title: Associations of the A66G Methionine Synthase Reductase Polymorphism in Colorectal Cancer: A Systematic Review and Meta-Analysis.
abstract: Inconsistency in the reported associations between the A66G polymorphism in the methionine synthase reductase (MTRR) gene and colorectal cancer (CRC) prompted a meta-analysis, so that we could obtain a more precise estimate. Databases searches of the published literature yielded 20 case-control studies from 17 articles (8,371 cases and 12,574 controls). We calculated pooled odds ratios (ORs) and 95% confidence intervals in three genetic comparisons (A allele, G allele, and A/G genotype). We found no evidence of overall associations between MTRR A66G and CRC risk (OR 0.96-1.05, P = 0.12-0.44). This was materially unchanged when reanalyzed without the Hardy-Weinberg equilibrium (HWE)-deviating studies (OR 0.97-1.06, P = 0.11-0.65). In the A allele comparison, however, outlier treatment generated significant protection (OR 0.91, P = 0.01). Combined removal of the outliers and HWE-deviating studies reflected this summary effect (OR 0.90, P = 0.01) as did the pooled OR from high-quality studies (OR 0.90, P = 0.01). Only the Asian subgroup showed significant (both at P = 0.05) A allele (OR 1.13) and A/G genotype (OR 0.88) associations. In conclusion, post-outlier A allele effects were protective. Our study also suggests ethnic-specific associations with Asian susceptibility and protection in the A allele and A/G genotype comparisons, respectively. Folate status showed no association of this polymorphism with CRC.
authors.affiliation: Center for Research and Development, Angeles University Foundation, Angeles City, Philippines.
authors.forename: Noel
authors.initials: N
authors.lastname: Pabalan
authors.affiliation: College of Allied Medical Professions, Angeles University Foundation, Angeles City, Philippines.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Singian
authors.affiliation: Department of Biological Sciences, Angeles University Foundation, Angeles City, Philippines.
authors.forename: Lani
authors.initials: L
authors.lastname: Tabangay
authors.affiliation: Environmental Monitoring and Reporting Branch, Ontario Ministry of the Environment and Climate Change, Toronto, ON, Canada.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Jarjanazi
authors.affiliation: Genotoxicity Laboratory, Toxicology Division, Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
keywords: A66G; colorectal cancer; methionine synthase reductase; polymorphism