title: Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk.
abstract: APE1 (apurinic/apyrimidinic endonuclease 1) and XRCC1 (X-ray cross-complementing group 1) are DNA repair proteins that play important roles in the base excision repair (BER) pathway. Polymorphisms in their encoding genes are associated with altered DNA repair capacity and thus may impact on cancer risk. In the present case-control study with 178 Japanese incident lung cancer cases and 449 age- and sex-matched controls, we investigated the gene-environment interaction among APE1 Asp148Glu, XRCC1 Arg399Gln and smoking habit in lung cancer risk. The results were analyzed by using conditional logistic regression models, adjusted for age, sex and smoking status. The adjusted odds ratio for the current smokers with APE1 148Asp/Asp, Asp/Glu and Glu/Glu genotype as compared with the never smokers with the Asp/Asp genotype were 3.01 (95% CI 1.39-6.51, P = 0.005), 2.73 (95% CI 1.29-5.77, P = 0.008) and 7.33 (95% CI 2.93-18.3, P < 0.001), respectively. The gene-environment interaction between current smoking and APE1 148Glu/Glu genotype was statistically significant (OR 3.59, 95% CI 1.28-10.1, P = 0.015). When APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were evaluated together, the adjusted odds ratios for the current smokers with 0-1, 2 and 3-4 of APE1 148Glu or XRCC1 399Gln alleles as compared with never smokers with the 0 of these alleles were 2.96 (95% CI 1.57-5.58, P = 0.001), 3.86 (95% CI 1.85-8.05, P < 0.001) and 6.01 (95% CI 2.25-16.1, P < 0.001), respectively. The gene-environment interaction between current smoking and three or more APE1 148Glu or XRCC1 399Gln alleles was statistically significant (OR 2.44, 95% CI 1.00-9.22, P = 0.049). The OR for the gene-environment interaction of Glu/Glu genotype of APE1 codon 148 with heavy smoking was 1.04 (95% CI 0.38-2.90, P = 0.936) and that with light smoking was 2.67 (95% CI 1.00-7.68, P = 0.049). These results suggest that APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms might modify the risk of lung cancer attributable to cigarette smoking exposure.
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya Aichi, Japan. hidemi@aichi-cc.jp
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sugiura
authors.forename: Toshiko
authors.initials: T
authors.lastname: Saito
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yasue
authors.forename: Kyoung-Mu
authors.initials: KM
authors.lastname: Lee
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sato
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001120:Arginine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D003062:Codon; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D012307:Risk Factors; D012907:Smoking; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D001120:Arginine; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase