title: DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk: a meta-analysis.
abstract: OBJECTIVE
  The X-ray repair cross-complementing group 1 (XRCC1) protein plays a crucial role in base excision repair (BER) pathway by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, a comprehensive meta-analysis of all available studies was performed in this study.
  
  
  METHODS
  PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases have been systematically searched to identify all relevant studies for the period up to February 2013. Data were abstracted independently by two reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed mainly by ethnicity and smoking status.
  
  
  RESULTS
  A total of 26 case-control studies, including 24 studies for R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H polymorphism met the inclusion criteria and were selected. With respect to R399Q polymorphism, significantly decreased bladder cancer risk was found among smokers (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs. GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to R194W and R280H polymorphism, significantly increased bladder cancer risk were observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H, respectively).
  
  
  CONCLUSIONS
  This meta-analysis suggests that the XRCC1 R399Q polymorphism may play a protective role against bladder cancer among smokers. However, the XRCC1 R194W and R280H polymorphisms were both associated with increased bladder cancer risk among Asians. Further studies with larger sample sizes are needed to validate our finds.
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Qiliu
authors.initials: Q
authors.lastname: Peng
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianpeng
authors.initials: J
authors.lastname: You
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.forename: Xianjun
authors.initials: X
authors.lastname: Lao
authors.forename: Huiling
authors.initials: H
authors.lastname: Wu
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zeng
mesh_terms: D044466:Asian People / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012907:Smoking / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human
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