Are Polymorphisms of MTHFR Genes a Prostate Cancer Risk?

Among the many possible causes of prostate cancer is one you’ve probably never heard about before and one that requires some explanation: polymorphisms of MTHFR genes. A polymorphism occurs when two or more different characteristics of an organism exist in the same species. How could polymorphisms increase the risk of prostate cancer?

At Shahid Beheshti University in Tehran, Iran, researchers explored the possibility that genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene is associated with an increased risk of prostate cancer.  The MTHFR gene provides instructions for making methylenetetrahydrofolate reductase, an enzyme that has a major role in processing amino acids, in reactions involving folate and in converting the amino acid homocysteine to methionine, another amino acid, which is used to make proteins.

The researchers analyzed the genetic makeup of three MTHFR polymorphisms (C677T, A1298C, and G1793A) and measured the levels of homocysteine, folate, and vitamin B12 levels in 174 men with prostate cancer and 348 healthy controls. (Note: The letter suffixes on the polymorphisms and genotypes refer to the four different bases that make up genes: A=adenine, C=cytosine, G=guanine, T=thymine.)

The MTHFR 677TT and 1298CC genotypes were associated with about a 40% reduced risk of prostate cancer compared with 677CC and 1298AA genotypes. The combination of 1298AC and 677CC were associated with a 30% reduced risk of prostate cancer.

However, a slightly increased risk of prostate cancer was seen with the variant genotypes 1793GA plus 677CT. The investigators also found that the 677TT genotype was associated with a greater than 50% reduced risk of high-grade prostate cancer when compared with the 677CC and 677CT genotypes. Levels of homocysteine, folate, and vitamin B12 were not significantly different between the two groups regardless of genotype.

The authors concluded that the three MTHFR polymorphisms they studied may have an important part to play in the development of prostate cancer.

Read more in our Prostate Cancer Health Center.


Safarinejad MR et al. Relationship between three polymorphisms of methylenetetrahydrofolte reductase (MTHFR C677T, A1298C, and G1793A) gene and risk of prostate cancer: a case-control study. Prostate 2010 Nov 1; 70(15): 1645-57

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