We observed an inverse association of a polymorphism (667C --> T, ala --> val) in the methylenetetrahydrofolate reductase (MTHFR) gene with colorectal cancer but not with colorectal adenomas.
MTHFR genotypes were ascertained from peripheral leukocyte samples obtained from 200 colorectal patients, including TMN stages I-VI, and from 460 healthy, unrelated adults without colorectal cancer, who served as controls.
Studies of the interaction between polymorphisms in the gene for methylenetetrahydrofolate reductase (MTHFR) and dietary components for risk of both colorectal cancer and adenomatous polyps provide a glimpse into the future of diet and cancer research.
A homozygous mutation at bp 677 in the gene for the methylenetetrahydrofolate reductase (MTHFR) was previously shown to be associated with a decreased risk of colorectal cancer.
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).
This population-based case-control study was designed to investigate the interrelationships between polymorphisms in the methylenetetrahydrofolate (MTHFRC677T and A1298C) gene and other genes (MTR A2756G; MTRR A66G and CBS 844ins68), intake of B-vitamins and colorectal cancer risk (CRC).
Overall homozygosity for MTHFR variant genotypes is associated with a reduced risk of colorectal cancer, the opposite of what might have been expected a priori.
Whereas our results do not support an association of high enzyme activity and increased risk of colorectal cancer in general, we can not exclude an association of patients with hereditary disease and the MTHFR 1298A --> C variant.
In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk.
We evaluated the relation between the polymorphisms 677C --> T of the methylenetetrahydrofolate reductase (MTHFR) and 2756A --> G of the methionine synthase (MTR) genes and risk of colorectal cancer.
The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis.
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, MTHFRC677T and MTR A2759G had no significant relationship with colorectal cancer (P>0.05).
We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population.
Relationship of the methylenetetrahydrofolate reductaseC677T polymorphism with microsatellite instability and promoter hypermethylation in sporadic colorectal cancer.
The results suggest that the MTHFR genotype cannot be considered as an independent factor of outcome in colorectal cancer patients under 5-FU-based chemotherapy.