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Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis.

ABSTRACT: The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer (CRC) susceptibility has been researched in numerous studies. However, the results of these studies were controversial. Therefore, the objective of this meta-analysis was to offer a more convincible conclusion about such association with more included studies. Eligible studies published till May 1, 2017 were searched from PubMed, Embase, Web of Science, and CNKI database about such association. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated to evaluate such association. And the Begg's funnel plot and Egger's test were applied to assess the publication bias. This meta-analysis contained 37049 cases and 52444 controls from 87 publications with 91 eligible case-control studies. Because of lack of data for a particular genotype in several studies, all the included studies were analysed barely in the dominant model. Originally, there was no association between MTHFR C677T polymorphism and CRC susceptibility (OR =0.99, 95% CI =0.94-1.05). After excluding 13 studies according to their heterogeneity and publication bias, rs1801133 polymorphism was found to reduce the risks of CRC significantly (OR =0.96, 95% CI =0.94-0.99). In the subgroup analysis of ethnicity, there was a significant association in Asians (OR =0.94, 95% CI =0.89-1.00). Furthermore, when stratified by the source of controls and genotyping methods, the positive results were observed in population-based control group (OR =0.97, 95% CI =0.93-1.00) and PCR-restriction fragment length polymorphism (PCR-RFLP) method (OR =0.95, 95% CI =0.91-0.99. The results of the meta-analysis suggested that MTHFR C677T polymorphism was associated with CRC susceptibility, especially in Asian population.

SUBMITTER: Xu L

PROVIDER: S-EPMC5719002 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis.

Xu Lingyan L Qin Zhiqiang Z Wang Feng F Si Shuhui S Li Lele L Lin Peinan P Han Xiao X Cai Xiaomin X Yang Haiwei H Gu Yanhong Y

Bioscience reports 20171207 6

The association between methylenetetrahydrofolate reductase (<i>MTHFR</i>) C677T polymorphism and colorectal cancer (CRC) susceptibility has been researched in numerous studies. However, the results of these studies were controversial. Therefore, the objective of this meta-analysis was to offer a more convincible conclusion about such association with more included studies. Eligible studies published till May 1, 2017 were searched from PubMed, Embase, Web of Science, and CNKI database about such ...[more]

PMID: 29089462

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Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate. The non-synonymous single nucleotide polymorphism (nsSNP), C677T (Ala>Val, rs1801133), has been verified to impair enzyme activity. The association with cancer susceptibility, including hepatocellular carcinoma (HCC), has also been widely studied. The results, however, were inconsistent. To shed light on the influence of MTHFR C677T polymorphism on HCC, a meta-analysis was conducted.MethodsThe meta-analysis of C677T consisted of 10 studies (1814 cases/2862 controls). The association was measured by using random-effect (RE) or fixed-effect (FE) odds ratio (OR) combined with 95% confidence intervals (CIs) according to the studies' heterogeneity.ResultsUsing genetic model analysis, C677T polymorphism was found to increase the risk of HCC in a complete overdominant model, which indicates that heterozygotes CT are at a lesser risk of HCC than either homozygotes CC or TT. Meta-analyses of the 10 studies showed that the TT genotype increased the risk of HCC as compared to the CT genotype: FE OR was 1.20 (95%CI: 1.00-1.45, p for heterogeneity = 0.21). When subgroup analysis was done between the HCC cases and the chronic liver disease (CLD) patients of four studies, meta-analysis showed that individuals with the TT genotype had increased HCC risk compared with those with the CT genotype: FE OR (TT vs. CT) reached 1.81 (1.22-2.71, p for heterogeneity = 0.25). Meanwhile, the C677T polymorphism also increased HCC risk in a recessive model when cases were compared to CLD patients of four studies: RE OR reached 1.85 (95%CI: 1.00-3.42, p for heterogeneity = 0.06). Overall, there was some extent heterogeneity when analyses were performed in various models. There was no publication bias.ConclusionMTHFR C677T polymorphism increased the risk of HCC in an overdominant model, and might be a risk factor for HCC occurrence, especially in CLD patients. The association warranted further studies.

Dataset Information

Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis.

Publications

Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis.

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