Abstract Colorectal polyps are the precursors of colorectal cancer, the second leading cause of cancer death in the United States. Red and processed meat intakes have been associated with an increased risk of conventional colorectal adenomas and are classified as carcinogens by the World Health Organization. The mechanism for the relationship between red and processed meat intakes and adenoma risk remains unclear. An explanation may be the exposure to mutagens derived from meat including heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are formed by cooking meats at high temperatures. Although intakes of these meats and mutagens has been associated with risks of conventional adenomas including in our study, no previous study has evaluated risk of sessile serrated polyp (SSPs). SSPs, a more recently recognized precursor lesion for microsatellite instable cancer, were strongly associated with red meat intake in our earlier study. This new study builds on that work by evaluating the associations between meat intake, meat cooking methods, and meat mutagens with risks of SSPs and compares the risks to conventional adenomas and hyperplastic polyps. The analysis is conducted in the Tennessee Colorectal Polyp Study, using polytomous logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). Dietary information was collected by a self-administered food frequency questionnaire and telephone interview to ascertain meat intake and doneness. This information was used to estimate the intakes of meats, well-done meats, PAHs, HCAs, and mutagenic activity. Several measures of meat intake were strongly associated with risk of SSPs. Highest quartile levels of total meat intake (OR=2.04; 95% CI: 1.24-3.36, p for trend=0.002), red meat intake (OR=2.32; 95% CI: 1.37-3.91, p for trend<0.001), processed meat intake (OR=1.99, 95% CI: 1.24-3.20, p for trend=0.004), well-done red meat (OR=2.13, 95% CI: 1.28-3.55, p for trend=0.002), well-done processed meat (OR=1.60, 95% CI: 1.06-2.4, p for trend=0.03), and the HCA MeIQx (OR=2.55, 95% CI: 1.50-4.33, p for trend=0.003) were associated with statistically significantly increased risks of SSP in comparison to the lowest intake levels. Most of these associations were stronger for risk of SSP than for the other types of polyps. In particular, MeIQx intake was not associated with risk of conventional adenomas suggesting that the mechanisms by which red meat intake affects polyp risk may be different between the conventional adenoma and serrated pathways. Future studies are needed to confirm the relationship between meat and meat mutagen intake with SSP risk and to further define the mechanism(s) by which intake of these factors affects SSP risk. Citation Format: Dominique A. Mosley, Harvey J. Murff, Reid M. Ness, Walter E. Smalley, Wei Zheng, Martha J. Shrubsole. The association of meat intake, meat cooking methods, and meat-derived mutagen exposure with the risk of sessile serrated polyps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 964.