Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis

Zhao, Mengmeng; Li, Xuelian; Xing, Chengzhong; Zhou, Baosen

doi:10.3892/br.2013.134

Cited by 36 publications

(37 citation statements)

References 59 publications

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“…Our result of a potentially protective effect of the MTHFR rs1801133 CT/TT genotype on CRC is in accordance with previous findings21222324. The primary function of MTHFR is to catalyse the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate25.…”

Section: Discussionsupporting

confidence: 92%

Alcohol consumption, genetic variants in the alcohol- and folate metabolic pathways and colorectal cancer risk: the JPHC Study

Svensson

Yamaji²,

Budhathoki³

et al. 2016

Sci Rep

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The association between alcohol intake and colorectal cancer (CRC) may vary secondary to single nucleotide polymorphisms (SNPs) in two pathways related to alcohol intake. 375 cases of CRC were identified among 38 373 Japan Public Health Center-based prospective Study (JPHC Study) participants who had returned a baseline questionnaire, reported no diagnosis of any cancer and provided blood samples. For each case, two controls were selected on matching variables. Logistic regression models were used to determine matched Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between alcohol consumption, genetic polymorphisms of enzymes in the alcohol- and folate metabolic pathways (e.g. methylenetetrahydrofolate reductase (MTHFR) rs1801133) and CRC risk. Compared to never/occasional alcohol intake, moderate to heavy alcohol intake was associated with CRC (OR = 2.12, 95% CI, 1.34–3.36). When compared to the CC genotype, the MTHFR rs1801133 CT/TT genotype was inversely associated with CRC (OR = 0.72, 95% CI, 0.54–0.97). Never/occasional consumers of alcohol with the MTHFR rs1801133 CT/TT genotype were also at a reduced risk of CRC compared to never/occasional drinkers with the CC genotype (OR = 0.68, 95% CI, 0.47–0.98) (P for interaction = 0.27). The results indicate that the folate pathway is likely to be involved in alcohol-related CRC development.

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Section: Discussionsupporting

confidence: 92%

Alcohol consumption, genetic variants in the alcohol- and folate metabolic pathways and colorectal cancer risk: the JPHC Study

Svensson

Yamaji²,

Budhathoki³

et al. 2016

Sci Rep

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“…Homozygosity for the T allele is associated with reduced enzyme activity (up to 70 % lower), around 20-25 % lower serum folate and higher plasma total homocysteine concentrations compared with the 677CC genotype (Jacques et al, 1996;Davis et al, 2005;Hustad et al, 2007). Meta-analyses have shown that the 677TT genotype is associated with a reduced risk of colorectal cancer (Huang et al, 2007;Zhao et al, 2013), but with an increased risk of neural tube defect (NTD)affected pregnancies (Vollset and Botto, 2005), pregnancy complications (Nelen et al, 2000;Kosmas et al, 2004), stroke (Casas et al, 2005;Cronin et al, 2005), schizophrenia (Muntjewerff et al, 2006;Gilbody et al, 2007) and depression (Gilbody et al, 2007). Reduced global DNA methylation was shown in individuals with the 677TT genotype in one study (Friso et al, 2002); however, the evidence is inconsistent, as this was not confirmed in two other studies (Shelnutt et al, 2004;Davis et al, 2005).…”

Section: Effects Of Genotypesmentioning

confidence: 99%

Scientific Opinion on Dietary Reference Values for folate

Products¹

2014

EFS2

106

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Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for folate. The Panel concludes that an Average Requirement (AR), as well as a Population Reference Intake (PRI) assuming a coefficient of variation (CV) of 15 % to account for the additional variability associated with the higher requirement for folate in individuals with the methylene-tetrahydrofolate reductase (MTHFR) 677TT genotype, can be derived from biomarkers of folate status. Several health outcomes possibly associated with folate intake/status were also considered, but data were found to be insufficient to establish DRVs. For adults, the AR is determined from the folate intake required to maintain folate adequacy characterised by serum and red blood cell folate concentrations of ≥ 10 and 340 nmol/L, respectively. An AR of 250 µg dietary folate equivalents (DFE)/day and a PRI of 330 µg DFE/day are derived. For infants aged 7-11 months, an Adequate Intake (AI) of 80 µg DFE/day is derived by extrapolating upwards from the estimated folate intake in exclusively breast-fed infants. For children, ARs are extrapolated from the AR for adults using allometric scaling and growth factors and considering differences in reference weights. PRIs ranging from 120 µg DFE/day for 1-3 year-old children to 330 µg DFE/day for boys and girls aged 15-17 years are derived. For pregnant women, an AI of 600 µg DFE/day is derived based on a study on maintenance of serum and red blood cell folate concentrations in pregnancy. For lactating women, an additional intake of 130 µg DFE/day is considered to cover folate losses via breast milk; this figure is added to the AR for non-lactating women and a PRI of 500 µg DFE/day is derived.

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“…Some results have reported that the 677TT genotype could cause a considerable risk reduction of CRC. In high folate intake cases, the risk of CRC risk is reduced for both MTHFR 677CC and 677TT genotypes [30].…”

Section: Discussionmentioning

confidence: 99%

Association of MTHFR C677T Variant Genotype with Serum Folate and Vit B12 in Iranian Patients with Colorectal Cancer or Adenomatous Polyps

Ghorbani

Baharara

Kerachian

2020

Preprint

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Background: The incidence of colorectal cancer (CRC) has increased vigorously during the last decades in Iran and clinical studies suggest that moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) and essential folate dietary intake may reduce the risk of CRC.The aim of this study was to investigate the clinical significance of C677T polymorphism within MTHFR gene and its correlation with the serum folate and Vit B12 in Iranian population suffering from CRC.Methods: Blood samples were taken from 207 Iranian individuals (103 males and 104 females) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Besides, sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. Finally, the correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk were analyzed.Results: In the current study, the most percentage of the MTHFR polymorphisms in healthy individuals belongs to CC genotype (wild type). In patients with adenoma the percentage of CC and CT genotype were approximately similar, but surprisingly in adenocarcinoma the percentage of CC genotype (wild type) was the highest (approximately 50%), and the percentage of CT and TT genotypes were slightly similar. Our study revealed that there was no significant difference between the amount of folate and Vit B12 in case and control groups (p value >0.05).Conclusions: We concluded that there is an association between pivotal concentration of serum folate/vitamin B12 and CRC, and this association is altered by MTHFR C677T genotype.

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Association of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms with colorectal cancer risk: A meta-analysis

Cited by 36 publications

References 59 publications

Alcohol consumption, genetic variants in the alcohol- and folate metabolic pathways and colorectal cancer risk: the JPHC Study

Alcohol consumption, genetic variants in the alcohol- and folate metabolic pathways and colorectal cancer risk: the JPHC Study

Scientific Opinion on Dietary Reference Values for folate

Association of MTHFR C677T Variant Genotype with Serum Folate and Vit B12 in Iranian Patients with Colorectal Cancer or Adenomatous Polyps

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