cavity cancers. 

• Good clinical exams for high-risk patients; smokers older than 40 years, 

alcohol consumption and poor nutrition. 

References 

1. Jemal A, Murray T, Samuels A, et al: Cancer statistics, 1999. CA Cancer J 

Clin 53:5,2003. 

2. Canadian cancer statistics 2004. 

3. Cancer Incidence Report, Saudi Arabia, 2002. National Cancer Institute. 

4. Shah JP. Head and neck surgery, 2nd ed. London: Mosby-Wolfe, 1996: 189-196 

5. Magnano M, De Stefani A, Lerda W, Usai A, Ragona R, Bussi M, Cortesina G. 

Prognostic factors of cervical lymph node metastasis in head and neck squamous 

cell carcinoma. Tumori. 1997 Nov-Dec;83(6):922-6. 

6. Magnano M, Bongioannini G, Lerda W, Canale G, Tondolo E, Bona M, Viora 

L, Gabini A, Gabriele P. Lymphnode metastasis in head and neck squamous cells 

carcinoma: multivariate analysis of prognostic variables. J Exp Clin Cancer Res. 

1999 Mar;18(1):79-83 

7. Pernot M, Hoffstetter S, Peiffert D, Aletti P, Lapeyre M, Marchal C, Luporsi 

E, Bey P, Nancy VL. Role of interstitial brachytherapy in oral and oropharyngeal 

carcinoma: reflection of a series of 1344 patients treated at the time of initial 

presentation. Otolaryngol Head Neck Surg. 1996 Dec;115(6):519-26. 

8. Jones AS. Prognosis in mouth cancer: tumor factors Eur J Cancer B Oral 

Oncol. 1994 Jan;30B(1):8-15. 

9. Mamelle G, Pampurik J, Luboinski B, Lancar R, Lusinchi A, Bosq J. Lymph 

node prognostic factors in head and neck squamous cell carcinomas in patients 

with lymph node involvement. Am J Surg. 1994 Nov;168(5):494-8. 

10. Olsen KD, Caruso M, Foote RL, Stanley RJ, Lewis JE, Buskirk SJ, Frassica 

DA, DeSanto LW, O'Fallon WM, Hoverman VR Primary head and neck cancer. 

Histopathologic predictors of recurrence after neck dissection. . Arch Otolaryngol 

Head Neck Surg. 1994 Dec;120(12):1370-4. 

11. Shah JP, Cendon RA, Farr HW, Strong EW. Carcinoma of the oral cavity. 

factors affecting treatment failure at the primary site and neck. Am J Surg. 1976 

Oct;132(4):504-7. 


URINARY BLADDER CANCER 

Dr. Alaa Kandil 1 

(1) Alexandria School of Medicine, Alexandria, Egypt 

Corresponding Author: Dr. Alaa Kandil 

Professor of Clinical Oncology, Alexandria School of Medicine 

Alexandria, Egypt 

E-mail ad: alaakandil@hotmail.com 

Bladder cancer is the second most common genitourinary malignancy. The 

American Cancer Society estimated that 61,420 new cases of bladder cancer 

would be diagnosed in the United States during 2006 and about 13,060 individuals 

would die of the disease.(1) 

Many patients with bladder cancer experience recurrence but do not die of the 

disease. While bladder cancer is only the fourth most common cancer in men after 

lung, colorectal and prostate cancers, in terms of incidence it is the second most 

prevalent malignancy in middle-aged and elderly men after prostate cancer.(2),(3) 

The current standard of care for detecting and monitoring bladder tumors is 

cystoscopy, voided urine cytology and imaging.(4) 

However, cystoscopy is invasive, painful and costly. Therefore, it is not suitable as a 

screening test. Although urine cytology is a noninvasive test, it is limited by its low 

sensitivity of 20% to 40% for low grade tumors. Several methods have been reported 

for the early detection of bladder cancer using various potential markers. (5– 8) 

The specificity and sensitivity of these tests vary between 50% and 100%. Therefore, 

they are not adequate for screening patients. Ideally a urine based bladder tumor 

marker would be noninvasive, inexpensive and nonuser dependent, and have 

high accuracy. Optimal markers would serve for screening, initial diagnosis, and 

monitoring recurrence and progression as well as predicting prognosis. 

The criteria defined by Wilson and Junger for assessing the performance of a 

screening program appear suitable to use when discussing the role of a urinarybased 

assay for bladder cancer (BCa) [9]. 

These criteria can be divided into those related to the population involved, the 

disease being studied, the test used, and the health economic consequences of 

screening. 

It must first be stated that population screening for BCa, even with a noninvasive 

urinary-based test, is unlikely to be cost effective or to produce significant reductions 

in mortality. At least two well-described population screening programs have been 

reported and in both the overall incidence of BCa was 1.2–1.3% [10, 11-13]. 

Of these few cases, around 45% were high grade and half of these already had 

muscle invasion. Thus, the capacity to improve outcomes using screening in the 

general population is low, given the few patients with early invasive tumours. 

However, populations at high risk of BCa can be defined because many etiologic 

risk factors are known. For example, cigarette smoking increases the risk of BCa 

4-fold and occupational exposure to chemical carcinogens may account for 20% 

(or more) of all tumours [14]. 

Targeting high-risk populations with BCa screening could produce significant 

reductions in mortality at a frequency to justify the expense. The majority of use for 

a urinary assay for BCa would be in surveillance for patients previously diagnosed 

with the disease. These patients are compliant (because they are anxious about 

their disease state) and would welcome the replacement of invasive cystoscopic 

examination. 

For a screening or surveillance test to be beneficial it must identify the disease 

at a stage where treatment significantly improves the prognosis. A urinary-based 

assay that can diagnose BCa whilst confined to the urothelium or carcinoma in 

situ could fulfil this criterion. However, the majority of bladder tumors belong to 

the noninvasive phenotype. 

For these tumours early diagnosis, before the onset of symptoms, is unlikely to 

alter overall survival rates, even if it does reduce recurrence rates and morbidity (by 

treating lower-volume cancers). It is mainly tumors of the invasive pathway (around 

25–33% of all BCa) that would benefit from early diagnosis and treatment. In these 

cancers a clear relationship exists between stage at diagnosis and outcome[15,16] 

in a patient presenting with symptoms. Although evidence suggests this relationship 

persists in a screened [10] population, studies suggest it may not hold true in 

surveyed patients [17]. 

Table 1: Current evaluated urinary assays for bladder cancer 

Category Target Function Sensitivity Specificity 

Soluble - Haemoglobin/ Oxygen carriage 50-100% Poor 

urinary red 

Proteins blood cells 

- Complement 

Immune system 50-100% 64-100% 

factor H- Nuclear structure 50-100% 75-90% 

related protein 

- NMP-22 Nuclear structure 

- BLCA-1 protein 

- BLCA-4 Nuclear structure 96% 100% 

- Survivin protein 

- Cytokeratins Antiapoptotic 100% 87-100% 

8,18,19,20 protein 

- Hyaluronic Cytoskeletal 82-87% 55-70% 

acid and - structure 

hyaluronidase Glycosaminoglycan 88-94% 84% 

Cancer 

cell-based 

assays 

- Cytology 

- microsatellite 

analysis 

- Telomerase 

- DNA 

methylation 

- FISH to 

chromsome 

3,7,17,9p21 

- DD 23 

- Karyometry 

- Malignant cells 

- Alterations in 

DNA microsatellite 

regions 

- Telomerase 

elongating enzyme 

- Gene regulation 

- Chromosomal 

instability 

- Cancer associated 

antibody 

- Chromosomal 

instability 

11-76% 

72-97% 


70-95% 

68-87% 

73-100% 

>90% 

>95% 

60-70% 

>90% 

33-68% 

Several authors have modeled the affect of introducing a urinary biomarker for 

BCa analysis and surveillance. Most agree that cost savings of around 20% could 

be made by the reduction in cystoscopic surveillance frequency or the avoidance 

of diagnostic cystoscopy [18,19,20]. These projections use markers with 60–70% 

sensitivities and higher specificities. More savings could be made by better 

performing markers. In Egypt, carcinoma of the bladder is the most prevalent


cancer, accounting for as many as 31% of all cancer cases [21]. Currently, it ranks 

first in males representing 16.2% of male cancer [22]. The estimated incidence in 

males in rural areas in Egypt is about 32 per 100.000 [23]. 

The exact etiology of bladder cancer is still unknown. Several risk factors have 

been accused as being involved in its pathogenesis such as cigarette smoking [24], 

synthetic nitrogen fertilizers [25], organophosphate-based pesticides [26], aromatic 

amines [8], pelvic irradiation, cyclophosphamide, chronic cystitis, schistosomiasis 

[24], human papilloma virus [27], genetic predisposition, and some occupations 

[24]. The relative importance of such risk factors in the pathogenesis of the disease 

differs in different populations. 

The consensus of opinion and the amount of scientific evidence available from 

the literature don’t suggest that routine or regular screening for bladder cancer 

is recommended. 

Further work should be done for the identification of simple reliable tests that can 

detect the presence of the disease in high risk patients. 

Intervention Population Recommendation 

Primary Prevention public Avoid known 

carcinogens 

Early Detection public NOT recommended 

Early Detection - high risk population - cytology every 

- history of bladder 2 years 

cancer 

- cytology every 6 

months 

References 

1. Clinical Trials. American Cancer Society. Available at http://www.cancer.org. 

Accessed April 12, 2006. 

2. Feldamn AR, Kessler L, Myers MH and Naughton MD: The prevalence of cancer: 

estimates based on the Connecticut Tumor Registry. N Engl J Med 1986; 315: 1394. 

3. Messing EM: Urothelial tumors of the urinary tract. In: Campbell’s Urology, 

8th ed. Edited by PC Walsh, AB Retik, ED Vaughan Jr, AJ Wein, LR Kavoussi, AC 

Novick et al. Philadelphia: WB Saunders 2002; vol 4, pp 2732–2784. 

4. Badalament RA, Hermansen DK, Kimmel M, Gay H, Herr HW, Fair WR et 

al: The sensitivity of bladder wash flow cytometry, bladder wash cytology, and 

voided cytology in the detection of bladder cancer. Cancer Res 1987; 60: 1423. 

5. Burchardt M, Burchardt T, Shabsigh A, de la Taille A, Benson MC and Sawczuk 

I: Current concepts in biomarker technology for bladder cancers. Clin Chem 

2000; 46:595. 

6. Celis JE, Ostergaard M, Basse B, Celis A, Lauridsen JB, Ratz GP et al: Loss 

of adipocyte-type fatty acid binding protein and other protein biomarkers is 

associated with progression of human bladder transitional cell carcinomas 

Cancer Res 1996; 56:4782. 

7. Quek ML, Sanderson K, Daneshmand S and Stein JP: New molecular markers for 

bladder cancer detection. Curr Opin Urol 2004; 14: 259. 

8. Vlahou A, Schellhammer PF, Mendrinos S, Patel K, Kondylis FI, Gong L et al: 

Development of a novel proteomic approach for the detection of transitional cell 

carcinoma of the bladder in urine. Am J Pathol 2001; 158: 1491. 

9. Wilson JMG, Junger G. Principles and practice of screening for disease. 

Geneva, Switzerland: World Health Organization; 1968. 

10. Messing EM, Young TB, Hunt VB, et al. Comparison of bladder cancer outcome 

in men undergoing hematuria home screening versus those with standard clinical 

presentations.Urology 1995;45:387–96, discussion 96–7. 

11. Britton JP, Dowell AC, Whelan P. Dipstick haematuria and bladder cancer in 

men over 60: results of a community study. BMJ 1989;299:1010–2. 

12. Mayfield MP, Whelan P. Bladder tumours detected on screening: results at 7 

years. Br J Urol 1998;82:825–8. 

13. Messing EM, Young TB, Hunt VB, et al. Home screening for hematuria: results 

of a multiclinic study. J Urol 1992;148:289–92. 

14. Wallace DM. Occupational urothelial cancer. Br J Urol 1988;61:175–82. 

15. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment 

of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 

2001;19:666–75. 

16. Madersbacher S, Hochreiter W, Burkhard F, et al. Radical cystectomy for 

bladder cancer today—a homogeneous series without neoadjuvant therapy. J 

Clin Oncol 2003;21:690–6. 

17. Schrier BP,HollanderMP, van Rhijn BWG, Kiemeney LALM, Witjes JA. 

Prognosis of muscle-invasive bladder cancer: difference between primary and 

progressive tumours and implications for therapy. Eur Urol 2004;45:292–6. 

18. Lachaine J, Valiquette L, Crott R. Economic evaluation of NMP22 in the 

management of bladder cancer. Can J Urol 2000;7:974–80. 

19. Zippe C, Pandrangi L, Agarwal A. NMP22 is a sensitive cost-effective test in 

patients at risk for bladder cancer. J Urol 1999;161:62–5. 

20. Lotan Y, Roehrborn CG. Cost-effectiveness of a modified care protocol 

substituting bladder tumor markers for cystoscopy for the followup of patients 

with transitional cell carcinoma of the bladder: a decision analytical approach. 

J Urol 2002;167:75–9. 

21. Public health impact of schistosomiasis: disease and mortality. WHO Expert 

Committee on the Control of Schistosomiasis. Bull World Health Organ.71(6):657- 

662, 1993. 

22. Khaled HM: Systemic management of bladder cancer in Egypt: revisited; aswell 

as: Expert Opin Investig Drugs. J Egypt Natl Canc Inst., 17(3):127-31, 2005. 

23. Amal SI and El-Sebai I: Epidemiology of bladder cancer and ligand binding. 

In: Cancer bladder, Inc Florida Press, 1:28-32, 1983. 

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http://www.cancer.org/docroot/CRI/content/CRI_2_4_2X_What are the risk factors 

for bladder cancer 44.asp 

25. Mensing TT, Speijers GJ, and Meulenbelt J: Health implications of exposure 

to environmental nitrogenous compounds. Toxicol Rev, 22 (1): 41-51, 2003. 

26. Webster LR, McKenzie GH and Moriarty HT: Organophosphate based 

pesticides and genetic damage implicated in bladder cancer. Cancer Genet. 

Cytogenet, 133(2): 112-117, 2002. 

27. LaRue H, Simoneau M and Fradet Y: Human papilloma virus in transitional 

cell carcinoma of the urinary bladder. Clin Cancer Res, 1:435-438, 1995. 


GASTRIC CANCER 

Omalkhair Abulkhair, MD 1 , Abdul Rahman Jazieh, MD, MPH 1 

(1) King Abdulaziz Medical City for National Guard, Riyadh, KSA 

Corresponding Author: Omalkhair Abulkhair, MD 


King Abdulaziz Medical City for National Guard 



Epidemiology 

Although declined in the United States and the Western World, gastric cancer is 

still high in several countries around the world. Incidence exhibits significant 

geographic variability. The disease is most common in East Asia. High rates have 

been reported in Central and South America, Eastern Europe and parts of Middle 

East. In Japan, gastric cancer remains the most common type of cancer among men. 

The overall incidence of this condition has decreased in the past few decades. 

Nonetheless, gastric cancer remains a major public health issue as the fourth most 

common cancer and the second leading cause of death worldwide. In the first 

quarter of the 20th century, two thirds of gastric cancers were located in the antrum 

and the prepyloric area and only 10% arose in the caria or the esophagogastric 

junction. Since the 1970’s, however, adenocarcinoma of the proximal stomach 

has become increasingly common.1 

The age-adjusted incidence rate in the United States for the years 2000 to 2003 

was 8.1 per 100,000. Incidence among men is twice as high as among women.2 

Mortality rates for gastric cancer have been declining worldwide in recent decades, 

most prominently in the United States.3-4 The death rate from gastric cancer 

for black males was 2.3-fold higher than for whites for the years 1997 to 2001.5 

The annual number of new cases seems to be steady in recent years; in 2008, it is 

estimated 21, 500 Americans will be diagnosed with gastric cancer and 10, 880 

will die of it.6 Worldwide, gastric cancer is the fourth most common cancer.7 

Most cancers in the United States are advanced at diagnosis, which is reflected 

in an overall 5-year survival of 2.3% from 1996 to 2002.2 

On the contrary, in Saudi Arabia, gastric cancer accounts for 3% of all newlydiagnosed 

cancer on the year 200, it ranked 10th among male and 14th among 

female with male to female ratio of 2:1. The overall ASR was 3.1/100,000. The 

median age is 65 years and stage is quite advanced regional in around 50% of area.8 

Highest incidence in Japan, South America and Eastern Europe adjusted worldwide 

is 15.62 per 100,000. Adjusted rate in Latin America is variable in frequent 

before age 40, twice as frequent leading cause of death from cancer worldwide 

in men than women. 

In Costa Rica, the incidence rate for men is 51.5 and 28.7 for women. In USA, 

the incidence has been decreasing and unexplained by the cancer has migrated 

proximally. Gastro-esophageal lesions are more frequent than antral lesions. 

Risk Factors 9-14 

Risk factors can be summarized as follows: 

1. Chronic Athropy 

Chronic atrophic gastritis is thought to be the initial step in the development of most 

gastric cancer, chronic atrophic gastritis has been shown to appear in patients with: 

• Tobacco use 

• H. Pylori infection 

• Diets with high level of nitrites, nitrates, salt and smoked food 

• Previous gastric surgery 

• Pernicious anemia 

• Alcohol 

Smoking increases the risk of gastric cancer by 50% to 60%. It has been estimated 

that smoking tobacco is responsible for 11% of all stomach cancers worldwide. 

Tobacco use decreases the level of caroteroids and vitamin C which act as protective 

agents against this disease. In addition, tobacco use associated with H. pylori 

infection which in turn leads to atrophic gastritis. Smoking cessation returns the 

risk to that of the general population after 20 years. 

H. pylori is associated with 2-6-fold increase in the risk of developing gastric 

cancer. In 1994, the World Health Organization designated H. pylori a group 

of carcinogen. 

Consumption of fruit, vegetables and fiber has shown in the majority of controlled 

studies published, a protective effect against gastric cancer. This is probably due 

to vitamin C or carotenes. 

Nitrites and nitrates found in salted, smoked and dried food lead to atrophic gastritis 

which in turn leads to gastric cancer. 

2. Genetic Factors 

• Small percentage of gastric cancers are hereditary known as hereditary 

diffuse gastric cancer (HDGC) 

• Blood type A 

• Hereditary non-polyposis colorectal cancer 

• E-cadherin gene mutations 

• A first degree relative with gastric cancer 

• Presently, they are not subject to preventive measures except for prophylactic 

gastrectomy in e-cadherin mutations 

Symptoms 

1. Early 

• Indigestion or burning sensation (heart burn) 

• Loss of appetite, especially for meat 

2. Late 

• Abdominal pain or discomfort in the upper abdomen 

• Nausea and vomiting 

• Diarrhea or constipation 

• Bloating of the stomach after meals 

• Weight loss 

• Weakness and fatigue 

• Bleeding (vomiting of blood or having blood in stool which can lead to 

anemia) 



Diagnosis 

The most important is detailed medical history and physical examination and 

then to have laboratory work including full blood count since they might develop 

anemia secondary to blood loss 

• Upper GI endoscoped exam is the diagnostic method of choice. Abnormal 

tissue should be biopsied and sent to a pathologist. 

Histology 

There are several histological types of gastric cancer of which adenocarcinoma is 

by far the, the most frequent. Sarcoma and lymphoma can also incur. Two types 

of adenocarcinoma are recognized: 

1. Intestinal 

Resembles colon cancer, can be polypoid or ulcerated, occurs usually in the distal 

stomach and has prolonged precancerous phase. 

2. Diffuse 

Extends widely with no distinct margins and the glandular structure is rarely 

present. Patient tends to be younger and have a worse prognosis. 

The disease is considered early when confined to the mucosa and sub-mucosa, 

irrespective of lymph node status, otherwise, it is advanced. 

Staging 

• CT chest, abdomen and pelvis 

• Tumor marker CEA, CA 

Treatment 

It depends on the location, size and extent of disease; main therapy – surgery. 

Surgery 

Sub-total or partial gastrectomy or total gastrectomy of the stomach as well as 

some tissue around the stomach with basic goal of removing all cancer and a 

margin of normal tissue. Depending on the extent of invasion and the location 

of the tumor surgery may also include removal of part of the esophagus, spleen 

ovaries or intestine. 

Chemotherapy 

Gastric cancer is not sensitive to chemotherapy and primarily it serves to palliatively 

reduce the size of the tumor and increase survival time. Some of the drugs are 5-FU, 

BCNU, doxorubicin, cisplatin, taxotere-mitomycin. CT can be given before the 

surgery neoadjuvant, post-surgery adjuvant to destroy the remaining cancer cells. 

Radiotherapy 

Gastric cancer has low sensitivity to radiosensitivity. When used, it is often 

combined with surgery and chemotherapy or may be used to relieve pain or 

blockage by shrinking the tumor in case of terminal disease.15-16 

Prevention and Early Detection 

Gastric cancer is a very common disease that carries a high mortality. The 

diagnosis in early phases when better results should be expected is difficult due 

to the unspecificity of early symptoms. 

Recognition of risk factors and application of strategies directed towards their 

elimination are of paramount importance. 

Secondary prevention is the “early” detection of cancer through screening. This 

is done in populations where the disease is a major health problem (e.g. Japan 

and Costa Rica). In Japan, gas-contrast stomach fluorography is done in the mass 

population. Those considered abnormal (about 13%) will undergo for the studies 

endoscopy and biopsy. 

The best primary prevention strategies are: 

1. Smoking avoidance or cessation 

2. Diet rich in fruit, vegetable and fiber 

3. Avoidance of salted, smoked and poorly preserved food 

4. Eradication of H. pylori 

5. Mass screening is a possible strategy in high-risk populations but is not 

uniformly accepted. 

References 

1. Khirurgiia, S. Gastric Cancer: Current state of the problem. Part 1. 

Epidemiology, pathology, classifications and staging. 2007; (4):48-59 PMID: 

18443537 (PubMed) indexed for Mideme 

2. Ries LAG, Harkins D, Krapcho M, et al.: SEER Cancer Statistics Review, 

1975-2003. Bethesda, Md: National Cancer Institute, 2006. Also available online. 

Last accessed October 07, 2008. 

3. Qui D, Tanaka S: International comparisons of cumulative risk of stomach 

cancer, from Cancer Incidence in Five Continents Vol. III. Jpn J Clin Oncol 36 

(2):123-4, 2006. 

4. Stomach. In: Ries LA, Kosary CL, Hankey BF, et al., eds.: SEER Cancer Statistics 

Review 1973-1995. Bethesda, Md: National Cancer Institute, 1998, Section 13. 

5. American Cancer Society.: Cancer Facts and Figures 2005. Atlanta, Ga: 

American Cancer Society, 2008. Also available online. Last accessed October 

1, 2008. 


American Cancer Society, 2008. Also available online. Last accessed October 

1, 2008. 

7. Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2 (9): 

533-3, 2001. 

8. Cancer Incidence, 2004 

9. Stomach. In: World Cancer Research Fund., American Institute for Cancer 

Research.: Food, Nutrition and the Prevention of Cancer: A Global Perspective. 

Washington, DC: The Institute, 1997, pp 148-175. 

10. Buiatti E, Palli D, Decarli A, et al.: A case-control study of gastric cancer and 

diet in Italy : II. Association with nutrients. Int J Cancer 45 (5): 896-901, 1990. 

11. Taylor PR: Prevention of gastric cancer: a miss. J Natl Cancer Inst 99 (2): 

101-3, 2007. 

12. Malila N, Taylor PR, Virtanen MJ, et al.: Effects of alpha-tocopherol and betacarotene 

supplementation on gastric cancer incidence in male smokers (ATBC 

Study, Finland). Cancer Causes Control 13 (7): 617-23, 2002. 

13. Wong BC, Lam SK, Wong WM, et al.: Helicobacter pylori eradication to 

prevent gastric cancer in a high-risk region of China: a randomized controlled 

trial. JAMA 291 (2): 187-94, 2004. 

14. Shimazu, T. Alcohol drinking and gastric cancer risk: an evaluation based 

on a systemic review of epidemiologic evidence among the Japanese population. 

Jpn J Clin Oncol 2008 38(1):8-25;doi:10.1093/jjco/hym152 

15. American Cancer Society. Angiogenesis Institution (National Cancer Institute) 

16. Cancer Treatment Options. May 2009. www.Issels.com 


TESTICULAR CANCER 

Prof Dr. Alaa Kandil 

Alexandria School of Medicine, Egypt 

Corresponding Author: Professor Dr Alaa Kandil 

Department of Clinical Oncology & Nuclear Medicine 

Alexandria School Of Medicine 

601 Elhoreya St, Elgawhara Bld, Zizenia, App 601 

E-mail: alaakandil@ hotmail.com 

It is estimated that 8,090 new cases of testicular cancer will be diagnosed in men, 

and 380 men will die of this disease in the United States in 2008.1 Testicular 

cancer is the most common malignancy in men aged 15 to 35 years. It accounts 

for approximately 1% of all cancers in men. Worldwide, testicular cancer has 

more than doubled in the last 40 years. Incidence varies considerably in different 

geographical areas, being highest in Scandinavia and Switzerland; intermediate 

in the United States, Australia, and the United Kingdom; and lowest in Asia and 

Africa. It also varies according to ethnic groups, with a much higher rate among 

whites than blacks in the American population.2 An annual increase of 3% is 

reported for Caucasian populations.3 Despite the increase in observed incidence, 

there has been a dramatic decrease in mortality as a result of effective treatments. 

Germ cell tumors (GCT) of the testis constitute 94% of testicular tumors and include 

five basic cell types: seminoma, embryonal carcinoma, yolk sac tumor, teratoma, 

and choriocarcinoma. Sixty percent of GCT are seminomas; the remainder are 

nonseminomatous germ cell tumors. Almost half of all germ cell tumors contain 

more than one of the five cell types. 

Three subtypes of pure seminomas have been described: classic, anaplastic, and 

spermatocytic. Classic seminoma accounts for 80% to 85% of all seminomas 

and occurs most commonly in men aged 30 to 50 years. Anaplastic seminoma 

accounts for 5% to 10% of all seminomas and has an age distribution similar to 

that of the typical subtype. A number of features suggest that anaplastic seminoma 

is a more aggressive and potentially more lethal variant of typical seminoma. 

These characteristics include greater mitotic activity, higher rate of local invasion, 

increased rate of metastatic spread, and higher rate of tumor marker (human 

chorionic gonadotropin beta, or beta hCG) production. Spermatocytic seminoma 

accounts for 2% to 12% of all seminomas, and nearly half occur in men older than 

50 years. The cells closely resemble different phases of maturing spermatogonia. 

The metastatic potential of this tumor is extremely low, and the prognosis is 

favorable.4 

Risk Factors 

Unlike most other cancers, testicular cancer is generally found in young men.5 

In white men, testicular cancer is the most common cancer from age 20 years to 

age 34 years, the second most common from age 35 years to age 39 years, and 

the third most common from age 15 years to age 19 years. This type of cancer is 

4.5 times more common among white men than black men,6 with intermediate 

incidence rates for Hispanics, American Indians, and Asians. High-risk groups exist. 

Males with cryptorchidism have 3 to 17 times the average risk. Approximately 

7% to 10% of patients with testicular tumors have a history of cryptorchidism.4, 7 

Orchiopexy may not prevent cancer in these children but allows clinical surveillance 

of patients with a previously impalpable gonad. There is also an increased risk 

in males with gonadal dysgenesis and Klinefelter syndrome.8 Men with a family 

history of testicular cancer may be at a higher risk of this disease.9 A history 

of testicular cancer is associated with a higher risk of a contralateral tumor.4, 7 

Although not consistently found to confer a higher risk, infertility, testicular 

atrophy, twinship, or abnormal semen parameters have been associated with a 

higher risk of testicular cancer, but the evidence is weak.7, 10 

An additional risk factor for the development of testicular cancer is the presence 

of carcinoma in situ (CIS), also called intratubular germ cell neoplasia. Testicular 

CIS appears to develop from fetal gonocytes and is characterized histologically 

by seminiferous tubules containing only Sertoli cells and malignant-appearing 

germ cells. 

If encountered in the contralateral testis, CIS is associated with the development 

of contralateral testicular cancer in 50% of patients at 5 years of follow-up.11 

CIS will be found in approximately 5% of contralateral testes (approximately the 

same rate as cryptorchid testes).12 

The association of testicular microlithiasis with testicular cancer is still of 

questionable clinical significance.13, 14 

Approximately 60% of testicular cancers are localized, 24% are regional, and 14% 

are distant stage at diagnosis. Although there has been no appreciable change in 

the stage distribution at diagnosis, advances in treatment have been associated 

with a 60% decrease in mortality. Testicular cancer is so curable even at advanced 

stages and there are so few cases that it would be virtually impossible to document 

a decrease in mortality associated with screening. 

Treatment options for CIS include observation, radiation therapy, chemotherapy, 

and orchiectomy. Although low-dose radiation therapy can preserve Leydig cell 

function and prevent germ-cell tumor development, a conservative approach of 

observation may also be warranted. Individuals at high risk (e.g., cryptorchidism, 

atrophic testis, and intersex conditions) require close observation. 

Testicular cancer survivors are at an increased risk of solid tumors for at least 

35 years after treatment.15 There is a low cumulative risk of metachronous 

contralateral testicular cancer and a favorable overall survival of patients diagnosed 

with metachronous contralateral testicular cancer.16 

Most testicular cancers are first detected by the patient, either unintentionally 

or by self-examination. Some are discovered by routine physical examination. 

However, no studies have been done to determine the effectiveness of testicular 

self-examination or clinical testicular examination in reducing mortality from 

testicular cancer. The benefit of testicular self-examination is unknown. 

Screening would be very unlikely to decrease mortality substantially because 

therapy is so effective, even for advanced stages of disease. However, early 

detection may have a practical impact on therapy. There is an increase in both 

the number of courses of chemotherapy and the extent of surgery required for 

treatment of advanced disease that results in higher morbidity. Patients diagnosed 

with localized disease require less treatment and have lower morbidity.17 

References 


American Cancer Society, 2008. 

2. Huyghe E, Matsuda T, Thonneau P: Increasing incidence of testicular cancer 



worldwide: a review. J Urol 170 (1): 5-11, 2003. http://www.ncbi.nlm.nih.gov/entrez/ 

query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12796635&dopt=Abstract 

3. Horwich A, Shipley J, Huddart R: Testicular germ-cell cancer. Lancet 367 

(9512): 754-65, 2006 

4. Richie JP, Steele GS: Neoplasms of the testis. In: Walsh PC, Retik AB, Vaughan 

ED, et al., eds.: Campbell's Urology. 8th ed. Philadelphia: Saunders, 2002, pp 

2876-2910. 

5. Ries LA, Kosary CL, Hankey BF, et al., eds.: SEER Cancer Statistics Review 

1973-1995. Bethesda, Md: National Cancer Institute, 1998. 

6. Moul JW, Schanne FJ, Thompson IM, et al.: Testicular cancer in blacks. 

A multicenter experience. Cancer 73 (2): 388-93, 1994. http://www. 

ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ 

uids=8293405&dopt=Abstract 

7. Dieckmann KP, Pichlmeier U: Clinical epidemiology of testicular germ cell 

tumors. World J Urol 22 (1): 2-14, 2004 

8. Henderson BE, Benton B, Jing J, et al.: Risk factors for cancer of the testis in 

young men. Int J Cancer 23 (5): 598-602, 1979. http://www.ncbi.nlm.nih.gov/ 

entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=37169&dopt=Abstract 

9. Dieckmann KP, Pichlmeier U: The prevalence of familial testicular cancer: 

an analysis of two patient populations and a review of the literature. Cancer 80 

(10): 1954-60, 1997 

10. Jacobsen R, Bostofte E, Engholm G, et al.: Risk of testicular cancer in men 

with abnormal semen characteristics: cohort study. BMJ 321 (7264): 789-92, 2000 

11. Jørgensen N, Müller J, Giwercman A, et al.: Clinical and biological significance 

of carcinoma in situ of the testis. Cancer Surv 9 (2): 287-302, 1990 

12. Dieckmann KP, Loy V: Prevalence of contralateral testicular intraepithelial 

neoplasia in patients with testicular germ cell neoplasms. J Clin Oncol 14 (12): 

3126-32, 1996 

13. Holm M, Hoei-Hansen CE, Rajpert-De Meyts E, et al.: Increased risk of 

carcinoma in situ in patients with testicular germ cell cancer with ultrasonic 

microlithiasis in the contralateral testicle. J Urol 170 (4 Pt 1): 1163-7, 2003 

14. Rowland RG: Editorial: testicular malignancies--high chance of curecontinuing 

opportunities to refine treatment. J Urol 170 (4 Pt 1): 1168, 2003 

15. Travis LB, Fosså SD, Schonfeld SJ, et al.: Second cancers among 40,576 

testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 97 

(18): 1354-65, 2005 

16. Fosså SD, Chen J, Schonfeld SJ, et al.: Risk of contralateral testicular cancer: 

a population-based study of 29,515 U.S. men. J Natl Cancer Inst 97 (14): 1056- 

66, 2005 

17. Sagalowsky AI: Expectant management of stage A nonseminomatous testicular 

tumors. In: Ratiff TL, Catalona WJ, eds.: Genitourinary Cancer. Boston: Martinus 

Nijhoff, 1987, pp 225-237. 

THYROID CANCER EPIDEMIOLOGY AND PREVENTION 

Saad Al Shehri, MD, FRCSC, FACS 


Corresponding Author: Saad Al Shehri, MD, FRCSC, FACS 

Department of Surgery, P.O. Box 22490, Riyadh 11426 

Kingdom of Saudi Arabia 

E-mail: shehris@ngha.med.sa 

Introduction 

The thyroid gland is made up of two lateral lobes which extend from the sides of 

the thyroid cartilage to the sixth tracheal ring. These are joined together by the 

isthmus which overlies the second to fourth tracheal rings. 

The thyroid gland is the largest organ specialized in endocrine function in the 

human body. 

Cells of Origin: 

Thyroid gland contains two embryologically and functionally different cell types: 

• The neuroendocrine Calcitonin producing C – cell and 

• Endodermally derived follicular cell that produces T4 and Thyroglobulin 

Thyroid cancers are derived from these two embryonic cell lines. 

Classification of Thyroid Cancer: 

1. Papillary Carcinoma 

• 80% of thyroid cancer 

• Peak age: 3rd, 4th decades 

• More in women (3 folds) 

• More in white 

2. Follicular Carcinoma 

• 10% of thyroid cancer 

• Peak age: 4th and 5th decades 

• More frequent in women 

• Uncommon in black 

3. Medullary Thyroid Carcinma (MTC) 

• 5 – 7% of thyroid cancer 

• Sporadic type 80% 

• Familial type 20%, point of mutation in the RET proto – oncogene. In kindred 

with MTC can identify affected persons can be identified before clinical or 

chemical changes can be detected (1,2) 

4. Anaplastic Thyroid Carcinoma 

• Arises from less differentiated thyroid cell 

• Caused by external radiation (3) 

• Occurs with greater frequency in areas of low iodine diet and endemic 

goiter area (4) 

• More in elderly, 76% more in women (ratio 2:1) 

• 1/3 of specimen have areas of well differentiated, rare in children 

• Treatment ranges from debulking and post operatively radiation to systemic 

chemotherapy 

• Median survival is 6 months 


5. Thyroid Lymphoma 

• It occurs with greater frequency than anaplastic carcinoma 

• Incidence has increased in recent years 

• Hashimoto’s disease increased patient’s risk of thyroid lymphoma about 

70 fold (5) 

• Mean: age from 60 to 65 

• Female to Male: 8:1 (6) 

• Prognosis depends on stage if confined to thyroid, 5 year survival rate is 85% 

if extending into surroundings neck structure (35%) and for disseminated 

disease rate (5%) (7) 

• Treatment is radiotherapy alone and surgery and radiotherapy together are 

highly effective 

6. Secondary Thyroid Tumor 

• Microscopic metastasis to thyroid gland found in autopsy specimens from 

patients with malignant melanoma, lung and breast carcinoma 

• Usually undetectable clinically 

• Does not alter the thyroid function 

Epidemiology 

Thyroid cancer is a relatively uncommon clinical problem. In USA, account for 

less than 1.5 of all cancer cases. This appears to be steadily increasing in incidence. 

In the 1970’s, 8000 new cases / year. In 2002, there were 20, 700 cases /year but 

the death rate remained the same with fewer than 1300 case / year. 

Thyroid cancer constitutes 92% of endocrine cancers (8). The incidence of thyroid 

cancer is high in males with thyroid nodules and among patients younger than 30 

years old or older than 60 years of age (9) 

The prevalence of occult thyroid carcinoma in autopsy specimen is about 10%. 

(10,11) 

In Saudi Arabia(12): 

There were 415 cases of thyroid cancer accounting for 6% of all newly diagnosed 

cases in year 2004. This cancer ranked second among female population and 14th 

among male population. It affected 87 (21%) males and 328 (79%) females with 

a male to female ratio of 100:266. 

Risk Factors 

1. Benign Thyroid Disease 

Because thyroid cancer occurs more often in solitary nodules than in multinodular 

goiters (MNG) the two are often managed differently; however, this may lead to 

a serious diagnostic error. Up to 50% of thyroid glands, with palpable solitary 

nodules have multiple lesions by ultrasound or at surgery. (13,14) 

A dominant hypofunctional nodule in MNG or a diffuse goiter with large palpable 

cervical lymph nodes should be evaluated for carcinoma. Hashimato’s thyroiditis 

can transform to lymphoma in 20 – 30% of the cases. 

2. Radiation Exposure 

This is an important risk factor for thyroid carcinoma and other head and neck 

neoplasms (15,16,17). Medical workers exposed to radiation have a significantly 

high prevalence of thyroid cancer than controls (18). 

The risk of developing carcinoma is greatest after radiation exposure in childhood. 

Likewise, persons exposed to radiation from atomic weapons and nuclear fallout 

accidents have a highly incidence of thyroid cancer. 

The latest period for developing abnormality after radiation exposure is commonly 

between 10 – 20 years of age, but it can happen during childhood. 

3. Diet 

Epidemiologic studies relating diet, iodine consumption and iodine deficiency to 

thyroid cancer have not clearly demonstrated a universal link. 

4. Genetic Factors 

The evidence is growing that genetic factors may play a role in a small percentage of 

papillary and follicular thyroid carcinomas. Good example of that the well known 

association between Gardner’s Syndrome (familial polyposis) and Cawden’s 

disease (familial goiter and skin hematomas). (19,20) 

5. Hereditary Medullary Thyroid Carcinoma 

• A manifestation of multiple endocrine neoplasia: 

• MEN 2A: Medullary thyroid cancer, pheochromocytoma, 

parathyroid neoplasia 

• MEN 2B: Medullary thyroid cancer, Marfanoid features 

• Familial medullary thyroid carcinoma with no other endocrine diseases. 


Patients with thyroid cancer may have one or more of the following signs and 

symptoms: 

1. Firm hard, painless lump in the front of the neck 

2. Swelling in the neck (goiter) 

3. Swallowing difficulty (pressure) 

4. Hoarseness or change in voice (pressure or invasion of recurrant laryngeal nerve) 

5. Coughing with hemoptysis (invasion of trachea) 

6. Breathing difficulty (pressure) 

7. Unexplained bone fractures (follicular) 

8. Severe flushing or diarrhea (medullary) 

Screening 

Genetic testing can identify members of an affected kindred at birth. (21) It is 

indicated if a patient with familial MTC has a mutation in the RET proto – oncogene 

and is then indicated in all first – degree relatives. Those with a positive test, 

including children, should undergo thyroidectomy. Serum calcitonine measurement 

should be done during follow up visits. Patients with MEN 2A and MEN 2B 

should have urinary catechalamines and metanephrines and serum calcium level 

during follow up. 

Although the molecular abnormalities in papillary and follicular thyroid carcinoma 

are undoubtedly important, no direct clinical application at this time, but it might 

in the future. 

Prognosis and Outcome 

For Well Differentiated Thyroid Cancer 

Patient under 45 years old have better prognosis, women do better than men. There 

is linear relationship between tumor size and prognosis, also histological type and 

extent or local invasion of tumor are significant prognostic factors. 



For Medullary Thyroid Cancer 

Early therapy has improved survival with MTC in patients with MEN 2A, and 

has decreased the frequency of distant metastasis. The prognosis of patients 

with the MEN 2B is substantially worse than patients with MEN 2A but it is also 

improved by early diagnosis and therapy. Outcome is most favorable in patients 

with familial MTC without associated endocrine tumors. 

Anaplastic Tumors 

Dismal prognosis with a median survival of 6 – 12 months. 

Prevention 

Primary: Eliminate the Risk Factors 

Due to the fact that not all the risk factors for thyroid malignancy are known, it 

is difficult to conduct complete primary prevention. 

Factors like exposure to radiation can be controlled by minimizing x – ray exposure 

to children and thyroid gland by using shields. 

There is a scientific and political responsibility to control nuclear plants and avoid 

accidents, and early public notification if occurred. 

Secondary: Early Detection and Treatment 

In case of familial thyroid carcinoma: 

• To conduct genetic screening 

• And regular check up by physical exam and ultrasound testing. If any lesion 

is noted in thyroid gland, obtain biopsy. 

Treatment includes: 

• Surgical resection 

• Clearance of lymph nodes, if any 

• + Radioactive Iodine 

• + External beam radiation 

• Also thyroids hormone supplements post operatively 

Tertiary: Prevent Recurrence and Decrease Mortality 

For Well Differentiated Thyroid Carcinoma: Testing for metastasis using thyroid 

scan and also monitoring the serum thyro globuline level. 

For Medullary Thyroid Carcinoma: The monitoring of serum calcitonin gives 

very good indicator of treatment, efficacy and outcome. 

In advanced thyroid cancer, palliative measures including pain control, protect 

airway (Tracheostomy), maintains enteral feeding (Gastrostomy). 

Recommendations of Prevention and Early Detection of Thyroid Cancer 

Primary Preventions: 

• Avoid exposure to radiation neither accidental nor excessive medical 

exposure. 

• Although it is not clear risk factor, but it is advisable to avoid low iodine 

in diet 


• No clinical and cost effective method with proven benefit for screening the 

population for thyroid cancer in general. 

Early Detection in Special Population: 

• Calcitonin level in patient with MEN Syndrome for medullary carcinoma 

• Close observation for certain benign condition e.g. Hashimoto’s disease, 

Gardner’s Syndrome and Cawden’s Disease since there is association with 

thyroid cancer. 

The serum calcitonin and serum thyroglobulin can be used as a marker for early 

detection of recurrence of some of the thyroid cancers. 

References 

1. Sondik EJ and other: 1986 Annual Cancer Statistics Review. Belhesda 1986. 

Department of Health and Human Services. Public Health Service. National 

Cancer Institute. 

2. Cornea P, Chen VW: Endocrine Gland Cancer, Cancer 75: 338, 1995. 

3. Belfiore A and others: Cancer Risk in Patients with Cold Thyroid Nodules: 

Relevance of Iodine Intake, Sex, Age and Multinodulanity, A.M.J. Med 93: 363, 

1992. 

4. De Vathaire F and others: Epidemiological Evidence for a Common Mechanism 

for Neuroblastoma and Differentiated Thyroid Tumor, BrJ. Cancer 65: 425, 1992. 

5. Mazzferri El, de los Santos ET, Rofagha – Keyhanis: Solitary Thyroid Nodules: 

Diagnosis and Management, Med Chin North Am 72: 1177, 1988. 

6. Al – Saleh Ms., Al – Kattan KM: Incidence of Carcinoma in multinodular 

Goiter in Saudi Arabia, J.R. Coll Surg. Edinb 39: 106, 1994. 

7. Roher HD: Thyroid Cancer: is the Radical Surgical Principle Changing? 

Longerbecks Arch Chir 370:1; 1987. 

8. Schneider AB and others: Radiation Induced Tumors of the Head and Neck 

Following Childhood Immediation: Prospective Studies. Medicine (Baltimore) 

64: 1, 1985. 

9. Schneider AB and others: Radiation – Induced Thyroid Carcinoma: Clinical 

Course and Results of Therapy in 296 Patients. Ann Intern Med 105: 405, 1986. 

10. Valdiserri RO, Borochovitz D: Histologic Changes in Previously Innadiated 

Thyroid Gland:. Arch Path Lab Med 104: 150, 1980 

11. Antonelli A and others: Risk of Thyroid Nodules in Subjects Occupationally 

Exposed to Radiation: A Cross – Sectional Study, Occup Envison Med 52: 500, 

1995. 

12. Donis – Keller H and others: Mutations in the RET Proto – Oncogene are 

Associated with Menza and FMTC, Hum Genet 2: 852, 1993. 

13. Mulligan LM and Others: Germline Mutations of the RET Proto Oncogene 

in Multiple Endocrine Neoplasia Type 2A, Nature 363: 458, 1993. 

14. Plial RO, Bussey HJR, Thomson JPS: Adenomatous Polyposis An Association 

with Carcinoma of the Thyroid Br. J. Surg 74: 377, 1987. 

15. Sogol PB, Sugawara M, Gordon HE, et al: Cowden’s Disease: Familial Goiter 

and Skin Hamartomas. A Report of Three Cases. West J Med 139: 324, 1983. 

16. Saudi Cancer Registry, 2004 

17. Komorowski RA, Hanson GA, Garancis JC: Anaplastic thyroid carcinoma 

following low – dose irradiation, Am J Clin Pathol 70: 303, 1978. 

18. Hedinger C: Geographic pathology of thyroid diseases. Pathol Res Pract 

171:285. 1981. 

19. Holm LE, Blomgren H. Lowenhagen T: Cancer risks in patients with chronic 

lymphocytic thyroiditis. N Engl J Med 312: 601. 1985. 

20. Mazzaferri EL, Oertel YC: Primary malignant lymphoma and related 

lymphoproliferative disorders. In Mazzaferri EL, Samaan N, editors: 

21. Hamburger JI, Miller JM, Kini SR: Lymphoma of the thyroid, Ann Intern 

Med 99: 685, 1983. 


COLORECTAL CANCER: 

PREVENTION AND EARLY DETECTION 

Jazieh, A., Abulkhair, O., Olayan, A, Mahmood, R. 

King Abdulaziz Medical City, Riyadh, KSA 


Chairman, Department of Oncology, King Abdulaziz Medical City 



Abstract 

Colorectal cancer (CRC) is the third most common malignancy and second leading 

cause of cancer death irrespective of gender. 

A number of genetic, environmental and life style risk factors are involved 

in the pathogenesis of CRC. In addition, several studies have established a 

number of factors with a protective role against development of colorectal cancer. 

Identification of these factors and subsequent modification can help us in preventing 

this potentially lethal disease. 

Screening for CRC can help us in two ways. First, it can detect sub-clinical 

abnormalities which may have a potential for malignant transformation and prompt 

us for early action and thus can prevent CRC. Secondly, it helps in the detection 

of CRC at an early stage when clinical symptoms may not be that evident for an 

affected individual to seek medical advice. However, treatment at this early stage 

is most effective and curative in most cases. 

The following manuscript describes the summary of protective and risk factors of 

CRC and screening modalities which can help us in prevention and early detection 

of colorectal cancer. 

Introduction 

Colorectal cancer (CRC) is the third most common malignancy and potentially 

a lethal disease if not treated.¹ It is the second leading cause of cancer death in 

the US.² The importance of prevention and early detection of certain cancers 

cannot be over-emphasized due to the fact that many malignancies are potentially 

preventable. 3, 4 

Epidemiology 

The number of diagnosed cases of CRC annually in the U.S. is close to 150,000 

and approximately one third of them die from the diseas.2 

CRC is seen mostly after the age of 40, with the risk increasing with each decade. 

5,6 90 percent of cases are seen in age more than 50 years. It is seen most common 

in North America, Australia and Europe as compared to Africa and Asia.7 

The overall 5-year survival rate for colorectal cancer is approximately 66 percent. 

Although there have been advances in the surgical and adjuvant treatment of CRC, 

the prognosis remains poor for patients who present at an advanced stage. 8, 9 

Pathogenesis of Colorectal Cancer 

Adenomatous polyps are thought to be a precursor of CRC. 10 It takes about 10 

years in the progression of a polyp from a small size to a large one, then dysplasia 

and ultimately neoplastic appearance. 11, 12 

This has led to the development of screening tools for early detection and removal 

of adenomatous polyps with evidence of lower incidence of CRC in such patients.13 

Risk Factors for Colorectal Cancer 

The various risk factors increasing the likelihood of development of colorectal 

cancer are listed in Table 1. 

A. Familial Adenomatous Polyposis (FAP) 

FAP is caused by a mutation in adenomatous polyposis coli (APC) gene and 

accounts for less than 1% of cases of CRC.14, 15 It is characterized by appearance 

of numerous colonic polyps appearing in childhood and may transform into 

malignancy by age 45 in 90% untreated cases. 

B. Hereditary nonpolyposis colorectal cancer (HNPCC) 

Also know as Lynch syndrome.16 It accounts for 1-5% of CRC. It is an autosomal 

dominant syndrome; caused by mutations in mismatch repair genes; with early age 

of onset and involvement of proximal colon. It may also involved extra colonic 

sites including endometrial carcinoma, stomach, small bowel, Hepatobiliary system. 

C. Personal history of sporadic cancers or adenomatous polyps 

1.5 to 3% patients with a history of resected colorectal cancer can develop CRC 

in first 5 years. Presence of adenomas also poses a threat for CRC especially if 

multiple polyps are present.17 

D. Family history of sporadic cancers or adenomatous polyps 

A first degree relative with CRC increases the risk by 1.7 fold with further increase 

if two first degree relatives are involved. The risk is also present if there is a family 

history of a polyp larger than 1 cm in size.18 

E. Inflammatory bowel disease 

Inflammatory bowel disease (ulcerative colitis and Crohn’s disease) also increase 

the risk of CRC by 5 to 15-fold. The risk is increased at 8 to 10 years after the 

onset of symptoms. 19-21 

F. Other risk factors 

Various other risk factors have been identified as risk factors for development of 

colorectal cancer. These include: 

• Diabetes mellitus and insulin resistance22-27 

• Cholecystectomy28-32 

• Alcohol33-39 

• Obesity40-43 

• Coronary heart disease44 

• Cigarette smoking45, 46 

• Acromegaly47, 48 

• Red meat and caffeine49-55 

• History of radiation therapy for prostate cancer56 

• HIV57, 58 

• Prior treatment for Hodgkin’s Lymphoma59 

Protective Factors for Colorectal Cancer 

A number of protective factors have been identified and have been summarized 

in Table 2. 



A. Diet 

The dietary factors with a protective role against colorectal cancer include: 

• High Fiber diet, diet high in fruits and vegetables60-63 

• Folic acid97, 98 

• VitaminB6 64 

• Calcium65-72 

• Magnesium73 

B. Non Steroidal Anti Inflammatory Drugs (NSAIDs) 

There is evidence on bases of observational studies that aspirin and NSAIDs 

(Celecoxib) may have a protective role against development of colorectal cancer, 

however, there is also documented harm of use of aspirin and NSAIDs due to 

their side effects. 

C. Physical Activity 

Regular physical activity has been identified as a protective factor. Several studies 

support this finding.76-78 

D. Chemoprevention 

D, L, alpha-difluoromethylornithine (DFMO) and sulindac (a NSAID) used in a 

group of patients with history of colonic adenoma showed reduction in development 

of recurrent adenomas in a clinical trial.79 However, further investigation is 

required to confirm the benefits of this in the colon cancer prevention. 

E. Other Protective Factors/Agents 

Other protective factors have been reported which includes: 

• Hormone replacement therapy8085 (Not routinely recommended for 

prevention of colorectal cancer in women due to long-term, risks)86 

• Statins87-89 

• Antioxidants90 

• Omega 3 Fatty Acids (Fish Oil)91 

• Garlic92, 93 

F. Screening for Colorectal Cancer 

Screening for colorectal cancer is summarized in Table 3. (95-101) 

Screening is divided into 3 population groups: 

1. Population at Average Risk 

• Age more than or equal to 50 years 

• No history of adenoma 

• No history of inflammatory bowel disease 

• Negative family history 

2. Population at Increased Risk 

• Personal history of adenoma 

• Personal history of colorectal cancer 

• Personal history of inflammatory bowel disease 

• Positive family history of first degree relative with colorectal cancer or 

adenoma. 

3. Population with Hereditary Risk 

• Hereditary non-polyposis colorectal cancer syndrome (HNPCC) 

• Familial Adenomatous Polyposis (FAP) 

G. Tests Used for Screening for Colorectal Cancer 

Screening with Stool-Based Tests 

• Guaiac-based fecal occult blood test. (Gfobt) 

• Immunochemical tests for fecal blood 

• Fecal DNA tests 

Colon Imaging and Direct Visualization 

• Double contrast barium enema. (DCBE) 

• Sigmoidoscopy 

• Colonoscopy 

• Computed tomographic colonography. (CTC) 

H. Recommendations for Screening for Average Risk Population 

• Offer screening beginning at age 50 years for average risk patients. 

Colonoscopic detection of colorectal cancer is uncommon in asymptomatic 

people under the age of 50 [94]. 

• Discontinue screening when the individual’s estimated life expectancy is 

less than 10 years. 

• No single test is of unequivocal superiority. Incorporating patient personal 

preferences may increase the likelihood that screening will occur. 

• Screening should be supported by a program that assures proper follow-up 

of abnormal findings, and ongoing testing at identified intervals. 

I. Recommendations for Screening for High Risk Population 

• People with a first-degree relative (parent, sibling, or child) with colon 

cancer or adenomatous polyp diagnosed at age less than 60 years, or two 

first-degree relatives diagnosed at any age should be advised to have screening 

colonoscopy starting at age 40 years, or 10 years younger than the earliest 

diagnosis in their family, whichever comes first, and repeated every 5 years. 

• People with a first-degree relative with colorectal cancer or adenoma 

diagnosed at age more than 60 years should be advised to have screening 

as average-risk persons but beginning at age 40 years. 

• People with two or more second-degree relatives (grandparent, aunt, uncle) 

with colorectal cancer should similarly be advised to begin screening at 

age 40 years. 

• People with one second-degree relative or third-degree relative (greatgrandparent 

or cousin) with colorectal cancer should be advised to be 

screened as average risk persons. 

• Individual at high risk with familial syndromes (NHPCC, FAP) should be 

screened for CRC with colonoscopy at frequent specified intervals. 


Table 1: Risk Factors for Colorectal Cancer 

Risk Factors Ralative Risk Age Comments 

Familial adenomatous polyposis 

(FAP) 

Hereditary nonpolyposis colorectal 

cancer (HNPCC) 

Personal history of colorectal cancer 

or adenomatous polyps 

Family history of colorectal cancer or 

adenomatous polyps 

- 90% absolute risk of development 

of colorectal cancer by age 45 in 

mutation carriers 

- 80% absolute risk of development 

of colorectal cancer by age 75 in 

mutation carriers 

3.5 to 6.5 with adenomatous polyps 

>1cm 

1.7 fold increased risk with single 

affected first degree relative with 

CRC 

Inflammatory bowel disease 5 to 15-fold increased risk with 

pancolitis. Three-fold relative risk 

with left-sided disease 

Diabetes mellitus CRC 30% higher in diabetics. 

Relative Risk 1.30 

- Appearing during childhood 

- Symptoms at 16 years 

- Colorectal cancer by age 45 (in 90% 

of untreated individuals) 

- Early age of onset (mean age 48 

years, some present in 20s) 

- Increased risk of index case 

diagnosed at age 1cm 

has same significance as positive 

family history of CRC 

- Increased risk of ulcerative colitis 

and primary sclerosing cholangistis 

are together 

Cholecystectomy Standardized incidence ratio 1.16 - Data shows slightly increased risk of 

right-sided colon cancer 

- Conflicting data also reported 

Alcohol Consumption Adjusted relative risk 1.41 - Seen with alcohol consumption > 

45 g/day 

Obesity 1.5-fold increased risk - Increased likelihood of death from 

CRC 

Cigarette Smoking Relative risk of 1.18 for CRC 

development. 

Relative risk of 1.25 for death from 

CRC 

- Stronger association with rectal 

cancer 

- Stronger risk for development of 

polyps 

Coronary heart disease - Increased risk of advanced 

adenomas 

Acromegaly - Increase prevalence of polyps in 

males only 

Red meat and caffeine - Increased risk of CRC with longterm 

red meat/ processed meat 

consumption 

- Data inconsistent and controversial 



Table 2: Protective Factors for Colorectal Cancer 

Protective Factors Relative Risk/Protective Effect Comments 

Dietary Factors 

Diet high in fruits and vegetables 

Diet low in red meat/cholesterol Relative risk of 3.26 with high cholesterol 

Fiber Up to 40% reduction in CRC risk as claimed in one 

study (on doubling fiber intake in population with 

low fiber intake) 

0.5 - Protective effect seen in may studies 

- Discordant data also published 

- Many conflicting studies 

- Protective role remains controversial 

Folic Acid 0.25 - Protective effect seen after 15 years use 

- Studies suggest protective effect seen with dietary 

folic acid 

Vitamin B6 (Pyridoxine) 0.42 - Total vitamin B6 intake inversely related with 

colon cancer risk 

Calcium 0.65 (Distal Colon Cancers) - Higher calcium intake > 1250mg/d protective 

Magnesium 0.59 - Up to 40% risk reduction observed 

Omega 3 fatty acids (mainly fish oil) 0.88 - Protective effect with high consumption of fish 

Garlic - Reduced risk of colonic adenomas 

PHYSICAL ACTIVITY 0.60 (light occupational activity) 

0.45 (moderate/heavy activity) 

0.33 (most active men) 

ASPIRIN and NSAIDS - No adequate studies available - Observational 

and intervention trial evidence supports protective 

effect 

CHEMOPREVENTION (Combination of D,L 

alpha – diflouromethylornithine DFMO and 

sulindac (NSAID) 

70% reduction in recurrent adenomas 

90% reduction in advanced adenomas 

95% reduction in multiple adenomas 

HORMONE REPLACEMENT THERAPY Risk reduction by 40% with combined estrogen 

plus progestin. 

- Protective effect in patients with history of 

colonic adenoma 

- Controversial data about protective effect. 

- Not routinely recommended due to associated 

risks 

STATINS - Conflicting data about protective effect 

- Use of statins for 5 years proved protective 

Negative family 

history 

Screening Only 

Table 3: Screening for Colorectal Cancer 

Population at Risk Intervention Procedure Frequency Start Age (Yrs) Stop Age (Yrs) Further Action 

AVERAGE RISK 

Colonoscopy Every 10 yrs 50 70 Polypectomy if 

polyps found 

Age more than or 

equal to 50 years 

No history of 

adenoma 

Screening and 

Prevention 

Computed 

Tomographic 

Colonography 

Flexible 

Sigmoidoscopy 

Every 5 yrs 

Every 5 yrs 

50 

50 

70 

70 

Colonoscopy if any 

positive findings 

No history of 

Double Contrast Every 5 yrs 50 70 

inflammatory bowel 

Barium Enema 

disease 

Guaiac Based Fecal 

Occult Blood Testing 

Annually 

50 

70 

Fecal 

Immunohistochemical Annually 

Based Testing for 

Blood 

Stool DNA Testing Uncertain 

Frequency 


50 

70 

50 70 

Flexible 

sigmoidoscopy or 

CT Colonography if 

positive

Population at Risk Intervention Procedure Frequency Start Age (Yrs) Stop Age (Yrs) Further Action 

INCREASED RISK 

Within 5 years of 

detection of polyp 

70 Polypectomy 

Personal history of 

adenoma, colorectal 

or inflammatory 

bowel disease IBD 

(Crohn’s disease or 

Ulcerative colitis) 

Positive family 

history of first 

degree relative with 

colorectal cancer of 

adenoma 

HEREDITARY 

RISK 

Non-Polyposis 

Colorectal Cancer 

(HNPCC)/Lynch 

Syndrome 

Screening Colonoscopy 

Within 1 yr of 

personal history of 

CRC 

Every 1 – 2 years 

(for symptomatic 

IBD) 

Screening Colonoscopy Every 5 years 

When detected post 

operative 

70 Repeat every 3 yrs if 

normal 

8-10 years after IBD 

symptoms Biopsies 

At age 40 yrs or 10 

yrs prior to earliest 

cancer in family 

Screening Colonoscopy Every 1-2 years 20-25 or 10 years 

prior 

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PROSTATE CANCER SCREENING 

Dr. Alaa Kandil 

Alexandria School of Medicine, Alexandria, Egypt 

Corresponding Author: Dr. Alaa Kandil 

Professor of Clinical Oncology, Alexandria School of Medicine 

Alexandria, Egypt 

E-mail: alaakandil@hotmail.com 

Abstract 

Background: Prostate cancer is a very common malignancy affecting males 

worldwide. There is a need to understand its risk factors, early detection and 

prevention approach to this disease. 

Methods: Prostate cancer risk factors, early detection were reviewed from the 

literature and the available guidelines for screening were reviewed and summarized. 

Results: Prostate cancer early detection can be done by performing digital rectal 

examination and obtaining prostate specific antigen (PSA). Although generally 

the screening is done after age 50, in some higher risk group, it should be done 

at younger age. However, this has to be done after discussion with the patients 

each individual situation. General public screening is controversial and there is 

no prove of impact on survival. 

Conclusion: Screening for prostate cancer should be individualized and patients 

should be counseled about it prior to performing the test. 

Prostate cancer is the most common cancer diagnosed in North American men, 

excluding skin cancers. It is estimated that in 2008, approximately 186,320 new 

cases and 28,660 prostate cancer-related deaths will occur in the United States. 

Prostate cancer is now the second leading cause of cancer death in men, exceeded 

only by lung cancer. It accounts for 25% of all male cancers and 10% of male 

cancer-related deaths.(1) 

Regional differences have been observed in prostate cancer incidence and mortality 

rates and in rates of radical prostatectomy. The increased incidence until 1989 

was most likely the result of increased tumor detection due to increasing rates 

of transurethral prostatectomy(2, 3) Subsequent increases were most likely the 

result of widespread use of PSA testing for early detection and screening.(4, 5) 

Risk Factors 

Prostate cancer is uncommonly seen in men younger than 50 years; the incidence 

rises rapidly with each decade thereafter. The age-adjusted incidence is higher 

in African American males (258.3 per 100,000) than in white males (163.4 per 

100,000)(6) 

African American males have a higher mortality from prostate cancer, even after 

attempts to adjust for access-to-care factors.(7) 

Men with a family history of prostate cancer are at an increased risk of the disease 

compared with men without this history.(8, 9) 

Other potential risk factors besides age, race, and family history of prostate cancer 

include alcohol consumption, vitamin or mineral interactions, and other dietary 

habits.(10 – 14) 

There is an association between primary tumor volume and local extent of disease, 

progression, and survival.(15) 

A review of a large number of prostate cancers in radical prostatectomy, cystectomy, 

and autopsy specimens showed that capsular penetration, seminal vesicle invasion, 

and lymph node metastases were usually found only with tumors larger than 

1.4 cc.(16) Furthermore, the semiquantitative histopathologic grading scheme 

proposed by Gleason is reasonably reproducible among pathologists and correlates 

with the incidence of nodal metastases and with patient survival in a number of 

reported studies.(17) 

Cancer statistics from the American Cancer Society and the National Cancer 

Institute indicated in 2004 that the proportion of disease diagnosed at a locoregional 

stage and at a distant stage is 91% and 5% for whites, compared with 89% and 

7% for African Americans, respectively.(18) Stage distribution of prostate cancer 

is affected substantially by the intensity of early detection efforts. 

With the proliferation of PSA for early detection, reviews of large numbers of 

asymptomatic men with prostate cancer found that most have organ-confined 

disease. One study found that 63% of cancers detected in men undergoing their 

first screening PSA were pathologically organ-confined cancers; the percentage 

increased to 71% if cancer was detected on a subsequent examination. (19) 

Screening 

Before the 1990s, the digital rectal examination (DRE) was the test traditionally 

used for prostate cancer screening. Two other procedures are also available: 

transrectal ultrasound (TRUS) imaging and serum prostate-specific antigen (PSA) 

concentrations.(20) 

Digital Rectal Exam (DRE) 

Although DRE has been used for many years, careful evaluation of this modality 

has yet to take place. Several observational studies have examined process measures 

such as sensitivity and case-survival data, but without appropriate controls and 

with no adjustment for lead-time and length biases.(21, 22) 

Since PSA assays became widely available in the late 1980s, DRE alone is rarely 

discussed as a screening modality. A number of studies have found that DRE has 

a poor predictive value for prostate cancer if PSA is at very low levels. 

In the European Study on Screening for Prostate Cancer, it was found that if DRE 

is used only for a PSA higher than 1.5 ng/mL (thus, no DRE is performed with 

PSA < 1.5 ng/mL), 29% of all biopsies would be eliminated while maintaining 

a 95% prostate cancer detection sensitivity. By applying DRE only for patients 

with a PSA higher than 2.0 ng/m, the biopsy rate would decrease by 36% while 

sensitivity would drop to only 92%.(23) 

A previous report from this same institution found DRE to have poor performance 

characteristics. Among 10,523 men randomly assigned to screening, it was reported 

that the overall prostate cancer detection rate using PSA, DRE, and TRUS was 

4.5% compared with only 2.5% if DRE alone had been used. Among men with a 

PSA lower than 3.0 ng/mL, the PPV of DRE was only 4% to 11%. (24) 

Rectal examination is inexpensive, relatively noninvasive, and nonmorbid and can 

be taught to nonprofessional health workers; however, its effectiveness depends 

on the skill and experience of the examiner. The possible contribution of routine 

annual screening by rectal examination to reducing prostate cancer mortality 

remains to be determined. 

Transrectal Ultrasound and Other Imaging Tests 

Imaging procedures have been suggested as possible screening modalities for prostate 

cancer. Prostatic imaging is possible by ultrasound, computed tomography, and 

magnetic resonance imaging. Each modality has relative merits and disadvantages for 

distinguishing different features of prostate cancer. Ultrasound has received the most 

attention, having been examined by several investigators in observational settings.(25) 


Sensitivity ranged from 71% to 92% for prostatic carcinoma and 60% to 85% 

for subclinical disease. Specificity values ranged from 49% to 79%, and positive 

predictive values in the 30% range have been reported. The sensitivity and positive 

predictive value for ultrasound as a single test may be better than for rectal 

examination. The rate of cancer is extremely low among ultrasound-positive 

patients in whom rectal and PSA examinations are normal.(26) 

Contemporary prostate biopsy relies on spring-loaded biopsy devices that are either 

digitally guided or guided via ultrasound. TRUS guidance is the most frequently 

used method of directing prostate needle biopsy because there is some suggestion 

that the yield of biopsy is improved with such guidance.(27) 

With the virtually simultaneous clinical acceptance of TRUS, spring-loaded biopsy 

devices, and the proliferation of PSA screening in the late 1980s, the number of 

prostate cores obtained from patients with either an abnormal DRE or PSA was 

most commonly six, using a sextant method of sampling the prostate.(28) 

There is evidence that the predictable increase in cancer detection rates that would 

be expected by increasing the number of biopsy cores beyond six does occur; 

e.g., biopsies with 12 or 15 cores would increase the proportion of biopsied men 

having cancer detected by 30% to 35%.(29, 30) 

The extent to which such increased detection will reduce morbidity and mortality 

from the disease or increase the fraction of men treated unnecessarily is unknown. 

Prostate-Specific Antigen (PSA) 

The PSA test has been examined in several observational settings for initial 

diagnosis of disease, as a tool to monitor for recurrence after initial therapy, and 

for prognosis of outcomes after therapy. There is no PSA value below which a 

man can be assured that he has no risk of prostate cancer. Parameter estimates for 

this test include sensitivity in the range of 70%.(31) 

The potential value of the test appears to be in its simplicity, objectivity, 

reproducibility, relative lack of invasiveness, and relatively low cost. PSA has 

increased the detection rate of early-stage cancers, many of which may be curable 

by local-modality therapies.(32-35) 

Experience with repeat PSA screening suggests that tumors detected on follow-up 

examinations are of lower clinical stage and grade.(36) 

Although a cutoff value of 4.0 ng/mL is frequently used to prompt prostate biopsy, 

screening studies have demonstrated that lowering the PSA cutoff will substantially 

increase the number of cancers detected, particularly in African Americans.(37) 

An initial PSA lower than 2.5 ng/mL is associated with a very low risk of cancer 

detection within a 4-year follow-up.(36-38) 

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) is 

a multicenter, randomized, two-armed trial designed to evaluate the effect of 

screening for prostate, lung, colorectal, and ovarian cancer on disease-specific 

mortality. Enrollment began in November 1993 and concluded in June 2001. 

Participants were randomly assigned to the screening or control arm. A total of 

76,705 men were enrolled, 38,250 of whom were assigned to the screening arm. Of 

these, 34,244 men underwent an initial PSA and/or DRE screening examination. 

Compliance rates for PSA and DRE were roughly equivalent at 89%. More than 

99% of men who underwent screening with either PSA or DRE received both 

screening tests.(39) 

Table 1: Summary of Prostate, Lung, Colon and Ovarian (PLCO) Screening 

Trial Results 

Screening Test PSA DRE PSA or DRE 

Administered N0 (%) N0 (%) N0 (%) 

Number of Men 

Receiving Test 

34, 233 34, 115 34, 224 

Positive Test (%): DRE 

Suspicious for Cancer; 

PSA >4 ng/mL 

2, 717 (7.9) 2, 482 (7.3) 4, 801 (14.1) 

Biopsies (% of 

positives) 

1, 112 (40.9) 639 (25.7) 1, 510 (31.5) 

Prostate Cancer (% of 

biopsies) 

489 (44.0) 219 (34.3) 556 (36.8) 

Prostate Cancer (% of 

positives) 

489 (18.0) 219 (8.8) 556 (11.6) 

PSA: Prostate specific Antigen. DRE: Digital Rectal Examination 

Various approaches aimed at improving the performance of PSA in early cancer 

detection have been tested. None are clearly more accurate than total serum PSA 

levels, but these approaches are listed below. 

• Complexed PSA and percent-free PSA 

• Third-generation PSA 

• PSA density 

• PSA density of the transition zone 

• Age-adjusted PSA 

• PSA velocity 

Frequency of screening 

The optimal frequency and age range for PSA (and DRE) testing are unknown 

(40, 41). Cancer detection rates have been reported to be similar for intervals of 

1 to 4 years. (42) 

Table 2: American Cancer Society Recommendation 

Population Age Performing PSA, 

DRE 

Average risk ≥ 50 

Moderate high risk 

≥ 45 

(one first degree 

relative with prostate 

cancer


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HEPATOCELLULAR CARCINOMA 

Dr. Ayman Abdo, MD, FRCPC 

King Saud University, Riyadh 

Corresponding Author: Dr. Ayman Abdo, MD, AmBIM, FRCPC 

Consultant, Gastroentorology Division, College of Medicine 

Riyadh, Kingdom of Saudi Arabia 


Hepatocellular carcinoma (HCC) is the most common primary malignancy of 

the liver. It represents the fifth most common cancer and the third most common 

cause of cancer death worldwide(4). It has a variable geographical distribution 

around the world. The incidence in developing countries is two to three times 

higher than in Western countries. For example, in Eastern Asia and Middle Africa 

the age-adjusted incidence rate (AAIR) ranges from 20-28 cases per 10,000 in 

men while it is about 1-3 per 100,000 in Northern Europe, Australia and North 

America. In the United States the incidence of HCC has increased from 1.4 per 

100,000 population at the period from 1976-1980 to 2.4 per 100,000 population 

for the period from 1991-1995. 

In Saudi Arabia, according to the National Cancer Registry, liver cancer accounts 

for 6.1% of all newly diagnosed cancers according to the most recent cancer 

registry covering the years 1999-2000. HCC was the second most common cancer 

affecting Saudi males and the eighth most common cancer affecting females with 

an overall age standardized rate is 4.5/100,000 population. Male to female ratio is 

279:100. Of all liver cancers in Saudi Arabia, hepatocellular carcinoma accounts 

for 87.6% in Saudi Arabia. The median age at diagnosis is 65 years for males 

and 60 years for females. 

This incidence of HCC in Saudi Arabia is not surprising given the high prevalence 

of the two major risk factors, namely hepatitis B and hepatitis C infections. In the 

large epidemiologic study by Al Faleh et al, 7% of Saudi children were found to be 

positive for HBsAg. Not until universal vaccination was applied in Saudi Arabia 

did this prevalence rate decrease to less than 0.3%. Since the initial epidemiologic 

studies showing high prevalence of hepatitis B were done on children who are 

now adults and with an estimation that about 20% of these patients will probably 

develop cirrhosis with an annual risk of 1-4% for HCC, the incidence of HCC is 

expected to increase dramatically in the Kingdome in the next 30 years. Hepatitis C 

is also common in Saudi Arabia with a prevalence rate of 1-3% of the population, 

which further increases the risk of HCC. More recently, the incidence of hepatitis 

C seems to have decreased to about 1.1%. 

Risk Factors 

The development of cirrhosis is the major risk factor for the development of HCC 

regardless of the cause. The annual incidence of HCC in patients with compensated 

cirrhosis is about 3%. 

Hepatitis B is considered the strongest epidemiologic factor associated with HCC 

in the majority of countries but more importantly in Asia and Africa. The carrier 

state of hepatitis B early in life carries a lifetime relative risk of developing HCC of 

over 100, while the annual incidence of HCC in hepatitis B patients with cirrhosis 

exceeds 2%. Hepatitis C is considered the most important risk factor for HCC in 

Western countries and Japan. Almost all HCC in patients with hepatitis C occurs 

in patients who have developed cirrhosis in which the yearly incidence varies 

between 3 to 8 %. Other less likely risk factors include Aflatoxin B1 derived from 

Aspergillus flavus and Aspergillous parasiticus which is an important risk factor 

for HCC in parts of Africa and Asia, hereditary hemochromatosis and Wilson's 

disease. Because of the significant increase in the prevalence of diabetes and 

obesity, it is estimated that non alcoholic fatty liver disease may be an important 

risk factor for development of HCC in the future. 


The classic features of HCC include right upper quadrant pain and weight loss. 

Weakness, abdominal swelling, non specific gastrointestinal symptoms, and 

jaundice are other presenting features. Special clinical scenarios should raise the 

suspicion of HCC. This includes acute deterioration of liver function in a patient 

with stable cirrhosis, new onset ascites, and acute intra-abdominal bleeding. 

Physical findings vary according to the stage of the disease. If the tumor is small, 

no signs may be found except those related to cirrhosis. In more advanced disease, 

hepatomegaly is common with a possibility of feeling a mass or a hard irregular 

liver surface which may be tender. A bruit may be heard on the liver. Ascites is 

often found, most commonly as a result of the underlying cirrhosis leading to 

portal hypertension but rarely due to tumor invasion of the peritoneum. Muscle 

wasting is common and is usually progressive. 

Screening Methods 

Abdominal Ultrasound (US) 

While US has the advantage of being safe, commonly available, and cost -effective, 

its main disadvantage is its low specificity and its operator dependent nature. Newly 

discovered focal liver masses in patients with liver cirrhosis has a high likelihood 

of being HCC. Abdominal US is associated with a sensitivity and specificity of 

20-51% and 92-96%, respectively for detecting lesions consistent with HCC in 

patients with cirrhosis. Detection rates for lesions between 2 and 3 cm and 1 and 2 

cm with US are estimated to be as low as 20 and 13%, respectively. In spite of the 

limitations of US in diagnosing HCC, due to its low cost, safety, and availability, 

it is still considered the best first test to be performed when HCC is expected. 

Triphasic CT scan of the liver as well as MRI are the diagnostic tests of choice in 

patients with HCC. Some studies are utilizing these tests in screening purposes 

as well especially in high risk patients but high cost and radiation, in case of CT, 

are significant limiting factors. 

Serum Alfa fetoprotein (AFP) 

AFP is an alfa 1 globulin that is normally present in high concentrations in fetal 

serum but in only minute concentrations in adults. Reported sensitivities are 

around 39-65%, specificities around 76-94%, but a poor positive predictive value 

of 9-50%. In a recent systematic review it was confirmed that AFP has a poor 

diagnostic ability to detecting HCC at any level of pretest risk. However, as a 

confirmatory test in patients with a mass on imaging studies, AFP determination 

remains clinically useful. AFP elevation lower than 500 ng/mL may be seen in 

patients with active necroinflammatory changes in the liver secondary to active 

hepatitis. A progressively rising AFP level even at low concentrations is highly 

suggestive of HCC. Elevations above 1000 ng/mL have a high specificity rate. 

Other tumor markers are under investigation but none is ready for clinical use yet. 

These include Des-y-carboxy prothrombin and alfa-l-fucosidase. 

Summary of Management 

Different treatment modalities are available for patients with HCC. The decision 

on the best treatment modality should be based on the following factors: 

• The number of lesions 



• The size of lesions 

• The status of the underlying liver 

• The status of the portal vein 

• The patient’s performance status 

• The local expertise 

• The patient preferences 

Current available modalities include: liver transplantation, tumor resection, 

alcohol ablation, radiofrequency ablation, chemoembolization, radioembolization, 

chemotherapy or targeted therapy (Sorafenib). 

The approach for the management of HCC must be multi disciplinary where 

oncology, hepatology, liver transplantation, liver surgery, interventional radiology, 

and palliative care specialists are involved. 

Prevention 

Vaccination programs 

Vaccination is a very powerful measure to reduce the infection rate with hepatitis 

B and hence reduce the incidence of HCC. The nationwide hepatitis B vaccination 

program launched in Taiwan in 1984 led to a reduction of the hepatitis carrier rate 

in children from 10% to less than 1% and to a reduction in the incidence of HCC 

from 0.70 to 0.36 per 100,000 between 1986 and 1994. In Saudi Arabia, a routine 

hepatitis B vaccination of children was added as part of the extended program 

of immunization in 1989. A dramatic reduction was noted in the prevalence of 

hepatitis B from 6.7% in 1989 to 0.3% in 1997. No evidence is available yet on 

the effect of this reduction on the incidence of HCC. 

Treatment of viral hepatitis 

If cirrhosis is the most important risk factor for the development of HCC, could 

the incidence of HCC be reduced by preventing cirrhosis or treating cirrhosis due 

to viral hepatitis with antiviral therapy? Many studies in hepatitis B and hepatitis 

C show that treatment of active hepatitis, especially when successful, may lead 

to a reduction in the incidence of HCC. 

Screening 

Although many modeling data exist suggesting that screening can reduce HCC 

related disease specific mortality in a cost effective manner, there is only one 

randomized trial showing benefit while many other studies didn’t. In the study 

showing benefit from China, 18,816 patients where screened with 6 monthly 

AFP and ultrasound showing a reduced mortality rate by 37% in the screened 

arm even though the adherence to the surveillance was only around 60%. The 

screened population in this study was patients with current or previous exposure 

to hepatitis B. 

Patients who are best candidates for enrollment in a screening program include 

patients with cirrhosis for whatever reason. Patients who have hepatitis B without 

cirrhosis, especially if above 45 in age or have a family history of HCC may also 

be candidates. 

Most authorities (including the Saudi Gastroeterology Association) suggest 

screening with abdominal ultrasound and AFP every 6 months. Once a lesion is 

detected then a triphasic CT or contrast enhanced MRI is indicated for confirmation. 

In case of patients with cirrhosis who have a lesion larger than 2 cm detected by a 

contrast radiological study showing early arterial enhancement and rapid venous 

washout this is diagnostic for HCC and no further testing is recommended. If the 

lesion is less than 2 cm or the patient is not cirrhotic then a biopsy is indicated 

for confirmation. 

Outcome 

The natural history of HCC depends on the stage of the disease but is poor in the 

majority of cases. Tumor size at presentation is an important factor in the natural 

history but its use as a sole predicting factor is hindered by the fact that this tumor 

doubling time may in fact be very variable. In some patients the tumor growth is 

slow doubling in size in twenty months or more, while in others the tumor grows 

much faster and doubles in less that 1 month. In symptomatic patients in China 

and Africa, death usually occurs within four months, while some reports suggest 

a longer survival and a more indolent course in Western countries. The most 

important factor in determining the natural history of HCC patients is the stage 

of the underlying liver disease. 

Recommendation of Hepatocellular Carcinoma Prevention and Early Detection 

Population Category Recommendation 

Primary Prevention General population - Hep B vaccination 

- Prevention of hepatitis 

- Avoidance of alcohol 

Patients with hepatitis - Treatment of hepatitis 

Patients with cirrhosis Early detection Alpha feto protein and 

liver ultrasound every 6 

months 

References 

1. J Bruix, M Sherman. Management of hepatocellular carcinoma. Hepatology 

2005; 42(5):1208-1236. 

2. Kingdom of Saudi Arabia ministry of health, National Cancer Registry (1997- 

1998). 2001. 

3. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable 

hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 

2003; 37(2):429-442. 

4. Chang M, Chen C, Lai M, Hsu H, Wu T, King M. Universal hepatitis B vaccination 

in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J 

Med 1997; 336:1855-1859. 

5. Liaw Y, Sung J, Chow C, Farrell G, Lee C, Yuen H et al. Lamivudine for 

patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 

35:1521-1531. 

6. Zhang B, Yang B, Tang Z. Randomized controlled trial of screening for 

hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130:417-422. 

7. Abdo A et al. Saudi Gastroenterology Association guidelines for the diagnosis 

and management of hepatocellular carcinoma, summary of recommendations. 

Annls Saudi Med 2006, 26: 261-265 

8. Llovet J et al. Sorafoneb in advanced hepatocellular carcinoma. NEJM 

2008,359:378-90 


CANCER PREVENTION AND EARLY DETECTION IN CHILDREN 

MALIGNANCIES 

Reem Al Sudairy, MD 


Corresponding Author: Reem Al Sudairy, MD 



E-mail: sudairyr@ngha.med.sa 

Abstract 

Objectives: Cancer in children is rare disease. It accounts for about 1% of all 

malignancies, and as a result, understanding of the factors causing childhood 

cancer is less well defined compared to that for adults. Medical research has 

contributed greatly to improved treatment outcome in childhood cancer, reaching 

cure rates up to 80%. However, little progress has been made in prevention of 

childhood cancer. This manuscript summarizes the early detection and prevention 

guidelines for children. 

Methods: Review of the literature and international pediatric oncology 

recommendations about childhood cancer prevention and early detection are 

reviewed and summarized. 

Results: Genetic predisposition can cause up to 10% of all childhood malignancies. 

