Introduction: Methionine and its metabolic derivatives regulate activity of most methyltransferases and activity of several enzymes involved in one-carbon metabolism. S-adenosylmethionine (SAM), the direct metabolite of methionine, is the methyl donor for nearly all methylation reactions in the body. SAM is irreversibly converted to S-adenosylhomocysteine (SAH), the metabolic precursor of homocysteine. SAH is a potent inhibitor of all methyltransferases. Very few studies have evaluated biological measures of methionine and its metabolites with colorectal cancer. Recently, a large cross-sectional study found plasma methionine was associated with a reduced risk of distal colorectal adenoma. To our best knowledge, no study has evaluated SAM or SAH with colorectal cancer or adenoma. Methods: In this study, we evaluated plasma levels of these markers with risk for colorectal adenoma using a colonoscopy-based matched case-control design. Participants were part of a large case-control study of colorectal adenoma. A subset of cases were individually matched to polyp-free controls in a 1:1 ratio on age, sex, race, study site and date of sample collection. Included in the analysis were 220 pairs of adenoma cases and polyp-free controls. SAM and SAH were measured in a single assay by high-performance liquid chromatography. Sex-specific quantile cutpoints were derived using the distributions among controls. Conditional logistic regression models were used to derive odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations with colorectal adenoma risk after adjusting for age, and other potential confounders. All of the reported P values were two-tailed, and statistical significance was set at 0.05. Result: A statistically significant interaction between sex, SAH or SAM, and adenoma risk was observed. Among women, high SAH was associated with a borderline statistically significant increased risk of adenoma (p for trend=0.08). Among men, both high SAH (OR=0.36, 95% CI: 0.16-0.78, p for trend=0.009) and high SAM (OR=0.41, 95% CI: 0.19-0.88, p for trend=0.02) were associated with decreased risks of adenoma. The joint association of SAM and SAH was also evaluated among men. In comparison to men with low SAH and low SAM, men with high SAM and high SAH had a reduced risk of colorectal adenoma. Conclusion: The findings reported in this study are new, suggesting SAH and SAM may be involved in the development of colorectal adenoma. Further studies are warranted.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4469. doi:1538-7445.AM2012-4469