title: Interaction between polymorphisms of DNA repair genes significantly modulated bladder cancer risk.
abstract: DNA repair is a primary defense mechanism against damage caused by exogenous and endogenous sources. We examined the associations between bladder cancer and 7 polymorphisms from 5 genes involved in the maintenance of genetic stability (MMR: MLH1-93G>A; BER: XRCC1--77T>C and Arg399Gln; NER:XPC Lys939Gln and PAT +/-; DSBR:ATM G5557A and XRCC7 G6721T) in 302 incident bladder cancer cases and 311 hospital controls. Genotyping was done using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The homozygous variant of XRCC7 G6721T (Odds Ratio [OR]: 2.36; 95% Confidence Interval [CI]: 1.13-4.92) was associated with increased bladder cancer risk. In an analysis of combined genotypes, the combination of XRCC1Arg399Gln (Gln allele) with XRCC1-77 T/T led to an increase in risk (OR: 1.61; 95% CI: 1.10-2.36). Moreover, when the XPCLys939Gln (Gln allele) (nucleotide excision repair [NER]) was present together with XRCC7 (T allele) (double strand break repair [DSBR]), the bladder cancer risk dramatically increased (OR: 4.42; 95% CI: 1.23-15.87). Our results suggest that there are multigenic variations in the DNA repair pathway involved in bladder cancer susceptibility, despite the existence of ethnic group differences.
authors.affiliation: Department of Cell Biology, Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhi
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Wei
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D004260:DNA Repair / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C086984:XPC protein, human; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D000070957:MutL Protein Homolog 1