title: Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses.
abstract: Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19-2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65-1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28-3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43-4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21-1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95-1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral.
authors.affiliation: Department of Urology, King George Medical University, Lucknow, India.
authors.forename: Monica
authors.initials: M
authors.lastname: Sankhwar
authors.affiliation: Department of Urology, King George Medical University, Lucknow, India.
authors.forename: Satya Narayan
authors.initials: SN
authors.lastname: Sankhwar
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Bansal
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000503:physiopathology; D064424:Tobacco Use / Q000503:physiopathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human