Reverse association between MTHFR polymorphism (C677T) with sporadic colorectal cancer

To investigate association between MTHFR gene polymorphism with colorectal cancer The enzyme 5,10-methylene-tetrahydrofolate reductase (MTHFR) is linked to DNA methylation, synthesis and repair. One of the most important polymorphisms that has been identified in the MTHFR gene is C677T. The single nucleotide polymorphism C677T has been found to be associated with decreased enzyme activity and decreased plasma folate. Thus it might play an important role in the etiology of colorectal neoplasia. Patients and Using pyrosequencing, we analyzed the MTHFR genotypes in 234 colorectal cancer patients and 257 normal matched controls. Whereas the CC, CT and TT genotypes of MTHFR among the colorectal cancer patients were 50%, 29% and 21% respectively, we found 36.6% of 677CC, 31.1% of 677CT and 32.3% of 677TT in the normal controls. We observed a decreased risk of colon cancer when folate intake was high for participants with wild type genotype. This association was stronger at higher levels of folate intake. Our study corroborates previous findings of an inverse association of the MTHFR 677TT genotype with colorectal cancer, especially at high levels of folate.