Effect of 677 C to T mutations in the methylenetetrahydrofolate reductase gene, folate intake and plasma homocysteine on adenoma recurrence

The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, associated with the thermolabile form of the enzyme, has been shown to influence risk of colorectal neoplasia. We examined the effect of modification of this mutation on the association between plasma homocysteine or folate intake and adenoma recurrence among 703 individuals with a history of resected adenomas. We analyzed homocysteine at baseline by high-peformance liquid chromatography and assessed dietary folate with a food-frequency questionnaire. The prevalence of the 677TT genotype was 10.8%. A higher risk of adenoma recurrence was shown among the following groups: individuals with the 677TT genotype compared with those with the 677CC wild type (odds ratio [OR]=1.60; 95% confidence interval [CI]=0.93–2.74); individuals in the lowest tertile of folate intake compared with those in the highest (OR=1.42; 95% CI=0.96–2.10); individuals with plasma homocysteine levels above compared with those below 9.5 μmol l⁻¹ (OR=1.49; 95% CI=1.01–2.21). When assessing the interaction of folate and MTHFR, we found the highest risk of adenoma recurrence in individuals with folate intakes of 370 μg day⁻¹ or lower and the 677TT genotype as compared with those with intakes greater than 370 μg day⁻¹ and 677CC or 677CT MTHFR genotypes (OR=2.16; 95% CI=1.00–4.69). For the interaction of plasma homocysteine and MTHFR, the OR for individuals with homocysteine levels greater than 9.5 μmol l⁻¹ and the 677TT variant was 5.87 (95% CI=1.51–22.8) compared with those with levels of 9.5 μmol l⁻¹ or lower and 677CC or 677CT MTHFR genotypes. These data indicate that the association between folate status and adenoma recurrence is influenced by the MTHFR polymorphism.