Exposure to heterocyclic amines, benzo(a)pyrene, and mutagenicity from meat intake characterized by cooking methods and doneness, genetic susceptibility at the N-acetyltransferase 1 and 2 loci, and association with colon cancer in a population-based study

The association between colon cancer and meat intake was examined in this dissertation. Meat intake was categorized according to level of doneness, cooking method, and estimated dietary heterocyclic amine (HCA), polycyclic aromatic hydrocarbon (PAH), and meat-derived mutagenicity content. Differences were assessed in these associations according to N-acetyltransferase 1 (NAT1) and 2 (NAT2) genotypes. Data were collected as part of a population-based case-control study of invasive colon cancer in African-Americans and whites. Cases and controls were selected from 33-counties in North Carolina, with a final study size of 290 African-American cases, 352 white cases, 433 African-American controls, 616 white controls. Dietary intake was measured using a food frequency questionnaire, and photographs were used to assess four levels of meat doneness. NAT1 (*3, *4, *10, *11) and NAT2 (*4, *5, *6, *7, *14) alleles were determined using PCR-based methods. Intake of five selected red meats comparing the fifth to first quintile was positively associated with colon cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.3, 3.21. Associations for cooking method were strongest for pan fried red meat, with an odds ratio of 2.1 (95% CI = 1.4, 3.0). For all HCAs, the strongest association was reported for DiMeIQx (OR = 1.8; 95% CI = 1.1, 3.1), comparing fifth to first quintile. There was no association with colon cancer for NAT1 or NAT2 genotype, overall, or among racial groups. Positive interactions were observed as greater than the additive and multiplicative null values for pan fried chicken intake and NAT1; ORs for fifth versus first quintile of intake were 0.8 (95% CI = 0.4, 1.4) and 2.2 (95% CI = 1.3, 3.7), among individuals with NAT1-non*10 and NAT1 *10 genotypes, respectively. Similar departures from multiplicativity were observed for DiMeIQx exposure and NAT1; ORs for fifth versus first quintile of exposure were 1.0 (95% CI = 0.5, 2.2) and 4.7 (95% CI = 1.7,13.0), among individuals with NAT1-non*10 and NAT1*10 genotypes, respectively. Positive interaction was also observed on the multiplicative scale for pan fried red meat intake (OR = 1.6; 95% CI = 0.8, 3.0 among NAT2-slow, and OR = 2.6; 95% CI = 1.4, 4.8 among NAT2-rapid/intermediate). Overall, these findings support previously reported modest associations between red meat intake and colon cancer. The stronger positive interaction with “high activity” NAT genotypes and pan fried meat, as well as DiMeIQx are consistent with the hypothesis that HCAs may an etiologically relevant compound of meat intake.