This important risk factor will be discussed in details with emphasis on 

recommendations for genetic testing and follow up of those children by the 

primary care physicians. 

Environmental / external factors in relation to childhood cancer will be also 

reviewed with updated information on current research pertinent to this important 

risk factor. Recommendations to pediatricians and primary care physicians 

concerning early detection and prevention of childhood malignancies in at risk 

population will be also discussed. 

While there is still a knowledge gap in the field, there are certain clinical situation 

where early detection and prevention will help in the control of childhood cancer. 

Introduction 

Cancer in children is rare and accounts for about 1% of all malignancies and as a 

result the precise causes of childhood cancers are still insufficiently known, and they 

are less well defined compared to that for adults. Childhood Cancers is typically 

of different variety from those observed in adults. The carcinogenic process in 

children is much shorter in time. In children cancers are mainly mesenchymal / 

neural in origin while in adults they are mainly epithelial and in internal organs 

and have a strong and proven link to environmental factors. 

Incidence 

Approximately 149 of every 1 million children under the age of 20 years are 

diagnosed with cancer each year in the United States. Acute leukemia accounts 

for the greatest proportion of new cancer cases (25-30%) followed by brain tumors 

(20%) and lymphomas (15%). (1) 

According to the Saudi Cancer Registry 2004 statistics, the total incident cases 

reported among children (0-14 years) were 713 which represent 7.6 % of the 

total number of cancers in Saudi Arabia. Of all the cases reported, there were 

584 Saudis. (2) 

Although the incidence of pediatric cancer is low, its significance is of great 

importance. In KSA in 2007 approximately 40% of the Saudi population was under 

15 years which put a large number of the population at risk of childhood cancer. 

Childhood Cancer Symptoms 

The symptoms of childhood cancer depend on the site and the extent of the tumor. 

Leukemia can cause anemia, bleeding, fever, bone pain and lymph nodes, spleen, 

liver enlargement. Most of other tumors produce symptoms related to their position 

either in the form of a lump or because it impairs the function of one or more organs. 

Most of children with cancer are treated at pediatric cancer centers per national 

clinical protocols. Surgery, chemotherapy, radiotherapy are the mainstay of 

treatment for most childhood cancers. Bone marrow and peripheral stem cell 

transplantation is another important modality of therapy in some cases. 

Outcome 

Although cancer still represents the second most common cause of death in children 

(following accidents), the survival rate from children cancer have improved 

substantially in the last 30 years and had risen to over 75% due to improvement in 

treatment modalities. There is a relative greater improvement in the young age group 

(under 15 years) in comparison to older children (15-19 years of age). Although 

disease biology may play a role in this difference in outcome, failure to treat 

older children on national protocols plays a major role in their inferior outcome. 

Risk Factors 

The precise causes of many childhood cancers are still not well understood but 

they are assumed to be multi-factorial. The two most important risk factors are: 

1. Genetic predisposition. 

2. Environmental factors (Inutero and during early childhood). 

Genetic pre-disposition to Cancer 

A large number of predisposing syndromes exist and account for up to 10% of 

all childhood malignancies. Most syndromes are associated with a germ line 

mutation in a single gene (e.g. RB1) however; in some syndromes (e.g. Wilm’s 

Tumor) several genetic loci have been involved. Polymorphism of certain genes 

loci have been shown to play a role in cancer development. (3) 

Table 1 shows the genetic conditions predisposing to cancer in children. It is 

the responsibility of the pediatricians/family physician’s to be able to recognize 

clinically cancer-predisposing syndromes, and should strongly suspect the presence 

of cancer-predisposing condition from the family history (earlier age of cancer 

onset, bilateral or multifocal tumors, and multiple primary malignancies of 

different types in the same individuals). The presence of certain physical signs in 

parent should also alert physicians, like café-au-lait spots and axillary freckling 

(Neurofibromatosis type1). All at risk children should be referred to a trained 

genetic counselor and should be followed up regularly by their pediatrician/ 

family physician. 



Table 1: The genetic conditions predisposing to cancer in children. 

No. Disease Inheritance Most common cancers 

1. Ataxia telangiectasia Recessive Leukemia, Lymphoma 

2. Beckwith-Wiedemann syndrome Complex Wilms’ Tumor, Hepatoblastoma, Adrenal carcinoma. 

3. Bloom’s Syndrome Recessive Leukemia, Lymphoma, Epithelial Cancers, Hepatocellular Carcinoma, 

Sarcomas, Brain Tumor. 

4. Familial Adenomatous Polyposis Dominant Colorectal Carcinoma, Hepatoblastoma, Thyroid Cancer, Medulloblastoma. 

5. Fanconi Anemia Recessive Leukemia, Squamous Cell carcinoma and Gastrointestinal and 

Genitourinary Tract Tumors. 

6. Juvenile Polyposis Dominant Gastrointestinal tumors 

7. Li-Fraumeni Syndrome Dominant Soft tissue sarcomas,Osteosarcoma, Breast cancer, Brain tumors, 

Adrenocortical carcinoma, Leukemia. 

8. Multiple endocrine neoplasia, type 1 Dominant Pancreatic islet cell tumor, Pituitary and Parathyroid adenoma. 

9. Multiple endocrine neoplasia, type 2 Dominant Medullary thyroid carcinoma, Pheochromocytoma, Parathyroid hyperplasia. 

10. Neurofibromatosis, type 1 Dominant Neurofibromas, Optic pathway gliomas, Leukemia, Malignant peripheral 

nerve sheath tumors. 

11. Neurofibromatosis, type 2 Dominant Vestibular Schwannoma 

12. Nijmegen breakage syndrome Recessive Lymphoma, Medulloblastoma, Glioma. 

13. Nevoid basal cell carcinoma syndrome Dominant Medulloblastoma, basal cell carcinomas. 

14. Peutz-Jeghers syndrome Dominant Intestinal tumors, Gastric and Pancreatic canceras, Gonadal tumors. 

15. Retinoblastoma Dominant Retinoblastoma, Osteosacoma. 

16. Rhabdoid predisposition syndrome Dominant Rhabdoid tumor, Medulloblastoma, choroid plexus tumor 

17. Rothmund Thomson Syndrome Recessive Skin and Bone tumors. 

18. Simpson Golabi Behmel Syndrome X-linked Recessive Wilms’ Tumor, Hepatoblastoma. 

19. Sotos syndrome Dominant Sacrococcygeal teratoma, Neuroblastoma, Leukemia, Lymphoma, Wilms’ 

Tumor 

20. Tuberous Sclerosis Dominant Central Nervous System tumors, Hamartomas, Renal angiomyolipoma, 

Renal cell carcinoma. 

21. Von Hippel-Lindau syndrome Dominant Retinal and Central Nervous System Hemangioblastoma, 

Pheochromocytoma, Renal cell carcinoma. 

22. Werner Syndrome Recessive Osteosarcoma, Menigioma, Melanoma, Thyroid carcinoma. 

23. Wilm’s Tumor Syndromes Dominant Wilms’ Tumor. 

24. Xeroderma pigmentosum Recessive Skin cancer, Leukemia 

25. X-linked lymphoproliferative disease X-linked Recessive Lymphoma 

Genetic testing is not a standard of care for all of the syndromes associated with 

pediatric malignancies, but in some of these syndromes where there is an increase 

risk of development of cancer during childhood; there is increasing evidence in 

the literature that using genetic testing and cancer surveillance has enhanced the 

long term outcome for affected patients. (3, 4, 5) 

American Society of Clinical Oncology (ASCO) issued a statement update on 

genetic testing for cancer susceptibility in 2003. The following are some of the 

recommendations that were made: (6) 

1-Indications for genetic testing: 

• The individuals have personal or family history features suggestive of a 

genetic cancer susceptibility condition. 

• The test can be adequately interpreted. 

• The results will aid in diagnosis or influence the medical or surgical 

management of the patient of family members at hereditary risk of cancers. 

2-Special issues in testing children for cancer susceptibility 

• ASCO recommends that the decision to offer testing to potentially affected 

children should take into account the availability of evidence-based riskreduction 

strategies and the probability of developing a malignancy during 

childhood. 

• Where risk-reduction strategies are available or cancer predominantly 

develops in childhood, ASCO believes that the scope of parental authority 

encompasses the right to decide for or against testing. 

• In the absence of increased risk of childhood malignancy, ASCO recommends 

delaying genetic testing until an individual is of sufficient age to make an 

informed decision regarding such tests. 

• The clinical cancer genetics professional should be advocate for the best 

interests of the child. 

3-Counseling pre- and post-test: 

ASCO recommends that genetic testing only be done in setting of pre and posttest 

counseling, which should include discussion of possible risks and benefits of 

cancer early detection and prevention modalities. 


Tumor Surveillance for Children with Cancer Predisposing Syndromes 

Unfortunately in children (in contrast to adults), only few guidelines for surveillance 

have been established and their benefit has been proven. The following are 

some examples of inherited cancer predisposing syndromes that have established 

pragmatic surveillance guidelines that are based on available evidence from large 

studies. 

Retinoblastoma (RB) 

It is a malignant tumor of the embryonic cells of the retina. It accounts for up to 4% 

of all childhood cancers. It occurs in heritable form (40%) where it will be usually 

bilateral or multifocal in younger patients (median age 11 months), and it occurs in 

nonheritable form (60%) where it will be unilateral in older patients (median age of 

22 months). Approximately 90% of RB cases are diagnosed by the age of 5 years. 

• It is recommended that children at risk of RB (including those with germ line 

RB1 gene mutation, as well as their offspring or siblings) should undergo 

ophthalmologic examination under general anaesthesia starting at birth. 

Recommendation for screening intervals and length of follow-up vary, but 

most experts recommend frequency of every 2-3 months until the age of 2 

years by which time 90% of heritable RB occur, after that frequency will be 

spaced to every 4-6 months until fourth to fifth year of life. (3,4,7) 

• To screen for pineal tumors, children should undergo MRI examinations of 

the brain every 6 months until the age of 5 years. (4,8) 

• No standard screening protocols for secondary tumors. 

Beckwith-Wiedmann Syndrome (BWS) and Idiopathic Hemihypertrophy 

(IHH) 

BWS is a congenital disorder of growth regulation characterized by macroglossia, 

macrosomia, ear anomalies, abdominal wall defects and neonatal hypoglycemia. 

In patients with BWS/IHH tumor surveillance is recommended. It should be 

targeted at Wilms’ tumor (the commonest childhood tumor of the kidney) and 

Hepatoblastoma. (9, 4, 10) 

The following should be performed on regular intervals: 

• Renal ultrasound, every 3 months until the age of 8 years. 

• Liver ultrasound, every 3 months until the age of 4 years. 

• Measurements of serum alpha feto protein (AFP) every 3 months until the 

age of 4 years. 

Wilms’ Tumor Associated Syndromes 

There are several genetic syndromes other than BWS/IHH which might predispose 

to Wilms’ tumor like WAGR syndrome, Denys-Drash syndrome, Familial Wilms’ 

tumor, Perlman syndrome, Fanconi anemia, Frasier syndrome and Simpson-Golabi- 

Behmel syndrome. Screening by ultrasound abdomen should be performed to 

those patients every 3 – 6 months as they have > 5% risk of Wilms' tumor (10,11) 

until the age of 5 years as it will detect 90-95% of tumors in patients with WT1 

gene mutation (10,4). 

Multiple Endocrine Neoplasia (MEN disorders) 

MEN disorders are cancer family syndromes that affect different endocrine organs. 

• MEN1 mutation carriers should be screened by annual serum calcium, 

parathyroid hormones, fasting glucose, insulin, prolactin and insulin growth 

factor 1. They should also have MRI examinations of the brain to assess the 

anterior pituitary gland every 3 years. (5) 

• MEN2 mutation carriers, all children should receive a prophylactic 

thyroidectomy early in life. (3,5) 

Familial Adenomatous Polyposis (FAP) 

FAP mutation carriers should be screened by annual colonoscopy beginning 

between the age of 10 and 14 years. If Polyps are found, colectomy should be 

performed using modern surgical techniques that preserve fecal continence. (3, 

12, 13) 

Von Hippel-Landau Disease (VHL) 

VHL is characterized by the development of proliferation of blood vessels 

in the retina, cerebellum or the spinal cord. It is characterized by cerebellar 

hemangioblastoma, retinal angioma, renal cell carcinoma and pheochromocytoma 

and other visceral tumors. Diagnosis usually occurs during early adulthood. 

Based on National Institute of Health-USA recommendations, patients and 

individuals at risk of VHL should receive an annual ophthalmologic examination 

from 1 year of age, annual urine catecholamine measurements from 2 years of 

age, enhanced MRI examination of the brain and spine every 2 years starting at 11 

years of age and then every 3-5 years after the age of 60 years, annual abdominal 

ultrasound beginning at 11 years of age, and abdominal CT scan every 1-2 years 

after the age of 20 years. Additionally, regular complete physical examination 

is suggested for detection of early abnormal cerebellar and spinal cord signs. 

(3, 14, 15) 

For the other cancer predisposing syndromes, there are no clear, widely used, 

standard surveillance protocols in the literatures. 

Environmental/External Factors 

Cancers are assumed to be multi-factorial diseases that occur when a complex 

and prolonged process involving genetic and environmental factors interact in a 

multistage sequence. In the last few decades, environmental linkages have been 

actively investigated and described, but the evidence for causal association is still 

in the primary stages especially in the field pediatric oncology. Etiological studies 

have often been concerned with exposures occurring during the mother’s pregnancy 

although pre-conception and post natal factors have also been investigated. 

Numerous environmental exposures have been linked with childhood cancer. 

Interpretation is limited by study designs (retrospective, case control studies), 

variation in the timing of exposure ranging from before conception to during the 

child’s lifetime, the wide range of cancers studied and most importantly the small 

numbers of patients affected with such a rare disease. 

In 2004 International Childhood Cancer Cohort Consortium (I4C) was proposed 

and since then it has progressed steadily. The purpose of the Consortium is 

the prevention of childhood cancer using evidence from prospective children’s 

cohort studies around the world. They are trying to advance understanding of 

the etiology and carcinogenic mechanisms in relation to childhood cancer. The 

study has 11 participating cohorts form 9 countries around the world with about 

700,000 subjects. (16, 17) 

Antenatal priority domains of interest for I4C outcomes are parental occupation/ 

type of work, smoking/drug use (mother/father, passive (maternal)), diet (fish, 



seafood and yogurt), radiation exposure, pesticide/chemical exposure, maternal 

infection, sun exposure/Vitamin D, supplements during pregnancy and folate intake. 

For children, postnatal priority domains include: Anthropometry, infectious up to 

1 year, radiation exposure, feeding habits, sun exposure, passive smoking, atopy 

/asthma. The reader is referred to an excellent review on environmental linkages 

for childhood cancer. (18) 

From that review, environmental factors that had a conclusive evidence (cause 

and effect are undoubtedly linked with evidence of a dose-response trend) were : 

high-dose ionizing radiation linked to thyroid cancer, prenatal diethylstilboestrol 

linked to vaginal adenocarcinoma and tobacco smoke linked to lung cancer 

during adulthood. 

Other environmental factors with compelling evidence (substantial data linking 

cause and effect but with no consistent evidence of a dose-response trend and/or 

evidence confirming timing and dosing of exposure) were: diagnostic radiographs, 

industrial air pollution, solar UV radiation and viral agents. 

There was inconclusive evidence (extensive studies have produced inconsistent 

results) that other environmental factors were linked to childhood cancer like: 

residential proximity to nuclear facilities, extremely low-frequency electromagnetic 

field (ELF-EMF), traffic-related air pollution, hot dogs and parental occupational 

exposures. Until conclusive evidence is available on environmental factors it is 

recommended that: Parents should avoid exposure to substances that are known 

or suspected carcinogens, and this advice holds during pregnancy and at all 

stages of life. Behaviors that might enhance protection against cancer in offspring 

include taking multivitamin supplements during pregnancy, breast feeding as long 

as possible. Children should avoid exposure to various carcinogens. Instilling 

healthy lifestyle choices such as optimizing the child’s dietary intake of fibers, 

fruits and vegetables, exercise and dietary moderation during childhood lays an 

important foundation for long-term cancer prevention. Focusing on children and 

young adolescents in primary prevention is very important as it is easier to teach 

healthy behaviors at a young age rather than modify behaviors at later age. (19, 20) 

Physicians should avoid performing unnecessary diagnostic radiographs. 

Long Term Follow-up Guidelines for Survivors of Childhood, Adolescent 

and Young Adult Cancers 

The improvement in survival rates in children with cancer resulted in a growing 

population of childhood cancer survivors. The use of cancer therapy at an early 

age can produce long term complications, such as impairment in growth and 

development, neurocognitive deficits, cardiac, pulmonary, gastrointestinal, renal, 

endocrine and gonodel dysfunction as well as second malignant neoplasms. (21) 

Several studies following up large cohorts of survivors of childhood cancers 

reported 3-10 fold increased risk for second malignancies in comparison with 

general population, which are a leading cause of non-relapse- related late mortality. 

(22) 

Second malignancies in childhood survivors vary depending on the type of 

therapy received and the presence of genetic predisposition. They are classified 

into two groups: (22) 

• Therapy-related myelodysplasia/acute myeloid leukemia, which is 

characterized by short latency (approximately 3-5 years from primary 

cancer diagnosis) and exposure to alkylating agents and/or topoisomerase 

II inhibitors. 

• Therapy-related solid tumors, which has a strong and well-defined association 

with radiation and characterized by latencies that exceed 10 years. 

Guidelines For Screening Childhood Cancer Survivors: The Children’s 

Oncology Group (COG) developed risk-based exposure related clinical practice 

guidelines[Long-Term Follow-Up Guidelines for survivors of childhood, 

adolescent, and young adult cancers (COG-LTFU) ] for screening and management 

of late effects resulting from therapeutic exposures used during treatment for 

pediatric malignancies. 

Those guidelines were developed collaboratively by the COG Nursing Discipline 

and Late Effects Committee. They represent a statement of consensus from a panel 

of experts in late effects of pediatric cancer treatment. The recommendations 

are based on thorough review of the literatures as well as the collective clinical 

experience of the taskforce members, panel of experts and multidisciplinary 

review panel (including nurses, physicians, behavioral specialists and patient/ 

parent advocates). 

The Guidelines and the Health Links can be downloaded from www.survivorship. 

guidelines.org 

Table 2: Selected exposure-based screening recommendations (Children’s 

Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines). 

Category Therapeutic Potential Late Recommended 

Exposure Effect Screening 

Second Etoposide Acute Myeloid CBC, platelet, 

Malignancies Teniposide Leukemia differential yearly for 

10 years following 

exposure 

Alkylating Acute Myeloid CBC, platelet, 

Chemotherapy Leukemia/ differential yearly for 

Anthracyclines Myelodysplasia 15 years following 

exposure 

Radiation (any Second Yearly history and 

field) Malignant physical exam with 

neoplasm inspection and 

(SMN) in palpalation of tissues in 

radiation field 

(skin, bone, 

soft tissue) 

radiation field. 

Radiation 

impacting the 

thyroid 

Thyroid Cancer Yearly thyroid exam 

Radiation Breast Cancer Monthly breast exam 

impacting the 

Clinician breast exam 

breast 

yearly until age 25, then 

every 6 months 

Mammogram yearly 

beginning 8 years after 

radiation or at age 25, 

whichever comes last. 

Radiation Colorectal Colonoscopy every 10 

impacting the Cancer years beginning 10 years 

colon 

following radiation or 

at age 35, whichever 

comes last 


Pediatric Cancer Prevention and Early Detection Guidelines 

Intervention Population Procedure Frequency Starting Age Stopping Age 

Primary Parents Avoid exposure to substances that are known or N/A N/A N/A 

Prevention 

suspected carcinogens 

Multivitamins supplement during pregnancy N/A N/A N/A 

Breast feeding as long as possible N/A N/A N/A 

Children Avoid exposure to various carcinogens N/A N/A N/A 

Instilling healthy lifestyle choices N/A N/A N/A 

Physicians Avoid performing unnecessary diagnostic 

radiographs. 

N/A N/A N/A 

Screening General Public 

Special Population 

N/A N/A N/A N/A 

Screening Retinoblastoma (RB) 1. Opthalmologic examination under general 

anaesthesia 

every 2-3 months 

till age of 2 years 

then every 6 

months 

Till age of 4 years 

at birth 4-5 years 

2. Screen for pineal tumors, do MRI brain Every 6 months At birth 5 years 

Beckwith-Wiedmann Syndrome and 

Idiopathic Hemihypertrophy (IHH) 

1. Renal ultrasound every 3 months Diagnosis 8 years 

2. Liver ultrasound every 3 months Diagnosis 4 years 

3. Measurement of serum AFP every 3 months Diagnosis 4 years 

Wilms' Tumor Associated Syndromes 1. Abdominal Ultrasound every 3-6 months Diagnosis 5 years 

Multiple Endocrine Neoplasia (MEN 

Disorders) 

MEN 1 Mutation Carriers 

1. Serum Calcium, parathyroid hormones, 

fasting glucose, insulin, prolactin and insulin 

growth factor 1. 

every year Diagnosis indefinite 

2. MRI examinations of the brain to assess the 

anterior pituitary gland. 

