title: APEX nuclease (multifunctional DNA repair enzyme) 1 gene Asp148Glu polymorphism and cancer risk: a meta-analysis involving 58 articles and 48903 participants.
abstract: BACKGROUND
  Polymorphisms in the APEX nuclease (multifunctional DNA repair enzyme) 1 gene (APEX1) may be involved in the carcinogenesis by affecting DNA repair. We aimed to summarize available data on the association of the APEX1 Asp148Glu (rs1130409) polymorphism with risk of multiple types of cancer via a meta-analysis.
  
  
  RESULTS
  In total, 58 qualified articles including 22,398 cancer patients and 26,505 controls were analyzed, and the data were extracted independently by two investigators. Analyses of the full data set indicated a marginally significant association of the APEX1 Asp148Glu polymorphism with cancer risk under allelic (odds ratio (OR)=1.05; 95% confidence interval (95% CI): 0.99-1.11; P=0.071), dominant (OR=1.09; 95% CI: 1.01-1.17; P=0.028), and heterozygous genotypic (OR=1.08; 95% CI: 1.01-1.16; P=0.026) models, with significant heterogeneity and publication bias. In subgroup analyses by cancer type, with a Bonferroni corrected alpha of 0.05/6, significant association was observed for gastric cancer under both dominant (OR=1.74; 95% CI: 1.2-2.51; P=0.003) and heterozygous genotypic (OR=1.66; 95% CI: 1.2-2.31; P=0.002) models. In subgroup analysis by ethnicity, risk estimates were augmented in Caucasians, especially under dominant (OR=1.11; 95% CI: 1.0-1.24; P=0.049) and heterozygous genotypic (OR=1.11; 95% CI: 0.99-1.24; P=0.063) models. By study design, there were no significant differences between population-based and hospital-based studies. In subgroup analysis by sample size, risk estimates were remarkably overestimated in small studies, and no significance was reached in large studies except under the heterozygous genotypic model (OR=1.23; 95% CI: 1.06-1.43; P=0.006, significant at a Bonferroni corrected alpha of 0.05/2). By quality score, the risk estimates, albeit nonsignificant, were higher in low-quality studies than in high-quality studies. Further meta-regression analyses failed to identify any contributory confounders for the associated risk estimates.
  
  
  CONCLUSIONS
  Our findings suggest that APEX1 Asp148Glu polymorphism might be a genetic risk factor for the development of gastric cancer. Further investigations on large populations are warranted.
authors.affiliation: Department of Pathology, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China ; Fujian Provincial Key Laboratory of Translational Center Medicine, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Pathology, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China ; Fujian Provincial Key Laboratory of Translational Center Medicine, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China.
authors.forename: Xiandong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pathology, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China ; Fujian Provincial Key Laboratory of Translational Center Medicine, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China.
authors.forename: Hejun
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China ; Fujian Provincial Key Laboratory of Translational Center Medicine, Fujian Provincial Tumor Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian province, China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wenquan
authors.initials: W
authors.lastname: Niu
mesh_terms: D019943:Amino Acid Substitution; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase