APEX Nuclease (Multifunctional DNA Repair Enzyme) 1 Gene Asp148Glu Polymorphism and Cancer Risk: A Meta-Analysis Involving 58 Articles and 48903 Participants

• Published in: PloS one Vol. 8; no. 12; p. e83527
• Main Authors: Hu, Dan, Lin, Xiandong, Zhang, Hejun, Zheng, Xiongwei, Niu, Wenquan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.12.2013; Public Library of Science (PLoS)
• Subjects: Amino Acid Substitution; Bias; Bladder cancer; Cancer; Cancer genetics; Carcinogenesis; Carcinogens; Colorectal cancer; Confidence intervals; Data processing; Deoxyribonucleic acid; Development and progression; DNA; DNA repair; DNA-(Apurinic or Apyrimidinic Site) Lyase - genetics; Enzymes; Estimates; Female; Gastric cancer; Gene polymorphism; Genes; Genetic aspects; Genetic polymorphisms; Genomics; Genotype & phenotype; Health aspects; Health risks; Heterogeneity; Humans; Laboratories; Lung cancer; Male; Medical ethics; Medical prognosis; Medicine; Meta-analysis; Minority & ethnic groups; Mutation; Mutation, Missense; Neoplasm Proteins - genetics; Nuclease; Pathology; Polymorphism; Polymorphism, Genetic; Population; Population studies; Prostate cancer; Regression analysis; Repair; Risk analysis; Risk Factors; Statistical analysis; Stomach cancer; Stomach Neoplasms - genetics; Studies; Teaching hospitals; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083527

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. 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. 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.