Using gene-environment interaction analyses to clarify the role of well-done meat and heterocyclic amine exposure in the etiology of colorectal polyps

Background: The role of well-done meat intake and meat-derived mutagen heterocyclic amine (HCA) exposure in the risk of colorectal neoplasm has been suggested but not yet established. Objective: With the use of gene-environment interaction analyses, we sought to clarify the association of HCA exposure with colorectal polyp risk. Design: In a case-control study including 2057 colorectal polyp patients and 3329 controls, we evaluated 16 functional genetic variants to construct an HCA-metabolizing score. To derive dietary HCA-exposure amount, data were collected regarding dietary intake of meat by cooking method and degree of doneness. Results: A 2-fold elevated risk associated with high red meat intake was found for colorectal polyps or adenomas in subjects with a high HCA-metabolizing risk score, whereas the risk was 1.3- to 1.4-fold among those with a low risk score (P-interaction ≤ 0.05). The interaction was stronger for the risk of advanced or multiple adenomas, in which an OR of 2.8 (95% CI: 1.8, 4.6) was observed for those with both a high HCA-risk score and high red meat intake (P-interaction = 0.01). No statistically significant interaction was found in analyses that used specific HCA exposure derived from dietary data. Conclusion: High red meat intake is associated with an elevated risk of colorectal polyps, and this association may be synergistically modified by genetic factors involved in HCA metabolism.