Gene-Smoking Interaction Associations for the ERCC1 Polymorphisms in the Risk of Lung Cancer

Cigarette smoking may induce DNA damage. Lower DNA repair capacities have been associated with higher risk of lung cancer. Excision repair cross-complementing group 1 (ERCC1) is the lead enzyme in the nucleotide excision repair process, and low expression of ERCC1 mRNA levels has been associated with higher risk of cancers. We examined the association between two polymorphisms of ERCC1, 8092C> A (rs3212986) and 19007T> C (codon 118, rs11615), which are associated with altered ERCC1 mRNA stability and mRNA levels, in 1,752 Caucasian lung cancer patients and 1,358 controls. The results were analyzed using logistic regression models, adjusting for relevant covariates. The two polymorphisms were in Hardy-Weinberg disequi-librium and in linkage disequilibrium. There was no overall association between ERCC1 polymorphisms and lung cancer risk, with the adjusted odds ratios (AOR) of 1.26 [95 % confidence interval (95 % CI), 0.81-1.96] for the 8092C> A polymorphism (A/A versus C/C) and 0.93 (95 % CI, 0.67-1.30) for the 19007T> C polymorphism (C/C versus T/T). Stratified analyses revealed that the AORs for the 8092C> A polymorphism (A/A versus C/C) decreased significantly as pack-years increased, with the AOR of 2.11 (95 % CI, 1.03-4.31) in never smokers and 0.50 (95 % CI, 0.25-1.01) in heavy smokers (z56 pack-years), respectively. Consistent results were found when gene-smoking inter-action was incorporated by joint effects and interactions models that considered both discrete and continuous variables for cumulative smoking exposure. The same direc-tion for the gene-smoking interaction was found for the 19007T> C polymorphism, although the interaction was not statistically significant. In conclusion, ERCC1 8092C> A polymorphism may modify the associations between cumu-lative cigarette smoking and lung cancer risk. (Cancer Epidemiol Biomarkers Prev 2005;14(2):491–6