title: Two DNA repair gene polymorphisms on the risk of gastrointestinal cancers: a meta-analysis.
abstract: PARP-1 and MGMT play an important role in the DNA repair system and therefore have been implicated in human carcinogenesis. However, the association between the most studied PARP-1 rs1136410: T > C and MGMT rs12917: C > T polymorphism and risk of gastrointestinal (GI) cancers was reported with inconclusive results. Accordingly, a meta-analysis of 23 published case-control studies was conducted to assess the strength of association using crude odds ratios (ORs) with 95% confidence intervals (CIs). Overall, the C allele of PARP-1 rs1136410: T > C polymorphism was significantly associated with increased susceptibility of GI cancers (homozygote comparison: OR = 1.43, 95% CI 1.14-1.81; heterozygote comparison: OR = 1.18, 95% CI 1.07-1.29; dominant model: OR = 1.23, 95% CI 1.12-1.35; recessive model: OR = 1.30, 95% CI 1.04-1.62; allelic comparison: OR = 1.19, 95% CI 1.07-1.32). In the subgroup analysis, still obvious associations were found in the Asian population, gastric cancer, and high-quality studies. For MGMT rs12917: C > T polymorphism, no obvious associations were found for all genetic models overall. However, in the subgroup analysis, we found that the T allele was significantly associated with reduced colorectal cancer risk for heterozygote (OR = 0.83, 95% CI 0.70-0.97) and dominant model (OR = 0.84, 95% CI 0.72-0.98). In conclusion, this meta-analysis suggests that the PARP-1 rs1136410: T > C polymorphism is a susceptibility factor for GI cancers, but the variant allele of MGMT rs12917: C > T polymorphism appears to be a protective factor for colorectal cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.
authors.affiliation: Tumor Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiangquan
authors.initials: X
authors.lastname: Kong
authors.forename: Yamei
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jianxu
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D015254:DNA Modification Methylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics*; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D045643:DNA Repair Enzymes