Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

Abstract

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case-control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16-3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05-1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4-6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03-2.53) compared with those with 0-3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03-2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer.

Genetic susceptibility of methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms with risk for bladder transitional cell carcinoma in men

“…Their meta-analysis indicated that the MTHFR C677T polymorphism was not associated with bladder cancer risk, which was consistent with our findings. However, Wang et al [17] in their own study found an increased risk effect for 677T allele on risk of bladder cancer which is in contrary with our results and published data in literature. There is significant heterogeneity for MTHFR gene polymorphisms among the different populations.…”

“…The novel MTHFR 1793A variant is rare in Caucasians, and the allele frequency in our study population was consistent with that reported by Rady et al [16]. Wang et al [17] performed a meta-analysis on the effect of polymorphism in MTHFR gene and bladder cancer risk. They analyzed seven published literatures.…”

“…Studies addressing the effect of MTHFR gene polymorphisms on bladder cancer are very scarce and conflicting. Wang et al [17] reported that the subjects carrying MTHFR 677TT genotype had statistically significantly increased risk of bladder TCC compared with the 677CC genotype. In the same study, the authors performed a meta-analysis of seven studies and did not find a significant risk of bladder cancer in the MTHFR polymorphisms.…”

Lack of association between MTHFR Ala222Val and Glu429Ala polymorphisms and bladder cancer risk: A meta-analysis of case-control studies

“…A total of 11 studies (5–7,18–21,23,25–27) were included in this meta-analysis for Ala222Val (including 3,463 cases and 3,.927 controls) and 9 studies (5–7,19–21,23,25,27) were included for Glu429Ala (including 3,177 cases and 3,502 controls) (Table I). Three of the 11 studies were population-based and eight were hospital-based studies.…”

Genetic Variation Throughout the Folate Metabolic Pathway Influences Negative Symptom Severity in Schizophrenia

“…Using a similar approach, other investigators have identified pooled effects of folate-related genes on cancer risk. 39,40 The approach of canvassing genetic variants in implicated biological pathways to generate cumulative risk scores holds promise in resolving the so-called ''missing heritability'' in schizophrenia and other complex genetic disorders in psychiatry 41 -just as in the present study, where the net effects of folate-related variants outweighed the influence of MTHFR 677C>T alone on negative symptom severity.…”