A common C to T transition (C677T) in the MTHFR gene is reported to reduce the risk for colorectal cancer and acute lymphocytic leukemia in homozygotes (TTs).
We conclude that the MTHFR 1298A>C polymorphism is a less substantial independent risk factor for colorectal cancer compared to the 677C>T polymorphism.
This population-based case-control study was designed to investigate the interrelationships between polymorphisms in the methylenetetrahydrofolate (MTHFR C677T and A1298C) gene and other genes (MTR A2756G; MTRR A66G and CBS 844ins68), intake of B-vitamins and colorectal cancer risk (CRC).
Colorectal cancer and the methylenetetrahydrofolate reductase 677C -> T and methionine synthase 2756A -> G polymorphisms: a study of 2,168 case-control pairs from the JANUS cohort.
Different polymorphisms have been described for this enzyme, the most studied being the C677T, which has been shown to be associated with predisposition to colorectal cancer in patients who consume a high alcohol diet.
Meta analysis of these studies showed that GSTT1 deletion (pooled OR = 1.42), N-acetyltransferase 2 (NAT2)-rapid acetylator phenotype and genotye (pooled OR = 1.08) and NAT2-rapid acetylator phenotype (pooled OR = 1.15) had a significantly increased risk for colorectal cancer (P<0.05), other genotypes like GSTM1 deletion, GSTP1 1le105Val, NAT1*10, NAT2-rapid acetylator genotype CYP1A1 L1e462Val, CYP1A1 MspI*C, MTHFR C677T and MTR A2759G had no significant relationship with colorectal cancer (P>0.05).
Although the underlying mechanisms still remain to be clarified, epidemiological findings regarding MTHFR C677T polymorphism provide strong evidence that adequate folate status confers protection from colorectal cancer.
Although the mechanism responsible for the link between the C677T polymorphism and microsatellite instability was not apparent, this finding may provide a clue towards a better understanding of the pathogenesis of microsatellite instability in human colorectal cancer.
MTHFR C677T polymorphism may not be important in an individual's susceptibility to gastric and colorectal cancer in Turkey and may not be a useful marker for identifying patients at high risk of developing gastric and colorectal cancer.
The protective effect of the homozygous variant TT form of the MTHFR genotype (C677T) on the risk of colorectal cancer seems to be modified by the level of methyl diets, that is, by folate, which has a protective effect, or conversely by alcohol.
This is the first report to our knowledge to provide evidence that the C677T</span> polymorphism modifies the age at onset of colorectal cancer in Caucasian Lynch syndrome subjects with the 677T allele having a protective effect.
We report a population-based case-control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake.
Certain common polymorphisms within the MTHFR gene (C677T, A1298C) result in reduced enzymatic activity and have been associated with reduced risk for a variety of cancers such as acute lymphocytic leukemia, lung and colorectal cancer.
Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status.
To study the relation between genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the susceptibility of colorectal cancer.
The available evidence indicates that MTHFR C677T and A1298C gene polymorphisms cannot be considered as reliable predictors of response to fluorouracil-based chemotherapy in patients with colorectal cancer.