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.