Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum

Most studies demonstrate increased risk of colorectal cancer (CRC) and aden omas in folate-deficient subjects or that high folate intake may afford som e protection. Smoking increases such risk in some but not all studies. We i nvestigated whether smoking, folate status and methylenetetrahydrofolate re ductase (MTHFR) genotype predict the risk of adenomatous and hyperplastic p olyps of colorectum. By colonoscopy, the type, number, size and extent of d ysplasia of colorectal polyps were assessed in 443 subjects aged 63-72 year s. We also determined RBC folate and the C667T polymorphism of the methylen etetrahydrofolate reductase (MTHFR) gene. Smoking, folate status and the C6 77T MTHFR polymorphism were strong, interactive determinants of highrisk ad enomas (HRAs, defined as adenomas greater than or equal to 10 mm in diamete r, adenomas with villous components or with severe dysplasia). The risk was particularly high in smokers with low folate and the CT/TT genotype (risk category T) and in smokers with high folate and the CC genotype (risk categ ory C). With non-smokers with low folate and the CC genotype as reference, the odds ratios (OR, 95% CI) were 8.7 (2.5-29.7) in category T and 9.9 (2.6 -38.4) in category C. Notably, this risk pattern was also observed for hype rplastic polyps. In conclusion, in smokers, high folate status may confer i ncreased or decreased risk for HRAs, depending on the MTHFR genotype. These data demonstrate the strong gene-nutrition interaction involving the C677T MTHFR polymorphism. (C) 2001 Wiley-Liss, Inc.