Abstract
BackgroundThe association between Methylenetetrahydrofolate reductase (MTHFR) Ala222Val (rs1801133) has been implicated to alter the risk of bladder cancer, but the results are controversial.MethodsA 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.ResultsA 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.ConclusionThis meta-analysis showed the evidence that MTHFR Ala222Val polymorphism was not contributed to the development of bladder cancer.Virtual slideThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2117182849994994.
Highlights
Bladder cancer is the second most common genitourinary malignant disease, with an expected 73,510 newly diagnosed cases and 14,880 deaths in 2012 in America [1]
Our analysis suggested that Ala222Val was not associated with bladder cancer risk in overall population under additive model (OR=0.96, 95% confidence intervals (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 no significant associations detected among different descent populations, population-based studies and hospital-based studies
Summary
Bladder cancer is the second most common genitourinary malignant disease, with an expected 73,510 newly diagnosed cases and 14,880 deaths in 2012 in America [1]. Host factors including genetic polymorphisms, have been suggested as risk factors for the development of a variety of cancers, including bladder cancer. Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene are receiving increasing attention as variants that may potentially influence methyl group metabolism and, thereby, alter chromosome integrity. If MTHFR polymorphic variants reduce folate levels by diminishing enzymatic activity, they could enhance the propensity for DNA strand breakage and cancer occurrence [6]. Variant MTHFR activity could influence the availability of methyl donors by altering S-adeno-sylmethionine levels, and potentially, the methylation status of key tumor suppressor or promoter genes involved in bladder carcinogenesis [7]. The association between Methylenetetrahydrofolate reductase (MTHFR) Ala222Val (rs1801133) has been implicated to alter the risk of bladder cancer, but the results are controversial
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