Associations of MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) Polymorphisms with Susceptibility to Bladder Cancer: A Systematic Review and Meta-Analysis

The effects of the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms on bladder cancer risk have been evaluated in some studies. However, the results were conflicting and ambiguous. Therefore, we aimed to perform a comprehensive meta-analysis to investigate the association of these polymorphisms with risk of bladder cancer from all eligible case-control studies. PubMed, Web of science, Scopus, SID, CNKI and SciELO databases were searched to identify all relevant studies published up to 1 January, 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 20 case-control studies including 11 studies with 3463 cases and 3927 controls on MTHFR rs1801133 (677C>T) and 9 studies with 3177 cases and 3502 controls on rs180113 (1298A>C) polymorphism were selected. Pooled data revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not associated with risk bladder cancer in overall. Stratified analysis by ethnicity revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were associated with bladder cancer risk in Asians, but not in Caucasians. There was no publication bias. The current meta-analysis revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not risk factor for development of bladder cancer globally. However, large sample size, well-designed, and population-based studies should be performed to verify the association of the MTHFR polymorphisms with bladder cancer risk.