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Quantitative assessment of the association between MHTFR C677T (rs1801133, Ala222Val) polymorphism and susceptibility to bladder cancer

Wei Xu1, Haifeng Zhang2, Fa Wang1 and Honghui Wang1*

Author affiliations

1 Department of Interventional Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China

2 Department of Urinary Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China

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Citation and License

Diagnostic Pathology 2013, 8:95  doi:10.1186/1746-1596-8-95

Published: 17 June 2013



The association between Methylenetetrahydrofolate reductase (MTHFR) Ala222Val (rs1801133) has been implicated to alter the risk of bladder cancer, but the results are controversial.


A comprehensive databases of Pubmed, Embase, Web of Science, and the Chinese Biomedical Database (CBM) were searched for case–control studies investigating the association between MTHFR Ala222Val polymorphism and bladder cancer susceptibility. Odds ratios (OR) and 95% confidence intervals (95%CI) were used to assess this possible association. A χ2-based Q-test was used to examine the heterogeneity assumption. Begg’s and Egger’s test were used to examine the potential publication bias. The leave-one-out sensitivity analysis was conducted to determine whether our assumptions or decisions have a major effect on the results of the review. Statistical analysis was performed with the software program Stata 12.0.


A total of 15 independent studies were identified, including 3,570 cases and 3,926 controls. Our analysis suggested that Ala222Val was not associated with bladder cancer risk in overall population under additive model (OR=0.96, 95%CI=0.76-1.21, P=0.731), dominant model (OR=1.00, 95%CI=0.87-1.15, P=0.975), recessive model (OR=0.92, 95%CI=0.79-1.07, P=0.279), and Ala allele versus Val allele (OR=0.96, 95%CI=0.86-1.07, P=0.427). In the subgroup analysis stratified by ethnicity and sources of controls, there were also no significant associations detected among different descent populations, population-based studies and hospital-based studies.


This meta-analysis showed the evidence that MTHFR Ala222Val polymorphism was not contributed to the development of bladder cancer.

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Polymorphism; Bladder cancer; MTFHR; Ala222Val; Meta-analysis