title: Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk.
abstract: X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene whose polymorphisms appear to influence the risk of lung cancer. We explored the influence of antioxidants on the association between the codon 194 arganine to tryptophan substitution polymorphism of XRCC1 and lung cancer risk. In a case-control study nested within a cohort of tin miners the cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Individuals with the variant Arg194Trp allele seemed to be at lower risk for lung cancer (odds ratio (OR): 0.7, 95% confidence interval (95%CL): 0.4-1.2). Furthermore, high serum alpha-tocopherol (OR: 0.4, 95%CL: 0.2-0.9) and retinol (OR: 0.4, 95%CL: 0.2-0.9) levels were associated with significantly reduced risk of lung cancer among individuals with the Arg194Trp variant allele, but not among individuals with the wild-type genotype. In addition, the Arg194Trp variant reduced the risk of lung cancer associated with increased serum carotenoids compared to those with the homozygous wild-type allele. Our results show that Arg194Trp XRCC1 variant modifies the association between serum antioxidants and lung cancer risk.
authors.affiliation: Center for Structural Genomics, 3900 NCTR Drive, NCTR, FDA, Jefferson, AR-72079, USA. Lratnasinghe@NCTR.FDA.GOV
authors.forename: D Luke
authors.initials: DL
authors.lastname: Ratnasinghe
authors.forename: Shu-Xiang
authors.initials: SX
authors.lastname: Yao
authors.forename: Michele
authors.initials: M
authors.lastname: Forman
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.forename: Mark R
authors.initials: MR
authors.lastname: Andersen
authors.forename: Carol A
authors.initials: CA
authors.lastname: Giffen
authors.forename: Yener
authors.initials: Y
authors.lastname: Erozan
authors.forename: Melvyn S
authors.initials: MS
authors.lastname: Tockman
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000975:Antioxidants / Q000378:metabolism*; D001120:Arginine / Q000235:genetics; D003043:Cocarcinogenesis; D003062:Codon; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008906:Mining; D009790:Occupations; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014364:Tryptophan / Q000235:genetics; D014801:Vitamin A / Q000097:blood; D000076105:X-ray Repair Cross Complementing Protein 1; D024502:alpha-Tocopherol / Q000097:blood; D019207:beta Carotene / Q000097:blood
chemical_list: D000975:Antioxidants; D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D019207:beta Carotene; D014801:Vitamin A; D014364:Tryptophan; D001120:Arginine; D024502:alpha-Tocopherol