title: The polyAT, intronic IVS11-6 and Lys939Gln XPC polymorphisms are not associated with transitional cell carcinoma of the bladder.
abstract: Chemical carcinogens from cigarette smoking and occupational exposure are risk factors for bladder transitional cell carcinoma (TCC). The Xeroderma Pigmentosum Group C (XPC) gene is essential for repair of bulky adducts from carcinogens. The Xeroderma Pigmentosum Group C gene polymorphisms may alter DNA repair capacity (DRC), thus giving rise to genetic predisposition to bladder cancer. Recent studies have demonstrated linkage disequilibrium between three polymorphisms in the XPC gene (polyAT, IVS11-6 and Lys939Gln) and these have been shown to influence the DRC, as well as to be associated with bladder cancer risk. We analysed all three XPC polymorphisms in 547 bladder TCC patients and 579 cancer-free controls to investigate the association between these polymorphisms and bladder cancer susceptibility, and we also attempted to assess gene-environmental interactions. We confirmed strong linkage disequilibrium among the polymorphisms (Lewontin's D' > 0.99). Using logistic regression adjusting for smoking, occupational and family history, neither the heterozygote nor the homozygote variants of these polymorphisms were associated with increased bladder cancer risk (adjusted odds ratio [95% confidence interval] for heterozygote 0.82 [0.63-1.07], 0.82 [0.63-1.08] and 0.83 [0.63-1.08] for PolyAT, IVS11-6 and Lys939Gln, respectively and homozygote variant, 0.98 [0.68-1.42], 0.99 [0.69-1.43] and 1.01 [0.70-1.46]). Moreover, we did not find any significant interaction between these XPC polymorphisms and environmental exposure to cigarette smoking and occupational carcinogens.
authors.affiliation: Molecular Radiobiology Group, Cancer Research UK Clinical Centre in Leeds, St James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Sak
authors.forename: J H
authors.initials: JH
authors.lastname: Barrett
authors.forename: A B
authors.initials: AB
authors.lastname: Paul
authors.forename: D T
authors.initials: DT
authors.lastname: Bishop
authors.forename: A E
authors.initials: AE
authors.lastname: Kiltie
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human