Association between methylenetetrahydrofolate reductase gene rs1801131 A/C polymorphism and urinary tumors\u2019 susceptibility

Shuaili Xu,Li Zuo

doi:10.1186/s41065-020-00129-x

Abstract

BackgroundThe methylenetetrahydrofolate reductase (MTHFR) rs1801131 A/C variant results in a decrease in MTHFR enzymatic activity, which may play an important role in folate metabolism and is also an important source of DNA methylation and DNA synthesis. Several case-control studies have been conducted to assess the association of MTHFR rs1801131 polymorphism with the risk of urinary cancers, yet with conflicting conclusions. To derive a more precise estimation of above relationship, the association between the MTHFR rs1801131 A/C polymorphism and the risk of urinary cancer was performed.MethodsA total of 28 case-control studies was identified. The odds ratios (OR) with 95% confidence intervals (CI) was calculated to assess.ResultsOn one hand, we found that the MTHFR rs1801131 A/C polymorphism was associated with increased whole urinary cancers’ risk (for example CA vs. AA: OR = 1.12. 95%CI = 1.01–1.24). On the other hand, we found that the MTHFR rs1801131 A/C polymorphism might increase bladder cancer risk both in Asian (C-allele vs. A-allele: OR = 1.35. 95%CI = 1.15–1.60) and African populations (CA vs. AA: OR = 1.63. 95%CI = 1.17–2.25).ConclusionsOur current analysis suggested that MTHFR rs1801131 A/C is associated with urinary cancers, especially bladder cancer.

Highlights

The methylenetetrahydrofolate reductase (MTHFR) rs1801131 A/C variant results in a decrease in MTHFR enzymatic activity, which may play an important role in folate metabolism and is an important source of DNA methylation and DNA synthesis
On one hand, we found that the MTHFR rs1801131 A/C polymorphism was associated with increased whole urinary cancers’ risk
We found that the MTHFR rs1801131 A/C polymorphism might increase bladder cancer risk both in Asian (C-allele vs. A-allele: Odds ratios (ORs) = 1.35. 95%confidence intervals (CI) = 1.15–1.60) and African populations (CA vs. AA: OR = 1.63. 95%CI = 1.17–2.25)

Summary

Results

Abstract, and full text, 51 different papers were included for the final analysis, expect for papers focusing on meta-analyses, reviews, case-only studies, and other gene polymorphisms. To avoid publishing bias, two papers that were not consistent with HWE were excluded, so 9 casecontrol studies were left for analysis, and, to our regret, no association was detected. Based on ethnicity-stratified and source of control subgroup analysis, there remain no significant association were found (Table 2). In the subgroup analysis in source of control, increased relationship was detected in dominant genetic model (OR = 1.29, 95% CI = 1.09–1.54, Pheterogeneity = 0.235, Fig. 7). The diamond represents the summary OR and 95% CI significantly altered, indicating that our results were statistically robust (for example: allelic contrast, Fig. 11) To verify this association, we used the PolyPhen-2 tool to analyze the features of the rs1801131 mutant.

Background

Design Source of control

Discussion