What is it about?

Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated whether MTHFR C677T, A1298C and G1793A polymorphisms modified clear cell renal cell carcinoma (CCRCC) risk independently as well as in combination with serum total homocysteine (Hcy) and folate levels.

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Why is it important?

Renal cell carcinoma (RCC), also called renal adenocarcinoma or hypernephroma, is the third leading cause of death among urological tumours. It accounts for 3% of all adult malignancies. Epidemiological studies have suggested that several demographic, clinical and environmental factors, such as gender, hypertension and smoking, and several drugs, including diuretics, aspirin and phenacetin, are implicated in the occurrence of RCC. However, only a small fraction of individuals exposed to these risk factors develop RCC. The association between RCC and several genetic polymorphisms has been reported by several authors.


A reduced enzyme activity due to an increased thermolability has been shownfor the 677TTand 1298CC genotypes in the humanMTHFR gene. The 1298AC variant interacts with the T allele at position 677 in reducing the MTHFR enzyme activity and reduced plasma folate level. An increased risk of carcinogenesis with the wild-type genotypes (and wild-type levels of enzyme activity) might be explained by DNA damage due to DNA double-strand breaks based on uracil incorporation. Adecreased risk associated with the wild-type genotypes (and wild-type levels of enzyme activity) might be described by a reduced risk of hypomethylation, a widespread feature of carcinomas.

Dr Mohammad Reza Safarinejad
University of Medical Sceices

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This page is a summary of: Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T, A1298C and G1793A Polymorphisms: Association with Risk for Clear Cell Renal Cell Carcinoma and Tumour Behaviour in Men, Clinical Oncology, May 2012, Elsevier,
DOI: 10.1016/j.clon.2011.03.005.
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