A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer.
Cigarette smoking is the major cause of bladder cancer. Constituents in tobacco smoke can induce oxidative DNA damage requiring base excision repair. The Arg399Gln polymorphism in the DNA base excision repair gene XRCC1 is associated with several phenotypic markers of reduced DNA repair capacity. Results from several epidemiologic studies suggest that the Arg399Gln polymorphism may influence susceptibility to several cancers including bladder cancer; however, data from large population-based studies are lacking. In a population-based case-control study from New Hampshire, we observed a reduced risk among those homozygous for the Arg399Gln XRCC1 variant polymorphism compared with those with one or two wild-type alleles (odds ratio 0.6, 95% confidence interval 0.4-1.0). There was no indication of a gene-environment interaction between cigarette smoking and the variant genotype. Our data are consistent with a potential role of the XRCC1 Arg399Gln polymorphism in bladder cancer susceptibility and further suggest that there may be DNA lesions important in bladder carcinogenesis, repaired by the base excision repair mechanism, that are not directly associated with tobacco smoking.
Department of Genetics and Complex Diseases, Harvard School of Public Health, Building 1, Room 607, 665 Huntington Avenue, Boston, MA 02115, USA. kelsey@hsph.harvard.edu
Karl T
KT
Kelsey
Sunyeong
S
Park
Heather H
HH
Nelson
Margaret R
MR
Karagas
D017677:Age Distribution; D001483:Base Sequence; D016022:Case-Control Studies; D016001:Confidence Intervals; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000473:pathology*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology
D004268:DNA-Binding Proteins