Methionine synthase reductase (MTRR) gene is involved in
tumorigenesis by regulating DNA methylation through activation of
methionine synthase (MTR). MTRR is polymorphic at
nucleotide 66 (A-to-G) and the resulting variant
enzyme has a lower affinity for MTR. The reported associations of MTRR A66G polymorphism with
cancer risk are contradictory. Therefore, we performed a meta-analysis to better assess the associations, including 18,661 cases and 27,678 controls from 35 studies. Crude
ORs with 95% CIs were used to assess the strength of association between the MTRR A66G polymorphism and
cancer risk. The pooled
ORs were performed for homozygote model (GG vs. AA), heterozygote model (GG vs. GA), recessive genetic model (GG vs. GA + AA), and dominant genetic model (GG + GA vs. AA), respectively. Overall, results indicated that the G allele and GG variant genotypes were associated with a significantly increased
cancer risk (G vs. A: OR, 1.039; 95% CI, 1.009-1.078; homozygote model: OR, 1.094; 95% CI, 1.006-1.191). In subgroup analysis by ethnicity, significant increased risks were found among Asians with G allele (G vs. A: OR, 1.063; 95% CI, 1.011-1.119; homozygote model: OR, 1.189; 95% CI, 1.055-1.341; recessive model: OR, 1.197; 95% CI, 1.068-1.341). For stratification analysis, the
cancer types with fewer than three studies were categorized into "other
cancers", and the results indicated that there was a significant elevated
cancer risk in "other
cancers" in all genetic models, not in
colorectal cancer,
lymphoid leukemia or
breast cancer. In summary, our study suggests that the MTRR A66G polymorphism is a potential
biomarker for
cancer risk.