Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer.
Excision repair cross-complementing group 2 (ERCC2), a major DNA repair protein, is involved in nucleotide excision repair and basal transcription. The ERCC2 polymorphisms have been associated with altered DNA repair capacity. We investigated two ERCC2 polymorphisms, Asp312Asn and Lys751Gln, in 1092 Caucasian lung cancer patients and 1240 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. The overall adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.47 (95% CI, 1.1-2.0) for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp) and 1.06 (95% CI, 0.8-1.4) for the Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). Gene-smoking interaction analyses revealed that the adjusted ORs for each of the two polymorphisms decreased significantly as pack-years increased. When comparing individuals with Asn/Asn + Gln/Gln versus individuals with Asp/Asp + Lys/Lys, the fitted ORs (95% CIs) were 2.56 (95% CI, 1.3-5.0) in nonsmokers and 0.69 (95% CI, 0.4-1.2) in heavy smokers (80 pack-years; P < 0.01 for the interaction term). Consistent and robust results were found when models incorporated different definitions of cumulative cigarette smoking. A stronger gene-smoking interaction was observed for the Asp312Asn polymorphism than for the Lys751Gln polymorphism. In conclusion, cumulative cigarette smoking modifies the associations between ERCC2 polymorphisms and lung cancer risk.
Zhou
Wei
W
Occupational Health Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Liu
Geoffrey
G
Miller
David P
DP
Thurston
Sally W
SW
Xu
Li Lian
LL
Wain
John C
JC
Lynch
Thomas J
TJ
Su
Li
L
Christiani
David C
DC
D000328:Adult; D000368:Aged; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012306:Risk; D012907:Smoking / Q000009:adverse effects*; D014157:Transcription Factors; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human