MEN 2 Mutation Carriers 

every 3 years Diagnosis indefinite 

1. Prophylactic thyroidectomy early in life N/A N/A N/A 

Familial Adenonatous Polyposis 

(FAP) 

1. Colonoscopy every year 10-14 years indefinite 

Von Hippel-Landau Disease (VHL) 1. Ophthalmologic examination every year 1 year of age indefinite 

2. Urine Catecholamine measurements every year 2 years of age indefinite 

3. MRI examination of the brain and spine every 2 years 11 years of 

age 

60 years 

every 3-5 years 60 years indefinite 

Survivors of childhood Cancer Refer to Table 2 for details of screening recommendations 

References 

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Poplack D, editors. Principles and practice of pediatric oncology. 6th edition. 

Philadelphia: Lippincott, Williams and Wilkins; 2006. P. 1-13. 

2. Saudi Cancer Registry, Cancer incidence Report, 2004. Page 24. 

3. Pakakasama S, Tomlinson GE. Genetic predisposition and screening in 

pediatric cancer. Pediatric Clinic of North America-volume 49, issue 6(Dec. 

2002):1393-1413. 

4. Rao A, Rothman J, Nichols KE. Genetic testing and tumor surveillance for children 

with cancer predisposition syndromes. Current Opinion in pediatrics 2008, 20:1-7. 

5. Strahm B, Malkin D, Hereditary cancer predisposition in children: Genetic 

basis and clinical implications. Int J Cancer 2006; 119:2001-2006. 

6. American Society of Clinical Oncology policy statement update: Genetic 

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screening for familial retinoblastoma be stopped? A register based study 1945- 

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8. Kivela T. Trilateral retinoblastoma: a meta-analysis of hereditary 

retinoblastoma associated with primary ectopic intracranial retinoblastoma. J 

Clin Oncol 1999; 17:1829-1837. 



9. Tan TY, Amor DJ. Tumor surveillance in Beckwith-Wiedemann syndrome and 

Hemihyperplasia: A critical review of the evidence and suggested guidelines for 

local practice. J Pediatr Child Health 2006; 42:486-490. 

10. Scott RH, walker L, Olsen OE,et al. Surveillance for Wilms' tumor in at-risk 

children: pragmatic recommendations for best practice. Arch Dis Child 2006; 

91:995-999. 

11. Scott RH, Stiller CA, Walker L, et al. Syndroms and constitutional 

chromosomal abnormalities associated with Wilms' tumor. J Med Genet 2006; 

43:705-715. 

12. Hyer W, Fell JM. Screening for familial adenomatouse polyposis. Arch Dis 

Child 2001;84:377-80. 

13. Plon SE, Malkin D. Childhood cancer and heredity. In: Pizzo P, Poplack D, 

editors. Principles and practice of pediatric oncology. 6th edition. Philadelphia: 

Lippincott, Williams and Wilkins; 2006:24. 

14. Plon SE, Malkin D. Childhood cancer and heredity. In: Pizzo P, Poplack D, 

editors. Principles and practice of pediatric oncology. 6th edition. Philadelphia: 

Lippincott, Williams and Wilkins; 2006:27-28. 

15. Singh AD, Shields CL, Shields JA. Von Hippel-Lindau disease. Surv 

Ophthalmol 2001; 46:117-42. 

16. Brown RC, Dwyer T, Kasten C, ET al.Cohort profile: The International 

Childhood Cancer Cohort Consortium (I4C). Int J Epidemiol 2007; 36:724-730 

17. Second International Childhood Cancer Cohort Consortium 

Workshop. August 29-30, 2007.www.nationalchildrensstudy.gov/research/ 

internationalinvolvement/pages/I4C-workshop-083007-101107. 

18. Buka I, Koranteng S, Vargas ARD. Trend in childhood cancer incidence: 

Review of Environmental Linkages. Pediatr Clin N Am 2007; 54:177-203. 

19. Pollock BH, Knudson Jr. AG. Preventing cancer in adulthood: Advise 

for pediatrician. In: Pizzo P, Poplack D, editors. Principles and practice of 

pediatric oncology. 6th edition. Philadelphia: Lippincott, Williams and Wilkins; 

2006:1617-1628. 

20. Selvan MS, Kurpad AV. Primary prevention: why focus on children & young 

adolescents? Indian J Med Res 120, Dec. 2004, pp 511-518. 

21. Bhatia S. Cancer survivorship---Pediatric issues. American Society of 

Hematology (ASH) educational book, 2005. P.507-515. 

22. Bhatia S. Secondary Malignancies: What, When, Why, in Whom? NCCN 

clinical practice oncology forum 2008. www.medcsape.com/viewarticle/581683 

ROLE OF PRIMARY CARE PHYSICIAN FIGHT AGAINST CANCER 

Farrah, M. 

Corresponding Author: Consultant Family Medicine & Primary Health Care 

Department of Family Medicine & Primary Health Care 

National Guard Health Affairs, King Abdulaziz Medical City 


Abstract 

Background: Primary Care Physician (PCP) represents the first line in the fight 

against cancer for many reasons. Enhancing the roles of the PCPs will help in 

saving more lives from cancer related causes. 

Methods: The role of the PCP in the cancer prevention and early detection of 

cancer were identified and summarized. The advantages of primary care physicians 

were enlisted. 

Results: PCP can play an important role in increasing the patient awareness 

and knowledge about cancer, help in decreasing the risks for preventable 

cancers and perform early detection for common cancers which will save lives. 

Recommendations for specific cancers are summarized. 

Conclusion: Enhancing the role of the primary care physicians in the fight 

against cancer is important due to certain advantages possess by them that can 

be better utilized. Physicians should incorporate cancer control activities into 

their routine practice. 

Introduction 

The structure of the current healthcare system is designed in such a way that it 

is largely dependent on the care seeking behavior of the patient, who initiates 

his or her care by the natural sensors in the body. A person would ask for help 

when a disease becomes symptomatic. Despite advances in technology and our 

knowledge that can detect some diseases even before symptoms appear, the care 

delivery system still lags behind in its metamorphosis. Even though radical changes 

are needed in the existing healthcare organizations to fully adapt to advances in 

knowledge, there is some overlap in the alignment of disease pathogenesis with 

the current levels of care. 

Primary care is where most diseases including cancer are first encountered. Care 

is further channeled to secondary and tertiary level for those who need it. The 

physicians working at the primary care have several advantages in applying some 

of the advances in technology and knowledge that relates to prevention and early 

detection of cancer. These advantages for the primary care physician are by default 

of existing design of care delivery system and with these come responsibilities 

that lie squarely on the primary care physicians. 

Advantages For Primary Care Physician 

First Contact 

The primary care physicians work at the frontline of any healthcare organization. 

These are either family medicine specialists or the non-specialist general 

practitioners. The primary care physicians work in solo or group practice and 

are mostly linked to tertiary care organizations. The primary care doctor is the 

first medical expert that the patient comes in contact with which allows for early 

detection of cancer. 


Opportunity 

Patients also seek counsel of their primary care physicians for problems other 

than cancer, this provides with the opportunity to screen for cancer early when 

it is not yet a problem for the patient to seek help for. Having a database of all 

normal patients who only seek help for smaller problems e.g. for an occasional 

upper respiratory tract infection, allows for the primary care physician to reach 

those with no symptoms of cancer by call-recall one by one. 

Wider Scope of Cancer Coverage 

The broader scope of work of the family physician allows them to cover screening 

for all screenable cancers, instead of being limited to cancer of one specialty or 

another. 

Multiplicity of Visits 

Patients have the most frequent interaction with their family physicians each 

year, than with any other specialty. Most cancer prevention screening procedures 

require no less than an annual follow-up. 

Family Network 

Being the family doctor for the whole family of the patient needing cancer 

prevention advice or screening, the primary care physician has several opportunities 

to alert and convince the family members to engage in cancer prevention screening 

for their other family members. 

Whole Family Coverage 

The visitors to family doctor are not limited by age or gender, therefore preventive 

coverage for cancers in all ages and genders can be initiated in the primary care 

setup. A person can be a patient of a family doctor for his or her lifetime. Family 

doctors often provide care to the next generation of their patients as well. 

Long Term Trust 

Having long-term relationship of trust with the patients and their families, the 

primary care physician is ideally placed to impart health education quickly, easily, 

with little resistance and with greater impact on the patient. 

Multi disciplinary Team Support 

The primary care physician's working team of nurses, health educators and others 

are as versatile as the scope of family practice to assist in managing the prevention 

of all cancers. Initiating the cancer screening for the patient is a simple process, 

based on age and gender and nursing staff at the primary care level have played 

a crucial role in several healthcare setups in this regard. Health educators do the 

counseling for cancer prevention where physicians are sometimes limited by 

their busy schedules. 

Coordination of Care 

The primary care physicians being in the role of classic gate-keeper, can coordinate 

the care of all types of cancers with the specialties that a patient may need referral 

to, thereby facilitating prompt treatment. 

Community-link 

The family doctors also have the most direct link with the community to which 

the patient belongs, which by default allows them to be in a leadership position to 

mobilize communities towards cancer prevention. Primary prevention for many 

cancers start with health promotion activities at the community level and no one 

is better suited than the family medicine physician for the job. 

Home-visits 

The family physicians and their team members are often the direct providers of 

home health care, placing them at a key position in completing the loop of home 

based cancer care of tertiary prevention, i.e. rehabilitation and palliative care. 

Role Expectations In Fight Against Cancer 

Being in the position of several advantages within the existing healthcare structure, 

the primary care physician is expected to take the lead role in several aspects of 

the fight against cancer, particularly in the arenas of primary prevention (health 

promotion and specific protection) and secondary prevention (screening). Family 

physicians are ideally positioned to implement clinical prevention guidelines for 

cancer. Their experience and feedback would be vital for the guidelines to have 

a successful pragmatic outcome. The roles of the primary care physicians are 

given below as general and specific as these relate to cancer. In addition the future 

roles and expectations are also described based on technological advances and 

anticipated changes in healthcare systems. 

General Role 

Guideline & Program Development 

Any guidelines developed or planning carried out at national, regional or local 

level would require the input of the representatives of family physician to develop 

and improve the implementation section of the guidelines or programs designed 

for cancer prevention. 

Primary Prevention 

Advocacy 

This role is not exclusive to the primary care physicians but they should not fall 

behind in advocating and raising awareness through news papers, magazines, 

television, radio and other mediums / forums of communicating with the public and 

the decision making bodies, such as government, non-governmental organizations, 

businesses and others who have the resources to bring change in healthcare delivery 

system and the attitudes about cancer 

Community Mobilization 

This requires that the primary care physician extends his/her influence as a 

healthcare professional beyond the boundaries of the clinic and into the local 

community from which s/he draws practice. This measure is two-fold; first is 

recruiting of patients to form volunteer groups who believe in promoting healthier 

lifestyle in the community and also harnessing support of the local community 

leaders, followed by carrying out promotion activities ranging from distribution 

of brochures to holding health festivals etc. 

Clinic Based Health Promotion 

These can be carried out at the clinic level, providing individual and group 

counseling for promoting smoking cessation and discouraging other risky 

behaviors. Health educators and dietitians can have a stronger role in this regard. 

Specific Protection 

This role is at present limited to the provision of vaccination in the clinic for 

protection against human papilloma virus, the causative agent for cervical cancer 

in women and hepatitis vaccinations? 

Secondary Prevention 

Early Detection: Screening 

Several cancers can be detected early. For many of the cancers there is a component 



of patient education on being made aware of the early signs of cancer and self 

examination. Screening of cancers requires physical examination by physician, 

while others require a specific procedure such as Pap smear or a diagnostic 

laboratory or radiology test. Depending on resources such screening facilities may 

or may not be available at the primary care level and may the family doctor may 

have to refer a patient to a tertiary care facility to get these done. 

Prompt Treatment Referral: 

The primary care physician is ideally suited to refer a patient for confirmation 

of a screening result by additional diagnostic workup and for prompt referral to 

access treatment. 

High risk Patient Monitoring 

Monitoring of patients with family history of cancer or with other evidence of 

higher risk can be better followed up by the primary care physician, once the 

high risk is established. 

Tertiary Prevention 

Rehabilitation & Palliative care 

Having a trusted long term relationship with the patient and his/her family the 

primary care physician can be instrumental in the decisions and care process of 

those diagnosed with cancer, particularly in rehabilitation and palliative care. 

This can be more effective if the primary care setup is advanced to cover home 

health services. 

Cancer Specific Roles 

This section highlights the role of the primary care physician limited to the 

activities in the clinic. The additional roles as described above in the general role 

section still apply. 

The family doctor office would require some operational changes to be effective 

in clinical prevention: 

1. Having a database (electronic or register) of patients under care and to be 

able to contact them by a calling system or an SMS system to come for 

preventive checkup is critical. 

2. Incorporation of information technology can be very useful in alerting 

patients and reminding doctors, evenly distributing preventive care over a 

period and follow up on results. If the medical record is paper-based then 

alerts such as having a checklist, a separator in the file for prevention care 

and periodically reviewing preventive care delivered may be sufficient. 

3. Cancer preventive care can be initiated by nurses, receptionists, nurse assistants 

for all non-high risk patients, so the process of ordering some tests can be 

initiated by the support staff. It would require some training, to be given by the 

busy family doctor. The physician can follow up on the results with the patient. 

4. Having a counseling team including a dietitian and health educator is 

essential. Physicians at the primary care rarely have time to give good 

counseling regarding cancer prevention. 

5. Facilities such as having a screening mammogram, or setup for pap smear 

collection may vary from practice to practice. Group practices are more able 

to provide such services, however nurses can be trained to do pap smears. 

The detail of the level of evidence for a screening procedure, when to carry out 

a particular procedure and which patient population is high risk for closer follow 

up, are given elsewhere in this manuscript so the emphasis will be on the practical 

aspects of cancer prevention in the clinical setting. 

Colon Cancer 

1. Health education with brochures, videos and group sessions either by self or 

by the health educator about benefits of colon cancer screening, high fiber 

diet and low red meat diet. 

2. Laboratory in clinic or nurses are to teach patient how to do a heme occult test. 

3. Physician to interpret the results and do the flex-sigmoidoscopy if trained and 

has the setup or refer the patient to the gastroenterologist for colonoscopy. 

A well organized setup may help schedule an appointment and help prepare 

patient for colonoscopy. 

4. Aspirin prophylaxis to be considered on a case by case basis. 

5. High risk patients of familial polyposis, inflammatory bowel disease to be 

followed as per guidelines. 

Lung Cancer 

1. Health education with brochures, videos on the hazards of smoking and 

benefits of not smoking and group sessions either by self or by the health 

educator are essential. Smoking is a risk factor for multiple other cancers, 

but it is specifically mentioned here because of being a causative agent. 

2. Having a smoking cessation program in the clinic, with group sessions, 

counseling, nicotine replacement therapy, antidepressants and or vareniciline 

etc should be an essential arsenal of every primary care physician. 

Skin Cancer 

1. Health education with brochures, videos on the hazards of excessive UV 

light (sunlight) exposure, benefits of SPF usage and teaching patients self 

examination of changes in moles (especially those with higher risk; lighter 

skin, multiple moles, elderly (nasolabial folds for basal cell Ca) in group 

sessions either by self or by the health educator. 

2. Physicians may also do periodic skin examination of patients with high risk 

for skin Ca, e.g. those with family history, although there is insufficient 

evidence for this screening procedure. 

Breast Cancer 

1. Health education with brochures, videos on breast cancer, benefits of 

screening mammogram, and teaching patients self examination of breasts, 

in group sessions either by self or by the health educator. 

2. Scheduling screening mammogram periodically for all eligible patients with 

normal risk and those with high risk. For those not in the high risk category 

can be scheduled by the nurse. Patients need to be explained pre-hand about 

the slight discomfort of the mammography procedure in the primary care 

physician office by the nurse. 

3. Physician to break the results to the patient if normal or abnormal and setup 

diagnostic mammogram if needed and counsel patient if results positive. 

4. High risk determination to be carried out by the physician by screening history 

questions exploring family history and advise on genetic marker screening, 

followed by mammography on a schedule as per guidelines. 

Cervical Cancer 

1. Health education with brochures on cervical cancer, benefits of pap smear 

screening and vaccination along with individual counseling either by self 

or by health educator. 

2. Have available in clinic anti-HPV vaccine and setup to deliver it by nursing 

staff who can prepare patients for it and also educate patients on its possible 

side-effects. 

3. Having a setup of conducting pap smear in clinic, either by self or nurse / 

midwife depending upon the size and scope of practice with full explanation 


of procedure to patient. If such a setup is not possible referring patients 

periodically to where the procedure can be carried out. 

4. Interpreting results according to protocol and providing patient support in 

case of positive results. 

Thyroid Cancer 

1. No recommendation on thyroid cancer but it is in the top-ten list of cancers 

among Saudi women, some local screening procedure should be considered 

for research. Ultrasound examination is fast becoming an extension of the 

hands of the primary care physician worldwide, it may be considered as a 

screening tool for research. 

2. Health education with brochures on thyroid cancer, instruction on self neck 

examination, by self or health educator. 

3. Patients with history of radiation to neck or family history of thyroid cancer 

are to be followed closely for periodic examination / ultrasound as per 

recommendations. 

Uterine Cancer 

1. Increase awareness through brochures to peri-menopausal women about 

the risks and symptoms of uterine cancer along with other elements of 

post-menopausal health. 

2. Follow patients with family history of uterine cancer more closely as per 

guidelines. 

Prostate Cancer 

1. Educate patients about prostate cancer through brochures and group sessions 

by self or by health educator. 

2. Consider periodic PSA and DRE for patients in high risk category, such as 

those with darker skin African heritage or family history of prostate cancer 

3. Physicians explain risks and benefits of a positive result and guide patients 

through the decision making process of a positive result. 

Oral Cancer 

1. Health education on the hazards of smoking, tobacco chewing and use of 

pan leaves with betel nuts and tobacco using brochures, waiting room videos 

and group sessions by self or health educator. 

2. Educate patients on detecting oral painless, precancerous lesions by teaching 

them self examination. 

3. Physicians or dentists attached to practice to annually examine the oral 

cavity of high risk patients who smoke or chew tobacco in any form or have 

family history of oral cancer. 

4. Have a smoking cessation / tobacco chewing quitting program in the clinic. 

5. Physician to promptly refer patients in case a precancerous lesion or a painless 

ulcer is detected by oral cavity examination. 

Testicular Cancer 

1. Health education brochures on un-descended testes and self-examination of 

testes should be available in the clinic 

2. Carryout thorough school physical examination of boys to rule out any 

un-descended testes. 

3. Educate parents of boys with un-descended testes on the benefits of surgical 

correction and hazards of un-descended testes (abdominal). Other high 

risk cases such as those with family history are to be followed closely with 

education on self-examination and physician examination. 

Leukemia 

1. No recommendation but primary care physician to make a prompt referral to 

hematologist on incidental discovery of unusually high WBC on CBC done 

for some other purpose or suspicion of leukemia by any other diagnostic 

indicator. 

2. Patients with family history are to be followed up as per recommended 

guidelines. 

Retinoblastoma 

1. No recommendation but primary care physicians must be alert on checking 

a red reflex in infants and toddlers. 

2. Health education material should exist in clinic to alert parents about yellow 

/ white reflex in infants among other alerts for this age. 

3. Primary care physicians should promptly refer patient to ophthalmologist 

for any reflex other than red. . 

Future Role 

1. Oncogene screening of buccal mucosa cells obtained from saliva using 

microchips in the primary care clinic may become a reality of the near 

future, expected to be broadly available within the next 5-10 years, as the 

human genome project progresses to detected newer genes. Customized 

monitoring and prevention counseling for patients possessing oncogenes is 

an immediate outcome with the availability of the genetic testing in family 

doctor’s office. Gene therapy may take longer but prevention counseling to 

alter modifiable risk factors would become the responsibility of the primary 

care physician for which preparations are needed to adjust at various levels 

in healthcare industry. 

2. Use of ultrasound in the primary care setup is fast becoming a useful tool. 

Its application in cancer screening is researchable particularly for cancers 

that are diagnosed late, e.g. pancreatic, ovarian and thyroid etc. 

3. Family physician can play a significant role in tumor registry by having a 

cancer detection program, and a notifiable disease (cancer) reporting system 

for the number screened monthly and detail of those found to be positive. 

