Association between MTHFR Ala222Val (rs1801133) polymorphism and bladder cancer susceptibility: a systematic review and meta-analysis

Folate metabolism is thought to play an important role in carcinogenesis through its involvement in both DNA methylation and nucleotide synthesis. The association between the MTHFR Ala222Val polymorphism and bladder cancer has been widely reported, however, in general the data from published studies with individually low statistical power were controversial and underpowered. Hence, we performed a meta-analysis to investigate the association between bladder cancer and MTHFR Ala222Val in different inheritance models. Fourteen studies including a total of 3,570 bladder cancer cases and 3,926 controls for MTHFR rs1801133 polymorphism were included in the meta-analysis. Data were extracted from these studies and odds ratios with corresponding 95 % confidence intervals (95 % CI) were computed to estimate the strength of the association. Overall, the MTHFR Ala222Val polymorphism was not associated with the development of bladder cancer in all genetic models (Ala/Ala vs. Val/Val—OR = 0.961, 95 % CI = 0.763–1.209; Ala/Ala vs. Ala/Val—OR = 0.918, 95 % CI = 0.795–1.060—Ala/Val vs. Val/Val—OR = 1.022, 95 % CI = 0.852–1.227; dominant model—OR = 0.998, 95 % CI = 0.869–1.145; recessive model—OR = 0.921, 95 % CI = 0.794–1.069; Ala allele vs. Val allele—OR = 0.957, 95 % CI = 0.857–1.067). In the stratified analyses, no significant associations were found among different descent populations and sources of controls. Our meta-analysis suggests that the MTHFR Ala222Val polymorphism not contributes to the development of bladder cancer.