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Carcinogenesis Advance Access published online on August 29, 2008
Carcinogenesis, doi:10.1093/carcin/bgn205
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Published by Oxford University Press 2008.

Apoptosis gene polymorphisms, age, smoking and the risk of non-small cell lung cancer

Monica Ter-Minassian1, Rihong Zhai1, Kofi Asomaning1, Li Su1, Wei Zhou1, Geoffrey Liu4,7, Rebecca Suk Heist1,4, Thomas J. Lynch5, John C. Wain6, Xihong Lin3, Immaculata DeVivo2 and David C. Christiani1,2,5

1 Department of Environmental Health
2 Department of Epidemiology
3 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts
4 Massachusetts General Hospital Cancer Center
5 Pulmonary and Critical Care Unit
6 Thoracic Surgery Unit, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts
7 Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario, Canada

Email: mtermina{at}hsph.harvard.edu

Apoptosis is important for targeting cancer cells for destruction. Various single nucleotide polymorphisms (SNPs) in apoptotic genes have been associated with increased risks in lung cancer, particularly FAS -1377 G>A (rs2234767), FASLG -844 C>T (rs763110), IL1B +3954 C>T Phe105Phe (rs1143634) and BAT3 Ser625Pro (rs1052486). We studied the association of these SNPs with non-small cell lung cancer (NSCLC) in a large case-control study (N = 4263: 2644 cases, 1619 controls). No associations with NSCLC were observed in the main effects analysis for all 4 SNPs, adjusting for age, gender, smoking status, pack years, and years since smoking cessation. In subjects under age 60, for FASLG -844 C>T polymorphism, CT compared to the CC genotype, was significantly associated with increased risk of NSCLC, adjusted odds ratio (aOR) = 1.58 (1.22, 2.05), p = 0.0006 and TT aOR = 1.45 (1.01, 2.04), p = 0.04. In contrast, for those over age 60, the CT aOR = 0.91 (0.73, 1.13), p = 0.37; and TT aOR = 0.86 (0.64, 1.16) p = 0.32. The p-value for the age-genotype interaction was 0.004. For the IL1B +3954 C>T polymorphism, compared to the CC genotype, TT showed significant associations in former smokers and in men but tests of interaction were not significant (psmoking=0.24), (pgender = 0.17). No interactions were observed for FAS -1377 G>A and BAT3 Ser625Pro polymorphisms. Our findings indicate that age and smoking may modify the association of the FASLG -844 and IL1B + 3954 SNPs with the risk of NSCLC.

Received May 12, 2008; revised August 22, 2008; accepted August 23, 2008.


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