Training of Family Physicians 

It is vital that primary care physicians and their staff are trained in early detection of 

cancer, through regular programs and are well supported to deliver these services. 

Reference 

USPSTF Clinical Prevention Guidelines 



ROLE OF PRIMARY CARE PHYSICIAN IN THE PREVENTION AND 

EARLY DETECTION OF CANCER: AN ONCOLOGIST PERSPECTIVE 

Sedky, L. 

Salmania Medical Complex, Bahrain 

Corresponding Author: Prof. Lobna Sedky, MD 

Professor of Clinical Oncology, Cairo University 

Consultant, Medical Oncology, Salmania Medical Complex, Kingdom of Bahrain 

E-mail: lo_sedky@yahoo.com 

Abstract 

Background: It is now recognized that cancer can be preventable, at early 

premalignant phases that provide further opportunities for intervention. Primary 

Care Physicians (PCP) play a pivotal role in cancer control by identifying those 

individuals whose behavior, environment, and/or heredity characteristics place 

them at increased risk for developing cancer. They are in a unique position to 

provide life care, which includes recognizing the need for and recommending 

cancer prevention and early detection when appropriate. 

Material and Method: We reviewed the current status of primary care cancer 

prevention service and science, highlighting barriers against the role of PCPs in 

prevention and early detection of cancer. Furthermore, we explored approaches that 

could help primary care program to achieve its full potential in cancer prevention 

and screening. 

Results: Primary care clinicians face competing demands, conflicting guidelines, 

and lack of systems that support provision of preventive services. The evidencebased 

data on what works for behavioral counseling is especially weak, because 

actual adoption of the guidelines into practice has been slow and inadequate, 

analysis of available literature reported a compliance rate of only 20% to 60%. 

Conclusion: The physicians intellectually support the worth of primary prevention, 

but can not easily insert and/or rationalize it into the culture and expectations of 

clinical practice. Therefore, a persistent public health objective is to develop and 

implement strategies to overcome the barriers that deter provision of primary 

preventive services. 

Introduction 

Until recently, the practice of oncology has focused principally on intervening 

to slow or reverse cancer. Insights from molecular biology and molecular and 

population epidemiology justify interventions within a broadened definition of 

carcinogenesis that includes the continuum of events from the initial genetic or 

epigenetic "hit" to the terminal events. It is now recognized that cancer can be a 

preventable, late stage of the often lengthy disease continuum of carcinogenesis, 

which has reversible early, premalignant phases that provide further opportunities 

for intervention. 

Family physicians can play an invaluable role in caring for patients. Continuity 

of care and multigenerational relationships allow a family physician to guide a 

patient and family through the referral process with a unique knowledge of the 

patient's values, family issues, and communication style. Because of the close 

relationship that primary care physicians often have with their patients, they are 

in a unique position to provide life care, which includes recognizing the need for 

and recommending cancer prevention and early detection when appropriate. 1 

Family physicians play a pivotal role in cancer control by identifying those 

individuals whose behavior, environment, and/or heredity characteristics place them 

at increased risk for developing cancer.2 The busy primary care physician (PCP) 

is often knowledgeable about prospective medicine including cancer prevention 

& early detection, and most feel it is an important part of their practice. However, 

they find difficulty in integrating the necessary health maintenance measures into 

a busy office practice. 

Background 

Primary care plays a central role in promoting cancer prevention to the public but 

has not achieved its full potential in this regard. We will describe the current status 

of primary care cancer prevention service and science then explore approaches that 

could help primary care achieve its full potential in cancer prevention and screening. 

The role of health care practitioner includes: Diagnosing, delivering physical care 

and treatment, educating patients and family members, assessing psychosocial 

strengths and referring for needed services. In addition, offering emotional support, 

assisting in maintaining positive outlook, and advocating for best care.3 

The current status reveals that most people see their primary care clinician several 

times a year and many rely on primary care for screening and behavior advice. 

However, when those who are not up-to-date for cancer screening are asked why? 

the most common reply is, "my doctor didn't recommend it." Recent studies have 

enriched our understanding of the processes by which cancer preventive services 

are provided in primary care. Primary care clinicians face competing demands, 

conflicting guidelines, and lack of systems that support provision of preventive 

services. The evidence-based data on what works for behavioral counseling is 

especially weak. Appropriate models and tools to support delivery of first-rate 

cancer prevention care are being developed. New laboratories for study called 

Practice Based Research Networks are in place but widespread adoption lags. 

Evidence from high quality resources, such as Put Prevention into Practice, 

Cancer Planet, and recommendations of the US Preventive Services Task Force, 

are readily available but seldom consulted or applied.4 

Prevention is defined as the reduction of cancer mortality via reduction in the 

incidence of cancer. This can be accomplished by avoiding a carcinogen or altering 

its metabolism, pursuing lifestyle or dietary practices that modify cancer-causing 

factors or genetic predispositions; and/or medical intervention (chemoprevention) 

to successfully reverse pre-neoplastic changes.5 

Much of the promise for cancer prevention comes from observational epidemiologic 

studies that show associations between modifiable lifestyle factors or environmental 

exposures and specific cancers. Evidence is now emerging from randomized 

controlled trials designed to test whether interventions suggested by the 

epidemiologic studies, as well as leads based on laboratory research, result in 

reduced cancer incidence and mortality.6 

While physicians are key to primary preventive care, their delivery rate is suboptimal. 

The prevailing PCP model was the "one-stop-shop" physician who could 

provide anything from primary to tertiary care, but whose provision was dominated 

by the delivery of immediate diagnoses and treatments, namely secondary care. The 

secondary/tertiary prevention PCP model sustained the expectation of immediacy 

of corrective action, cure, and satisfaction sought by patients and physicians 

alike, and, thereby, de-prioritized primary prevention in practice in favor of the 

immediate benefits of secondary care.7 

Barriers Against The Role of PCPs in Prevention and Early Detection of 

Cancer 

The majority of primary care physicians (PCPs) particularly family physicians, 

concur with the preventive care guidelines and agree that it is their responsibility 

to deliver preventive care services. However, actual adoption of the guidelines 

into practice has been slow and inadequate, studies report a compliance rate of 


only 20% to 60%. Consequently, the lack of preventive care delivery translates to 

lost opportunities to decrease morbidity and mortality via primary and secondary 

prevention. Furthermore, spending time to discuss prevention with a patient was 

perceived by some physicians as not being a prominent element in the role of 

doctor nor an effective use of physician time, hence, the task of prevention could 

be delegated to other members of the medical team.8 

In the case of preventive services guidelines, implementation needs to go beyond 

traditional dissemination and promotion efforts to recognize the added patient and 

clinician barriers that affect preventive care.9 These barriers include: 

1. Clinicians' ambivalence about whether preventive medicine is part of their job 

2. The psychological and practical challenges that patients face in changing 

behaviors 

3. Lack of access to health care or of insurance coverage for preventive services 

offered to some patients. 

4. Competing pressures within the context of shorter office visits and lack of time 

5. The lack of organized systems in most practices to ensure the delivery of 

preventive care recommendation. 

The physicians intellectually support the worth of primary prevention, but can 

not easily insert and/or rationalize it into the culture and expectations of clinical 

practice. Therefore, a persistent public health objective is to develop and implement 

strategies to overcome the barriers that deter provision of primary preventive 

services. A necessary goal of such strategies would be to raise the perceived 

worth and priority of primary prevention within the PCP community, furthermore 

physicians need to expand their self-perceived clinical role to take fuller advantage 

of their unique position to deliver primary preventive care.10 

Implementation Strategies 

The following practice strategies were recommended to help to overcome these barriers:1 

1. Adopt a scientifically based preventive protocol 

PCP should be familiar with rational screening criteria,11 together with 

recommendations of experts and accredited organizations like, Canadian Task 

Force,12 American Cancer Society13, US preventive services task force,14,15 

and American College of Physician.16,17 Meanwhile, they must establish an 

evidence-based health-maintenance protocol appropriate to their situation and 

benefits, with a strong preventive segment that deal with behavioral modifications 

and early diagnosis for the public. This protocol must contain enough flexibility 

to accommodate different cohorts of patients having a variety of risk factors. 

Meanwhile, to be applicable to a wide variety of health care situations including 

public hospitals, clinics, health centers, as well as group and individuals practices. 

2. Development of a Preventive Attitude 

Within the physician who in turn could translate it into educating him or her self 

in preventive and screening procedures. The PCP must learn to communicate with 

their patients in a positive, enthusiastic way to stimulate them to consider being 

subjected to cancer control measures and early detection plan. 

3. Engage the Patient 

Strategies must be developed to have patients as partners to share the responsibility 

for health maintenance. Using patient's handouts, which can stress this responsibility, 

and educate them about the preventive protocol. Another tool is the patient's health 

diaries which contain health maintenance flow charts to be filled by the patient. 

Recently, at higher technical level portable personalized computer smart cards 

which are shaped like credit cards, can contain the patient's medical record data.18 

4. Institutionalize Prevention & Early Detection 

It means committing time and resources to ensure prevention occurs on a regular 

basis for all patients. This strategy is the most important and is the one many 

practices are reluctant to do. Using clear simple guidelines and accurate easy 

methodology for ensuring periodic evaluation feedback. While, it is mandatory 

to identify a coordinator and/or auditor responsible for ensuring integrity of the 

health maintenance tracking system and give feedback about PCP compliance 

with the recommended practice. 

5. Time Management19 

Time saving can be achieved by performing only proven health maintenance 

procedures, as well as keeping an organized record system, but these steps alone 

may not be enough. The incorporation of physician assistants and the use of 

paramedical staff, and nurse practitioners as members of the team can be very 

helpful. 

The Role of Cancer Prevention in Practice 

Cancers occur not as a sudden catastrophic events, but rather as a the result of a 

complex and long-evolving process. Carcinogenesis can take decades to evolve 

completely, providing time and opportunity to intervene to stop or to reverse its 

progress either before the clinical appearance of cancer or at its earliest stages. Due 

to to the continuing burden, public health interventions have focused on prevention 

and early detection to reduce cancer incidence and mortality.20 

Behavior change is a difficult task for both patient and PCP. Physicians believe 

that implementing patient behavior change required changing the patient's 

mindset, yet significant barriers were related to physicians themselves.21 They 

acknowledged their lack of training, knowledge, and skill in behavior change 

process and recommendation conveyance. With participation of both patient and 

PCP about cancer, in addition to the development of a strong preventive attitude, 

the stage will be set for the long term appropriate prevention and early detection 

implementing strategy. For most individuals who are not symptomatic for cancer 

and in good health, unless a physician suggests their participation in a prevention 

study, they are likely to remain unaware of this option. 

As cancer prevention has matured and proved its role in the science and practice of 

oncology. The American Society of Clinical Oncology (ASCO) has strengthened its 

commitment to cancer prevention by establishing its Cancer Prevention Committee 

(CAPC) in 2002. With the major objectives are to improve preventive interventions, 

expand these efforts globally, also to collaborate with FDA on regulatory issues 

involved with preventive drug development.6 Another positive mark, was 

publication of the comprehensive Institute of Medicine report, which offers 

recommendations to increase the rates of adoption, the reach, and the impact of 

evidence-based cancer prevention and early detection interventions.8 

Since cancer can be caused by a variety of different factors and may develop over a 

number of years, therefore some risk factors can be controlled. Choosing the right 

health behaviors and preventing exposure to certain environmental risk factors 

can help prevent the development of cancer. For these reasons, it is important to 

follow national trends to monitor the reduction of these risk factors which focus 

on national trends data from two major groups of risk factors: Behavioral and 

Environmental factors.22 

I. Behavioral Factors 

Scientists estimate that as many as 50–75 percent of cancer deaths are caused by 

human behaviors such as smoking, physical inactivity, and poor dietary choices. 

Major reduction in cancer incidence are possible through improved nutrition, 

physical activity, and avoidance of tobacco products. The latter being the only 



strategy with demonstrated efficacy and broad applicability. Behavioral trends 

that can help to prevent cancer. 

- Tobacco Use:23 

The most consistent finding, over decades of research is the strong association 

between tobacco use and cancers of many sites. Hundreds of epidemiologic 

studies have confirmed this association. Further support comes from the fact that 

lung cancer death rates in the United States have mirrored smoking patterns with 

increases in smoking followed by dramatic increases in lung cancer death rates, 

and more recently decreases in smoking followed by decreases in lung cancer 

death rates in men. 

While smoking causes about 30% of all deaths from cancer. Avoiding both 

smoked and smokeless tobacco use is the single most important step people 

can take to reduce the cancer burden. Taking into consideration, age at smoking 

whether youth or adult smoking, time of quitting, health professional advice and 

recommendations to quit. 

- Diet:24 

It has been estimated that dietary factors are responsible for at least one third of 

cancer mortality. Meanwhile, there is overwhelming evidence that modifiable 

features of lifestyle most notably nutrition dominate in the disease.25 As a general 

rule, epidemiologic studies have suggested association between diet and cancer 

development, but prospective observational or interventional studies have not 

provided strong support. 

PCPs are potentially the most suitable instrument to implement change in diet 

habits as a strategy to prevent cancer. However, several obstacles are encountered, 

such as the fact that most physicians are poorly educated in nutrition, also reactive 

methods of prevention are valued more than proactive modalities. Not surprisingly, 

standard medical textbooks commonly acknowledge data linking diet with cancer 

yet underestimate the role of nutrition in cancer prevention. 

Based on population-based epidemiologic data, health care professionals should 

lead a health advocacy strategy to promote for a healthy weight and encourage 

eating a moderate-fat high fiber diet, with enough fruits and vegetables while 

limiting consumption of red meat which may help to prevent breast and CRC 

cancers.26 While avoiding too much alcohol consumption is also an important 

step in reducing head & neck cancer risk.27 Multivitamin and mineral supplements 

have been advocated for cancer prevention, but the evidence is insufficient. 

It is worth noted that children should be targeted in health promotion campaigns, 

as studies have shown that counseling parents about nutrition can affect children's 

food choices.28 

- Physical Activity:29 

Obesity and physical inactivity cause about 25–30 % of several of the major 

cancers including colon, breast, endometrial, kidney, and esophageal cancers.30 

Obesity is estimated to cause 14 % of cancer deaths in men and 20 % of cancer 

deaths in women.31 

Numerous studies have convincingly demonstrated evidence that undertaking 

and maintaining moderate levels of physical activity rather than hard ones 

confers protective effects against cancer. In addition, they provide a rational 

for incorporating physical activity counseling as part of routine practice in the 

primary care setting. 

Consensus reports have recommended moderate physical activity 30 min a day on 

most days of the week (3 hrs/wk ). Recommendations to health care professionals32 

suggested adoption of a physical activity strategy based on an intensive and 

sustained exercise counseling by visits, calls, and newsletters. Meanwhile to 

ensure effectiveness of such a policy in the community, involving schools through 

physical education classes, after hours recreation, availability of play areas, and 

providing healthy snack foods in school settings. Similarly, promote the availability 

of equipments and trainers for older individuals. Thus, physical activity counseling 

should become component of routine practice in the primary care setting. 

II. Environmental Factors 

Data associated with environmental exposures and their relationship to cancer 

development are reported, such as second hand tobacco smoke (also known as 

environmental tobacco smoke), ionizing radiation, ultraviolet radiation, chemical 

exposures as pesticides & toxins, as well as biological agents. Infections may 

also be associated with cancer development, HPV infection is a necessary event 

for subsequent cancer cervix. Likewise, EBV has been associated with Burkitt’s 

lymphoma and Helicobacter pylori with gastric cancer. 

Prevention can be accomplished by avoiding a carcinogen, or early detection and 

treatment of the precancerous lesion through a sustained follow up of individuals 

known to be at risk. Hence, the role of PCP in the primary care health center.33 

Cancer Risk Assessment and Screening: Facts and Recommendations 

For a growing number of preventive services, available data are sufficiently robust 

to quantify the magnitude of benefits and harms for specific population groups, 

but this precision gives rise to difficult ethical questions about trade-offs.34 If a 

preventive service poses potential benefits and harms, some would recommend that 

avoid making any generic recommendations. Instead uniformly advocate shared 

decision making, in which the clinician reviews the trade-offs with patients and 

helps them decide for themselves based on personal preferences. This approach, 

however, may be impractical and ethically unnecessary except for "close calls" in 

which judgments about whether benefits outweigh harms fluctuate dramatically 

based on personal preferences. Even in those cases, a large proportion of patients 

expects the clinician to give advice.35 

Cancer risk assessment begins in the primary care clinician’s office. Essential 

components of that process include:2 

1. Documentation of personal and family cancer information. 

2. Identification of families at increased risk for cancer. 

3. Modification of cancer screening recommendations according to degree 

of risk. 

4. Referral of high-risk individuals to cancer genetics clinics. 

The risk assessment criteria would be helpful for physicians such as the one 

compiled by Hample et al36 that stratify family history into average, moderate, 

and high genetic risk establishes a threshold for referring patients to cancer 

genetics clinics. Individuals categorized as average risk should follow general 

population guidelines for cancer screening. Moderate risk persons require increased 

surveillance of at-risk organs, whereas high risk groups require cancer genetics 

counseling as well as increased surveillance protocols.37 (Please refer to disease 

specific manuscripts in this issue). 

Whereby encountered patients whose family histories suggest an increased genetic 

risk for cancer without meeting criteria for specific hereditary cancer mutations; 

these individuals may benefit from modified cancer screening protocols and 

other risk reduction measures. Although most cancer genetic risk manifests in 

adulthood, identification of families at increased genetic risk for cancer may be 

lifesaving even in childhood.38 

At all levels of cancer risk, families influence adherence to cancer screening 

and surveillance recommendations. Individuals who test positive for cancerassociated 

mutation may feel less encouraged to express their feeling within 

apparent emotions. While, those who test negative may experience survivor guilt. 

A review of randomized controlled trials involving cancer screening programs 


evealed that providing patients with an individualized risk estimate, increases 

the probability that they will participate in these programs.39 

Genetic Counseling 

For most individuals, a positive family history of cancer confers negligible or 

only slight additional risk. In some patient, however, the family history suggests 

a genetic predisposition to cancer that requires modified screening strategies 

compared with the general population. Rarely, the family history is suggestive of 

a hereditary cancer syndrome that warrants referral to a cancer genetics specialist. 

With the promulgation of guidelines for management of persons at increased 

genetic risk for cancer and the availability of genetic tests to identify those with 

hereditary cancer syndromes family physicians play an increasingly crucial role 

in cancer risk assessment and management.34 

Considerable research effort is now devoted to potential venues for gene therapy 

for individuals with genetic mutations or polymorphisms that put them at high 

risk of cancer. Meanwhile, genetic testing for high-risk individuals with enhanced 

surveillance or prophylactic surgery for those who test positive is already available 

for certain types of cancer including breast and colon cancers.40, 41 

Recommendations 

Towards achieving the full potential of primary care, the jump from the guideline 

page to the community practice has been a long overdue. Currently, the evidence 

is emerging to assure that primary care achieves its potential in cancer prevention 

and early detection. Medical groups, health plans, and policy makers will need to 

support evidence based change processes for practices, that subsequently lead to 

evidence based care processes in the examination room and in the lives of patients. 

Proposed standard operating procedures (SOPs) guidelines of the role of PCP in 

cancer prevention & early detection: 

1. First visit documentation of patient's health profile to identify the individual 

or families at risk for cancer. 

2. Proper generation and maintenance of patient records, and make sure to be 

completed and adequate over time. 

3. Annual visit is scheduled on the patient's birthday. 

4. PCP must be patient, appreciating of patient's fear, communicate in a positive 

enthusiastic way. 

5. PCP should have enough time to explain and discuss the risk factors 

for cancer and the role of physical activity, healthy diet, screening tests, 

chemoprevention, maintenance of health records, and prophylactic surgical 

procedures. 

6. Schedule the patient at risk for the suitable screening workup 

7. Assurance of low risk patients 

8. Referral of high risk cases for genetic counseling 

9. Coordinate referral to curative procedures 

10. Referral to dietitian when indicated 

11. The support staff may include physician assistants, paramedical personnel, 

and nurse practitioner. With supply of educational opportunities as well as 

the time and equipment to address the needs of the patient. 

12. Physician assistants can provide continuity and offer health maintenance 

as part of their job, 

13. Nurses and clerical office personnel can play a role in scheduling, referral 

and reminder calls. 

14. Use of handouts, brochures, CDs about the risk factors and preventive 

measures 

15. Auditing within the team to ensure continuity of a high standard program 

16. Regular refreshing workshops for the PCP and team to maintain update of 

evidence-based procedures and protocols. 

17. To develop continuous medical educational programs (CME) at all levels 

to provide for the educational needs of the PCPs who will carry the burden 

of cancer control in the community. 

18. Cancer-control measures must be coordinated with other health services as 

cardiac, respiratory, metabolic, accidents, and alcohol abuse. 

