title: Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy.
abstract: Tobacco smoking and occupational exposures are the main known risk factors for bladder cancer, causing direct and indirect damage to DNA. Repair of DNA damage is under genetic control, and DNA repair genes may play a key role in maintaining genome integrity and preventing cancer development. Polymorphisms in DNA repair genes resulting in variation of DNA repair efficiency may therefore be associated with bladder cancer risk. A hospital-based case-control study was conducted in Brescia, Italy, to assess the relationship between polymorphisms in DNA repair genes XRCC1 (Arg(399)Gln), XRCC3 (Thr(241)Met), and XPD (Lys(751)Gln) and bladder cancer risk. A total of 201 male incident bladder cancer cases and 214 male controls with urological nonneoplastic diseases were recruited and frequency-matched on age, period, and hospital of recruitment. Detailed information was collected using a semistructured questionnaire on demographic, dietary, environmental, and occupational factors. Genotypes were determined by PCR-RFLP analysis. The XRCC3 codon 241 variant genotype exhibited a protective effect against bladder cancer [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42-0.93], which was prominent among heavy smokers (OR, 0.49; 95% CI, 0.28-0.88) but not among never and light smokers. No overall impact of the XRCC1 codon 399 polymorphism was found (OR, 0.86; 95% CI, 0.59-1.28), but a protective influence of the homozygous variant was suggested among heavy smokers (OR, 0.38; 95% CI, 0.14-1.02). XPD polymorphisms did not show an association with bladder cancer (OR, 0.92; 95% CI, 0.62-1.37). There was no statistical evidence of an interaction between these three genetic polymorphisms and either tobacco smoking or occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines. The XRCC3 codon 241 polymorphism had an overall protective effect against bladder cancer that was most apparent among heavy smokers. Similarly, the XRCC1 codon 399 polymorphism also had a protective effect on bladder cancer among heavy smokers. The XPD polymorphism was not, however, associated with bladder cancer risk.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Christian
authors.initials: C
authors.lastname: Malaveille
authors.forename: Francesco
authors.initials: F
authors.lastname: Donato
authors.forename: Donatella
authors.initials: D
authors.lastname: Placidi
authors.forename: Angela
authors.initials: A
authors.lastname: Carta
authors.forename: Agnes
authors.initials: A
authors.lastname: Hautefeuille
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Stefano
authors.initials: S
authors.lastname: Porru
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000494:pharmacology; D004781:Environmental Exposure; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000494:pharmacology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014157:Transcription Factors; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein
chemical_list: D004268:DNA-Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human