2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

concert with the shared risk of smoking-related genetic and
epigenetic effects. Genome-association studies have identified
several heritable susceptibility or protective loci thought
to affect both COPD and lung cancer development: single
nucleotide polymorphisms on loci 15q25 that regulate cholinergic
nicotine receptors (CHRNA3/5); several haplotypes
involved in the xenobiotic metabolism of tobacco lung carcinogens,
and; genes involved in cell-cycle control, apoptosis,
airway inflammation, and repair. 42,43
Emphysema has recently been found to be associated
with lung cancer, independent of airflow obstruction on
spirometry. Emphysema can be directly quantified on LDCT
with high reproducibility, and commercial software is also
available that can objectively quantify the severity of
smoking-related airway remodeling. 44 In patients with indeterminate
nodules, such characterization could factor into
diagnostic algorithms and may ultimately inform the determination
of screening frequency at the individual patient
level.
Finally, the peripheral blood serves as a repository of
lung cancer-associated cytokines, soluble proteins, and
microRNAs that derive from the tumor microenvironment
and that exhibit molecular signatures similar to those
in tumor tissues. 45,46 Similarly, samples of airway epithelium
obtained through bronchoscopy, sputum expectoration,
or nasal cellular brushings express aberrant methylation
and microRNA patterns observed in lung cancers. 47,48
Authors’ Disclosures of Potential Conflicts of Interest
Author
Christine D. Berg*
Denise R. Aberle*
Douglas E. Wood*
*No relevant relationships to disclose.
Employment or
Leadership
Positions
Consultant or
Advisory Role
1. The National Lung Screening Trial Research Team. Reduced lungcancer
mortality with low-dose computed tomographic screening. N Engl
J Med. 2011;365:395-409.
2. Melamed MR, Flehinger BJ, Zaman MB, et al. Screening for early lung
cancer: Results of the Memorial Sloan-Kettering study in New York. Chest.
1984;86:44-53.
3. Tockman MS, Levin ML, Frost JK, et al. Screening and detection of lung
cancer. In Aisner J (ed). Lung Cancer. New York: Churchill Livingstone,1985;
25-26.
4. Fontana RS, Sanderson DR, Woolner LB, et al. Lung cancer screening:
The Mayo program. J Occup Med. 1986;28:746-750.
5. Kubik A, Parkin DM, Khlat M, et al. Lack of benefit from semi-annual
screening for cancer of the lung: Follow-up report of a randomized controlled
trial on a population of high-risk males in Czechoslovakia. Int J Cancer.
1990;45:26-33.
6. Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality
in the Mayo Lung Project: Impact of extended follow-up. J Natl Cancer Inst.
2000;92:1308-1316.
7. Doria-Rose VP, Marcus PM, Szabo E, et al. Randomized controlled trials
of the efficacy of lung cancer screening by sputum cytology revisited:a combined
mortality analysis from the Johns Hopkins Lung Project and the
Memorial Sloan-Kettering Lung Study. Cancer. 2009;115:5007-5017.
8. Oken MM, Hocking WG, Kvale PA, et al. Screening by chest radiograph
and lung cancer mortality: The Prostate, Lung, Colorectal, and Ovarian
(PLCO) randomized trial. JAMA. 2011;306:1865-1873.
9. Naidich DP, Marshall CH, Gribbin C, et al. Low-dose CT of the lungs:
preliminary observations. Radiology. 1990;175:729-731.
10. The National Lung Screening Trial Research Team. The National
456
If validated, these lung cancer-specific molecular signatures
fromeasily accessible tissues will enable their
translation into clinical practice and will substantially alter
how we define lung-cancer risk and screening in the
future. At 15 of the NLST centers, sponsored by the American
College of Radiology Imaging Network, participants
volunteered to provide serial blood, sputum, and urine
specimens. Lung cancer and other tissue specimens were
collected across the trial and used to construct tissuemicroarrays.
These specimens, when combined with the
voluminous data from the study, may be useful in enhancing
this molecular-signature research. The biospecimens are
available to the research community through a peerreviewed
process. 49
As we begin to more systematically define lung-cancer risk
through combinations of clinical, phenotypic, and molecular
profiling, we will be better positioned to distinguish between
individuals who have lung cancer versus no cancer. Such
discrimination can significantly lower the harms of screening
by reducing unnecessary interventions, minimizing
anxiety, and lowering costs while promoting early diagnosis
and intervention. Finally, the integration of biologic and
imaging-based biomarkers to define risk provides significant
opportunity to stimulate the motivational tension to stop
smoking, which is most important in the prevention of lung
cancer and all smoking-related diseases. The goal is to bring
this epidemic of smoking-related disorders to an end.
Stock
Ownership Honoraria
REFERENCES
Research
Funding
BERG, ABERLE, AND WOOD
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16. Gierada DS, Garg K, Nath H, et al. CT quality assurance in the
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17. Larke FJ, Kruger RL, Cagnon CH, et al. Estimated radiation dose
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18. Berrington de González A, Kim KP, Berg CD. Low-dose lung computed
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