Purpose: We investigated whether the mutant methylenetetrahydrofolate reductase (MTHFR) increases risk for oral cancer. The common germ-line mutation C677T in the MTHFR gene significantly diminishes specific activity of the enzyme, which is responsible for the circulating form of folate. Folate deficiency is associated with increased risk for thrombosis, as well as for several types of cancer, through disruption of DNA methylation, DNA synthesis and deficient DNA repair.
Methods: We searched for the C677T mutation by restriction fragment analysis of PCR products in DNA samples of 110 patients with oral squamous cell carcinoma and 120 healthy controls of comparable ethnicity, age and sex.
Results: The number of heterozygotes was significantly different in the two groups (P<0.005), as well as in subgroups of patients with or without a positive family history for cancer, compared to normal controls (P<0.01 and P<0.005, respectively). Furthermore, the subgroup of patients with a positive family history for thrombophilia had a significant increase both in the frequencies of mutant alleles (P<0.01) and heterozygotes (P<0.001) in comparison to normal controls.
Conclusions: The obtained results suggest that the MTHFR mutation is a minor contributing factor in oncogenesis in the oral region, in conjunction with low dietary uptake of folate.