19. Major items of cancer risk reduction using changing lifestyle measures 

should be part of the routine visit to PCP. The health professional must 

advice the patient verbally, handle flyers, send newsletters, and supply 

referral services as part of the main cancer control strategy. The healthy 

lifestyle recommendations include: 

A. Make healthy food choices 

a. Eat foods high in fiber - try to increase the amount of fiber in your diet 

to between 20 and 30 grams daily. High-fiber foods include whole grains, 

fruits and vegetables. 

b. Limit processed foods, sweets and salt. 

c. Avoid foods high in saturated fats. 

d. Eat 5 of more servings of fruits and vegetables daily. 

e. Choose foods rich in omega-3 fatty acids. 

f. Don’t overeat. Watch portion size and calories. 

g. Limit sweets. 

B. Avoid alcohol consumption. 

C. Maintain a healthy weight. 

D. Engage in regular physical activity, preferably 45 to 60 minutes five 

days per week. 

E. Don’t smoke. 

F. Get regular check-ups and talk to your primary care doctor about regular 

cancer screenings. 

20. Enhance the relationship with policy makers to increase the effectiveness 

of cancer prevention and control activities nationwide 

21. Expand the use of information technology in cancer surveillance, particularly 

in cancer registries. 

22. Conducting research designed to help the cancer community better understand 

the factors that increase cancer risk and identify opportunities to prevent 

cancer. 

Conclusion 

It is estimated that 70% or 80% of cancer could be controlled if preventive measures 

which primarily involve lifestyle modification and early diagnostic procedures 

could be instituted in all our population. 

Clinical preventive medicine for PCPs means offering a comprehensive preventive 

package for each patient. Cancer prevention is an important part of this package. 

Integrating prevention into the fabric of primary care practice is an important 

primary care challenge. Nevertheless, cancer prevention is a major part of this 

effort. PCPs must adopt an evidence based protocol, engage the patient, and 

most importantly commit resources to institutionalize clinical cancer prevention 

and early detection policy. In the past decade, concepts of selective longitudinal 

health maintenance have replaced the previous teaching that all adults should have 

a complete annual physical checkup.66 It is true that PCPs are advisors, yet they 

should act as enforcers as regards the of cancer control. 

If the patient at risk can be convinced that their lives will be longer, better, and 

more productive because of prospective health care, at an affordable price, they 

will be more likely to seek this kind of care and advice from their PCP on a 

continuing basis. 

The PCP's location in the community places him in a unique position to deliver 

the necessary health measures to control cancer within the community. Family 



physicians are therefore now more than ever apart of the multidisciplinary cancer 

care team. 

Delegating the task of primary prevention counseling and education to a team which 

beside the PCP includes as well nutritionists, nurse-educators, health-educators, 

or other trained medical staff could act as a viable alternative 

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Ann Intern Med 1997;127:910-917. 


news from the arab world < 

SAVE THE DATE! 

ASCO Multidisciplinary Cancer Management Course  

(MCMC)   

Hosted by: Gulf International Cancer Center  

Abu Dhabi, UAE.  

February 25 – 27, 2010 

President of the Conference International ASCO Course Director 

Prof. Aly Abdel Razek Prof. Hugo Villar 

  

   

ASCO: American Society of Clinical Oncology    

SEMCO: South & East Mediterranean College of  

Oncology    

  

  

For more information, please contact Prof. Dr. Ahmed Elzawawy   

E‐mail:  worldcooperation@gmail.com OR ahmedelzawawy@hotmail.com 


H E V E N T O G R O U P 

SAVE THE DATE! 

www.winteracademy.net 

ST. MORITZ AND PONTRESINA – APRIL 8-11, 2010 

KEY TOPICS 

Breast cancer: adjuvant therapy 

Colorectal cancer 

Gastrointestinal – non colon: update 

Gynecological session 

Non small cell lung cancer (NLSC) 

Genitourinary cancer 

Focus on new drugs 

Anti-angiogenic agents: 

from biology to clinical trials 

Chemotherapy side effects 

PRESIDENTS 

Prof. Francesco Cognetti, Italy 

Prof. Francesco Di Costanzo, Italy 

Prof. Sami Khatib, Jordan 

INTERNATIONAL BOARD 

Co-Chairman Hamdy Abdel Azim, Egypt 

Omalkhair Abulkhair, KSA 

Said Al Natour, Jordan 

Assem Al Radi, KSA 

Aguilar Enrique Aranda, Spain 

Sandro Barni, Italy 

Corrado Boni, Italy 

Adda Bounedjar, Algeria 

Eric Van Cutsem, Belgium 

Mircea Dediu, Romania 

Hussein Hadi Hashmi, Libya 

Alan Horwich, UK 

Joseph Kattan, Lebanon 

Gurunath Kilara, India 

Claus-Henning Köhne, Germany 

Paris A. Kosmidis, Greece 

Stefan Madajewicz, USA 

Mervat Saud Al-Saleh, Kuwait 

Mohsen Mokhtar, Egypt 

Giovanni Rosti, Italy 

Armando Santoro, Italy 

Michael Untch, Germany 

Yasser Abd El Kader, Egypt 

Shahinaz Bedri, Sudan 

Fawaz Deirawan, Syria 

Khaled Ahmad Al Saleh, Kuwait 

First EURO-ARAB Congress. 


2 ND EDITION


Confirmed Invited speakers: 

Raul Ribeiro (USA) Maarten Egeler (Netherlands) 

Sima Jeha (USA) Stefan J. Friedrichsdorf (USA) 

Monica Metzger (USA) Don Aaronson (Netherlands) 

Sheri Spunt (USA) Mohab Ayas (KSA) 

Matt Krasin (USA) Miguel Abboud (Lebanon) 

Eric Bouffet (Canada) Sara Day (USA) 

Victor Blanchette (Canada) Huda Huijer (Lebanon) 




Conference on Topics in Therapeutic and Diagnostic 

Medical Physics 

Amman, Jordan 

Dead Sea Resort 

April 28th – May 2 nd , 2010 

Sponsored By: 

The American Association of Physicists in Medicine 

(AAPM) 

International Scientific Exchange Program (ISEP) 

Third Arab Radiology Conference (ARC) 

Arab Medical Association Against Cancer (AMAAC) 

Jordan Medical Physics Society (JMPS) 

Program Director 

Dr. Adel Mustafa, AAPM, USA 

Co-Directors 

Dr. Sami Al-Khatib, Secretary General, AMAAC, Jordan 

Dr. Hazem Haboub, Chair of ARC Committee, Jordan 

Dr. Mustafa Al-Majali, President of JMPS, Jordan 

Dr. Samir Khraisat, President of Jordan Radiology Society, Jordan 

Associate Directors 

Dr. Maysoon Al-Taher, AMAAC, Jordan 

Dr. Matthew Al-Ghazi, AAPM, USA 

For more details please contact Dr. Maysoon Al-Taher at 

maysoontahir@hotmail.com 




Amman - Jordan 

July 29-31, 2010 

Conference 

Topics: 

• Breast Tumors • GI/GIST Tumors 

• Lymphoma/Leukemia • Lung Tumors 

• Palliative Care & Oncology Nursing 

Abstracts: 

• Awards will be granted to best 3 abstracts 

• Deadline for submitting abstracts is May 31, 2010 

For more details, you can contact Dr. Jamal Khader at: 

Jkhader@khcc.jo 


notes < 

www.amaac.info Pan Arab Journal of Oncology | vol 3; issue 1 | March 10< 101

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Cervical Cancer Awareness Month 

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objectives & scope of the PAJO < 

The Pan Arab Journal of Oncology (PAJO) is the official Journal of the Arab Medical Association Against Cancer (AMAAC). It is a 

quarterly publication targeting health professionals interested in the oncology field. It is a multidisciplinary peer-reviewed journal that 

publishes articles addressing medical oncology, malignant hematology, surgery, radiotherapy, pediatric oncology, geriatric oncology, 

basic research and the comprehensive management of patients with malignant diseases in addition to international oncology activities, 

congresses & news. 

The journal will be addressed, as a first step, mainly to the professionals in the hematology & oncology field in the Middle East region 

and North Africa. The goal is to share local & regional research activities news and to be updated with international activities. 

We hope, with your support, to achieve our following objectives: 

1. Promote and encourage research activities in the Arab World. 

2. Disseminate & analyze epidemiological local, regional and international data. 

3. Update health professionals with the most recent advances, news & developments in the field of oncology. 

4. Improve the level of scientific publications arising form the Arab World. 

5. Keep health professionals connected and exposed to the activities of different Arab cancer societies. 

6. Share with our immigrant compatriots their activities & feedback in this field. 

7. Involve all health professionals interested in the field of Oncology within the multidisciplinary scope of the Journal. 

8. Encourage post graduates students to submit their research work. 

instructions for authors < 

1. Manuscript Categories 

1.1. Clinical trials 

The Editor-in-Chief and an Associate Editor generally review 

Reports from clinical trials. Selected manuscripts are also reviewed 

by at least two external peer reviewers. Comments offered by 

reviewers are returned to the author(s) for consideration. 

Manuscript acceptance is based on many factors, including the 

importance of the research to the field of oncology & the quality 

of the study. Authors should focus on accuracy, clarity, and brevity 

in their presentation, and should avoid lengthy introductions, 

repetition of data from tables and figures in the text, and unfocused 

discussions. Extended patient demographic data should be included 

in a table, not listed within the text. 

Reports from Clinical trials are limited to 3,000 words of body 

text, excluding the abstract, references, figures, and tables. They 

are limited to six total figures and tables. All abstracts are strictly 

limited to 250 words. Titles are to be descriptive, but succinct. 

Results of clinical studies should be supported by a clear description 

of the study design, conduct, and analysis methods used to obtain 

the results. 

Reports of phase II & III studies should include from the protocol 

a clear definition of the primary end point, the hypothesized value 

of the primary end point that justified the planned sample size, 

and a discussion of possible weaknesses, such as comparison to 

historical controls. 

Phase I studies will be well received if they have interesting clinical 

responses, unusual toxicity that pointed to mechanism of action of 

the agents, and important or novel correlative laboratory studies 

associated with the trials. 

1.2. Review Articles 

All reviews must be clinically oriented, ie, at least half the review 

must describe studies that detail human impact, marker effect on 

prognosis, or clinical trials. 

Review Articles should be prepared in accordance with the Journal’s 

Manuscript Preparation Guidelines, and will be reviewed in the 

same manner as Reports from Clinical Trials. Reviews are limited 

to 4,500 words of body text, excluding the abstract, references, 

figures, and tables. The editors also suggest a limit of 150 references. 

1.3. Editorials / Comments / Controversies 

The Editor-in-Chief may solicit an Editorial to accompany an 

accepted manuscript. Authors who wish to submit unsolicited 

Comments and Controversies should contact the Editor-in-Chief, 

before submission to determine the appropriateness of the topic 

for publication in the Journal. 

Editorials should be no more than four to five pages in length. 

1.4. Articles on Health Economics 

Articles about health economics (cost of disease, cost-effectiveness 

of drugs, etc) are highly encouraged. 

1.5. Case Reports / Correspondence / Special Articles 

Correspondence (letters to the Editor) may be in response to a 

published article, or a short, free-standing piece expressing an 

opinion, describing a unique case, or reporting an observation that 

would not qualify as an Original Report. If the Correspondence is 

in response to a published article, the Editor-in-Chief may choose 

to invite the article’s authors to write a Correspondence reply. 

Correspondence should be no longer than three pages in length. 

Special Articles present reports, news from international, regional 

societies as well as news from our compatriots. 


instructions for the authors < 

2. Manuscript submission procedure 

All manuscripts should be submitted in word and PDF format 

directly to the Editor-in-Chief by email at the following email: 

editorinchief.pajo@yahoo.com. 

The manuscript should adhere to the journal requirements. Upon 

manuscript submission, corresponding authors must provide 

unique e-mail addresses for all contributing authors. Receipt of 

manuscripts will be acknowledged via e-mail. Upon completion of 

editorial review, the corresponding author will receive notification 

of the Editor’s decision, along with the reviewers’ comments, as 

appropriate, via e-mail. 

3. Disclosures of Potential Conflicts of interest 

In compliance with standards established and implemented by 

ASCO’s Conflict of Interest Policy (J Clin Oncol 24:519–521, 

2006), it is the PAJO’s intent, as previously referred, to ensure 

balance, independence, objectivity, and scientific rigor in all of its 

editorial policies related to the Journal through the disclosure of 

financial interests, among other measures. All contributors to the 

Journal are required to disclose financial and other relationships 

with entities that have investment, licensing, or other commercial 

interests in the subject matter under consideration in their 

article. These disclosures should include, but are not limited to, 

relationships with pharmaceutical and biotechnology companies, 

device manufacturers, or other corporations whose products or 

services are related to the subject matter of the submission. 

Disclosures of financial interests or relationships involving the 

authors must be addressed on the Author Disclosure Declaration 

form. The corresponding author may complete the form on behalf 

of other authors, or authors may complete their own forms and 

forward them to the corresponding author. This information will 

be sent to the Editorial Board. Statements regarding financial 

support of the research must be made on the manuscript title page, 

and disclosed on the form. This form is available upon request 

from the Editorial Office. All disclosures will appear in print at 

the end of all published articles. 

The Journal requires all Editors and reviewers to make similar 

disclosures. Reviewers are asked to make disclosures when 

accepting a review. 

4. Manuscript Preparation Guidelines 

Title Page 

The first page of the manuscript must contain the following 

information: (1) title of the report, as succinct as possible; (2) 

author list of no more than 20 names (first name, last name); (3) 

names of the authors’ institutions and an indication of each author’s 

affiliation; (4) acknowledgments of research support; (5) name, 

address, telephone and fax numbers, and e-mail address of the 

corresponding author; (6) running head of no more than 80 characters 

(including spaces); (7) list of where and when the study has been 

presented in part elsewhere, if applicable; and (8) disclaimers, if any. 

Abstract 

Abstracts are limited to 250 words and must appear after the title 

page. Abstracts must be formatted according to the following 

headings: (1) Purpose, (2) Patients and methods (or materials and 

methods, similar heading), (3) Results, and (4) Conclusion. Authors 

may use design instead of Patients and methods in abstracts of 

Review Articles. Comments and Controversies, Editorials and 

Correspondence do not require abstracts. 

Text 

The body of the manuscript should be written as concisely as 

possible and must not exceed the manuscript category word 

limits described herein. All pages of a submission should be 

numbered and double-spaced. Helvetica and Arial at 12pt size 

are the recommended fonts for all text (see Figures section for 

acceptable fonts for figures). The Journal adheres to the style 

guidelines set forth by the International Committee of Medical 

Journal Editors. 

References 

References must be listed and numbered after the body text in the 

order in which they are cited in the text. They should be doublespaced 

and should appear under the heading “REFERENCES.” 

Abbreviations of medical periodicals should conform to those 

used in the latest edition of Index Medicus and on MEDLINE. 

The «List of Journals Indexed in Index Medicus» includes the 

latest abbreviations. Inclusive page numbers must be cited in 

the reference. When a reference is for an abstract or supplement, 

it must be identified as such in parentheses at the end of the 

reference. Abstract and supplement numbers should be provided, 

if applicable. When a reference is a personal communication, 

unpublished data, a manuscript in preparation, or a manuscript 

submitted but not in press, it should be included in parentheses in 

the body of the text, and not cited in the reference list. Published 

manuscripts and manuscripts that have been accepted and are 

pending publication should be cited in the reference list. 

Reference Style 

º Journal article with one, two, or three authors 

1. Dolan ME, Pegg AE: O6-Benzylguanine and its role in 

chemotherapy. Clin Cancer Res 8:837-847, 1997 

º Journal article with more than three authors 

2. Knox S, Hoppe RT, Maloney D, et al: Treatment of cutaneous 

T-cell lymphoma with chimeric anti-CD4 monoclonal antibody. 

Blood 87:893-899, 1996 

º Journal article in press (manuscript has been accepted for 

publication) 

3. Scadden DT, Schenkein DP, Bernstein Z, et al: Combined 

immunotoxin and chemotherapy for AIDS-related non-Hodgkin’s 

lymphoma. Cancer (in press) 

º Supplement 

4. Brusamolino E, Orlandi E, Morra E, et al: Analysis of long-term 


esults and prognostic factors among 138 patients with advanced 

Hodgkin’s disease treated with the alternating MOPP/ABVD 

chemotherapy. Ann Oncol 5:S53-S57, 1994 (suppl 2) 

º Book with a single author 

5. Woodruff R: Symptom Control in Advanced Cancer. Victoria, 

Australia, Asperula Pty Ltd, 1997, pp 65-69 

º Book with multiple authors 

6. Iverson C, Flanagin A, Fontanarosa PB, et al: American Medical 

Association Manual of Style (ed 9). Baltimore, MD, Williams & 

Wilkins, 1998 

º Chapter in a multiauthored book with editors 

7. Seykora JT, Elder DE: Common acquired nevi and dysplastic nevi 

as precursor lesions and risk markers of melanoma, in Kirkwood 

JM (ed): Molecular Diagnosis and Treatment of Melanoma. New 

York, NY, Marcel Dekker, 1998, pp 55-86 

º Abstract 

8. Bardia A, Wang AH, Hartmann LC, et al: Physical activity and 

risk of postmenopausal breast cancer defined by hormone receptor 

status and histology: A large prospective cohort study with 18 years 

of follow up. J Clin Oncol 24:49s, 2006 (suppl; abstr 1002) 

9. Kaplan EH, Jones CM, Berger MS: A phase II, open-label, 

multicenter study of GW572016 in patients with trastuzumab 

refractory metastatic breast cancer. Proc Am Soc Clin Oncol 

22:245, 2003 (abstr 981) 

º Conference/meeting presentation 

10. Dupont E, Riviere M, Latreille J, et al: Neovastat: An 

inhibitor of angiogenesis with anti-cancer activity. Presented at 

the American Association of Cancer Research Special Conference 

on Angiogenesis and Cancer, Orlando, FL, January 24-28, 1998 

º Internet resource 

11. Health Care Financing Administration: Bureau of data 

management and strategy from the 100% MEDPAR inpatient 

hospital fiscal year 1994: All inpatients by diagnosis related groups, 

6/95 update. http://www.hcfa.gov/a1194drg.txt 

º Digital Object Identifier (DOI) 

12. Small EJ, Smith MR, Seaman JJ, et al: Combined analysis of two 

multicenter, randomized, placebo-controlled studies of pamidronate 

disodium for the palliation of bone pain in men with metastatic 

prostate cancer. J Clin Oncol 10.1200/JCO.2003.05.147 

º Government Announcement/Publication 

13. Miller BA, Ries CAG, Hankey BF, et al (eds): Cancer Statistics 

Review: 1973-1989. Bethesda, MD, National Cancer Institute, 

NIH publication No. 92-2789, 1992 

º ASCO Educational Book 

14. Benson AB 3rd: Present and future role of prognostic and 

predictive markers for patients with colorectal cancer. Am Soc 

Clin Oncol Ed Book 187-190, 2006 

Figures 

Figures must be cited in the order they appear in the text using 

Arabic numerals. Figures should be submitted in a seperate 

documen. Figure legends are required for all article types. Figure 

legends must not exceed 55 words per figure and should be written 

below the figure. 

Images may be embedded in word or Power Point files. 

Tables 

Tables must be cited in the order in which they appear in the 

text using Arabic numerals. The table’s legend may include any 

pertinent notes and must include definitions of all abbreviations 

and acronyms that have been used in the table. Tables submitted 

with multiple parts will be renumbered. Tables should be submitted 

in a seperate document. Legends must not exceed 55 words per 

table and should be written above the figure. 

Appendices/Acknowledgments 

Appendices and acknowledgments will appear in the print version 

of the article. 

Language: Appropriate use of the English language is encouraged 

for publication in the Journal. 

5. Post-acceptance Information 

Copyright Form 

Corresponding authors must provide unique e-mail address for each 

contributing author at manuscript submission. Upon acceptance of 

the manuscript, each author will receive an e-mail invitation to sign 

a statement confirming that the manuscript contains no material for 

which publication would violate any copyright or other personal 

or proprietary right of any person or entity. Manuscripts will not 

be published until each author has completed the form. 

Page Proofs 

Corresponding author will receive proofs and must carefully 

review them for data and typesetting errors. Corrections to proofs 

must be returned by e-mail, fax, or mail within 1 week. The 

corresponding author is responsible for collecting and submitting 

all author corrections into a single submission. Publication may 

be delayed if proofs are not returned by the publisher’s deadline. 

The Editor-in-Chief must approve all major alterations, which 

may delay publication of the manuscript. 


subscription to PAJO < 

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In case you are not receiving the PAJO or you would like to 

change your address, kindly to contact us by email to: 

editorinchief.pajo@yahoo.com or by fax to: + 962 65 62 38 53 

and update us with the following information: 

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