Carcinogenesis Advance Access originally published online on August 29, 2008
Carcinogenesis 2008 29(11):2147-2152; 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
1 Department of Environmental Health
2 Department of Epidemiology
3 Department of Biostatistics, Harvard School of Public Health, Boston 02115, MA, USA
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 02114, MA, USA
7 Applied Molecular Oncology and Department of Medical Oncology, Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Ontario M5G 2M9, Canada
* To whom correspondence should be addressed. Tel: +1 617 432 6458; Fax: +1 617 432 3441; 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 and 1619 controls). No associations with NSCLC were observed in the main effects analysis for all four 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 with 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 with 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.
Abbreviations: ADC, adenocarcinoma; aOR, adjusted odds ratio; HWE, Hardy–Weinberg equilibrium; LRT, likelihood ratio test; NSCLC, non-small cell lung cancer; OR, odds ratio; SCC, squamous cell carcinoma; SNP, single-nucleotide polymorphisms
Received May 12, 2008; revised August 22, 2008; accepted August 23, 2008.
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