2009 Vienna - European Society of Human Genetics

Cancer genetics
P06.139
the role of estrogen receptor alpha 5’ UtR methylation in
pathogenesis of iranian patients with breast cancer
H. Loghmani Khouzani 1,2 , M. H. Karbasian 3 , M. Noruzinia 1,2 , M. J. Rasaee 1 , P.
Fatehmanesh 2 , M. Keyhanee 2 ;
1 Tarbiat Modares University, Tehran, Islamic Republic of Iran, 2 Sarem Research
Center (SARC), Tehran, Islamic Republic of Iran, 3 Day hospital, Tehran, Islamic
Republic of Iran.
Introduction: Methylation pattern in promoter region of many genes
are proved to be modified in cancers. 5’ UTR of estrogen receptor
alpha has been shown to be differentially methylated in some patients
with breast cancer and is believed to be a marker in early diagnosis,
prognosis and treatment. On the other hand, known genetic causes of
breast cancer like BRCA genes couldn’t explain early breast cancer in
Iranian patients with breast and/or ovarian cancers. Our objective was
to explore the role of epigenetic modification in ERα 5’ flanking region
in Iranian patients with breast cancer.
Materials and methods: Methylation Specific PCR on sodium bisulfate
treated DNAs of peripheral blood and tissue samples from 35 patients
with breast cancer were performed. Primers were selected to be specific
for 2 known CpG islands in 5’UTR of ERα either for methylated or
unmethylated status.
Results: We found that in 53.85% of primary breast cancers CpG island
I is methylated and in 80.77% CpG island II is methylated. The
methylation status of these CpG islands in blood was 100% and
87.88% respectively.
Discussion: We find a trend to methylation in breast tissue of Iranian
patients with breast cancer. Our result show a methylation tendency in
breast tumors compared to those reported in the literature. We found
a high rate of methylation in peripheral blood which is in concordance
to other studies. Our results are in concordance to the studies which
showed a role of ER alpha methylation in pathogenesis of breast cancer.
P06.140
Association of COX-2 -765G→C promoter variants with colon
cancer from iran
S. Basatvat1 , F. Biramijamal1 , A. Hossein-Nezhad1 , K. Shamimi2 , G. Irvanloo3 ,
M. Soltani1 , K. Akbari1 ;
1 2 NIGEB, Tehran, Islamic Republic of Iran, Dept. of Surgery, Tehran University
of Medical Sciences, Tehran, Islamic Republic of Iran, 3Cancer Institute, Tehran
University of Medical Sciences, Tehran, Islamic Republic of Iran.
Cyclooxygenases-2 enzyme (COX-2) converts arachidonic acid to
prostaglandins.The COX2 gene plays an important role in inflammation
and carcinogenesis process. Previous studies indicated that polymorphism
of this gene is associated with inflammatory diseases and
several types of cancer. It has been shown that the COX-2 -765G > C
promoter polymorphism have lower promoter activity and decreased
COX-2 expression. In addition, genetic polymorphisms of the COX-
2 gene could alter the response to Nonsteroidal anti-inflammatory
drugs (NSAIDs). The aim of this study is to determine the association
of the COX2 gene polymorphism with development of colon cancer.
Colorectal cancer is the third cause of the cancer-related death in the
world. To understand the etiology of colon cancer in Iran, we initiated
a study to investigate genetic polymorphism (-765G→C promoter variants)
of Cyclooxygenase-2 (COX-2) among Iranian colon cancer patients,
the COX-2 -765G > C promoter genotypes were determined by
polymerase chain reaction-restriction fragment length polymorphisms
(PCR-RFLP) analysis in 16 Iranian colon cancer patients and 193
healthy individuals. The frequency of C allele was demonstrated more
among colon cancer patients. Range of C allele frequency was 22.5%
in healthy individuals to 50% in patients . Significance difference in
COX-2 allele distribution was observed between patients and healthy
individuals (P value