Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis

Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene (B(a)P) and “meat derived mutagenic activity” (MDM)) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR = 1.20; 95% CI: 1.13,1.28; p < 0.001), MeIQx (OR = 1.14; 95% CI: 1.05,1.23; p = 0.001), DiMeIQx (OR = 1.13; 95% CI: 1.05,1.21; p = 0.001), B(a)P (OR = 1.10; 95% CI: 1.02,1.19; p = 0.017) and MDM (OR = 1.17; 95% CI: 1.07,1.28; p = 0.001). A linear and curvilinear trend was observed in dose–response meta-analysis between CRA risk in association with PhIP, MDM, and MeIQx. CRC risk (21,344 cases) was increased by uptake of MeIQx (OR = 1.14; 95% CI: 1.04,1.25; p = 0.004), DiMeIQx (OR = 1.12; 95% CI: 1.02,1.22; p = 0.014) and MDM (OR = 1.12; 95% CI: 1.06,1.19; p < 0.001). No publication bias could be detected, whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity.