Evaluation of Association Studies and Meta-Analyses of
            <i>MTHFR</i>
            Gene Polymorphisms in Colorectal Cancer

Haerian, Batoul Sadat; Haerian, Monir Sadat

doi:10.2217/pgs.14.177

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…Consistent with the reports from previous meta-analyses, in the present pooled analyses for all populations, MTHFR 677 homozygous mutation TT genotype presented as a protective genotype for CRC with statistical significance ( p < .05); however, there were heterogeneity and opposing findings for the subgroup of Hispanics ( p < .01). Previous meta-analyses consistently indicated heterogeneity or discrepancies for MTHFR and CRC risk for various populations, perhaps due in part to the dominant population stratification from Australia, the United States, and Brazil ( Haerian & Haerian, 2015 ). In this meta-analysis study, the subgroup analysis with those countries that had findings contrary to those majority countries with the MTHFR 677 TT homozygous mutation genotype as a protective type was revealing to delineate the impacts of population stratification.…”

Section: Discussionmentioning

confidence: 99%

Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer

Shiao

2016

Biological Research For Nursing

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The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most investigated of the genes associated with chronic human diseases because of its associations with hyperhomocysteinemia and toxicity. It has been proposed as a prototype gene for the prevention of colorectal cancer (CRC). The major objectives of this meta-analysis were to examine the polymorphism-mutation patterns of MTHFR and their associations with risk for CRC as well as potential contributing factors for mutations and disease risks. This analysis included 33,626 CRC cases and 48,688 controls across 92 studies for MTHFR 677 and 16,367 cases and 24,874 controls across 54 studies for MTHFR 1298, comprising data for various racial and ethnic groups, both genders, and multiple cancer sites. MTHFR 677 homozygous TT genotype was protective (p < .05) for CRC for all included populations; however, with heterogeneity across various racial–ethnic groups and opposing findings, it was a risk genotype for the subgroup of Hispanics (p < .01). Additional countries for which subgroup analyses resulted in 677 TT as a risk genotype included Turkey, Romania, Croatia, Hungary, Portugal, Mexico, Brazil, U.S. Hawai’i, Taiwan, India, and Egypt. Countries with the highest mutation rates and risks for both MTHFR 677 and 1298 genotypes are presented using global maps to visualize the grouping patterns. Meta-predictive analyses revealed that air pollution levels were associated with gene polymorphisms for both genotypes. Future nursing research should be conducted to develop proactive measures to protect populations in cities where air pollution causes more deaths.

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Section: Discussionmentioning

confidence: 99%

Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer

Shiao

2016

Biological Research For Nursing

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“…Linkage disequilibrium among the variants can vary across populations . For example, Haerian and Haerian showed that rs1801133 and rs1801131 might be CRC susceptibility variants in Americans and Australians, whereas rs1801133 may be more common in the Brazilian and Japanese populations. Based on these results, patients of different ethnicities may carry different rs1801133 and rs1801131 variants.…”

Section: Methodsmentioning

confidence: 99%

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta‐analysis

Chen

Wang

Zhao

et al. 2019

The Journal of Gene Medicine

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BackgroundThe present study focused on understanding the prognostic value of the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms rs1801133 (C667T) and rs1801131 (A1298C) in patients with colorectal cancer (CRC).MethodsA systematic literature search was conducted in March 2016. Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC. Data regarding overall survival (OS), progression‐free survival (PFS) and disease‐free survival (DFS) were collected and analysed.ResultsTwenty‐four studies with 5423 patients with CRC were included. Significant differences in OS, PFS and DFS were not observed among the different comparisons of patients carrying different alleles of the MTHFR rs1801133 polymorphism (including TT versus CC, TT versus CT + CC, CT + TT versus CC and CT versus CC). Compared with patients with the rs1801131 CA + AA genotypes, patients with the CC genotype had a shorter OS (hazard ratio = 1.85; 95% confidence interval = 1.30–2.65) and DFS (hazard ratio = 2.16; 95% confidence interval= 1.19–3.93). Significant differences in OS, PFS and DFS were not observed among the other patient groups (including CC versus AA, CC + CA versus AA and CA versus AA). Subgroup analysis of rs1801133 and rs1801131 showed that patients with CRC from Asian regions and Western regions demonstrated similar results.ConclusionsThe MTHFR rs1801133 polymorphism was not associated with the prognosis of patients with CRC; however, rs1801131 may be associated with the prognosis of patients with CRC. Well‐designed prospective studies are necessary to obtain a better understanding of the prognostic value of rs1801133 and rs1801131.

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“…In recent years, there were several meta-analyses performed to elucidate the association of MTHFR C677T polymorphism and the susceptibility to CRC before [ 26 , 115 – 118 ]. Compared with them, this meta-analysis included the most eligible reported studies with the largest sample size and had no restrictions in ethnicity.…”

Section: Discussionmentioning

confidence: 99%

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

Qin

Wang

et al. 2017

Bioscience Reports

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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.

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Evaluation of Association Studies and Meta-Analyses of MTHFR Gene Polymorphisms in Colorectal Cancer

Cited by 7 publications

References 35 publications

Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer

Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer

Methylenetetrahydrofolate reductase polymorphisms and colorectal cancer prognosis: A meta‐analysis

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

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