Meat Intake, Heterocyclic Amine Exposure, and Metabolizing Enzyme Polymorphisms in Relation to Colorectal Polyp Risk

Abstract

Most colorectal cancers arise from adenomatous polyps or certain hyperplastic polyps. Only a few studies have investigated potential genetic modifiers of the associations between meat intake and polyp risk, and results are inconsistent. Using data from the Tennessee Colorectal Polyp Study, a large colonoscopy-based study, including 1,002 polyp cases (557 adenoma only, 250 hyperplastic polyp only, 195 both polyps) and 1,493 polyp-free patients, we evaluated the association of colorectal polyp risk with carcinogen exposure from meat and genetic polymorphisms in enzymes involved in heterocyclic amine (HCA) metabolism, including N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2), cytochrome P450 1A2 (CYP1A2), and aryl hydrocarbon receptor (AhR). Data on intake levels of meats by preparation methods, doneness preferences, and other lifestyle factors were obtained. Fourteen single nucleotide polymorphisms in the AhR, CYP1A2, NAT1, and NAT2 genes were evaluated. No clear association was found for any polymorphisms with polyp risk. However, apparent interactions were found for intake of meat and HCAs with AhR, NAT1, and NAT2 genotypes, and the interactions were statistically significant for the group with both adenomatous and hyperplastic polyps. Dose-response relationships with meat or HCA intake were found only among those with the AhR GA/AA (rs2066853) genotype, NAT1 rapid, or NAT2 rapid/intermediate acetylators but not among those with other genotypes of these genes. This doseresponse relationship was more evident among those with both AhR GA/AA and the NAT1 rapid acetylator than those without this genotype combination. These results provide strong evidence for a modifying effect of metabolizing genes on the association of meat intake and HCA exposure with colorectal polyp risk. (Cancer Epidemiol Biomarkers Prev 2008;17(2):320 -9)

Dietary Heterocyclic Amine Intake, NAT2 Genetic Polymorphism, and Colorectal Adenoma Risk: The Colorectal Adenoma Study in Tokyo

“…A few other studies found a statistically significant increased risk in rapid NAT2 acetylators with high HCA intake (22) or high processed meat intake (45) only or among individuals with the rapid phenotype for NAT2 and CYP1A2 and a preference for well-done or very well-done red meat (14). However, other studies failed to find such an association (46,47), and the P value for interaction between HCA intake and NAT2 phenotype in these (14,22,45) and other studies (46,47) was not significant. Our study has several strengths.…”

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

“…One article was subsequently excluded because it did not met the inclusion criteria since estimated the exposure to HCAs (low, intermediate and high) on the base of red meat source and preparation but not give their concentrations. Therefore, at the end of the selection process, 39 studies which met the inclusion criteria were enclosed in the systematic review and meta-analysis (Figure 1), 17 on CRA [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], 20 on CRC [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66], and 2 studies reported data on both CRA and CRC [67,68]. …”

“…Case-control studies were published between 2001 and 2015, 12 were population-based [31,32,35,37,39,40,[42][43][44]46,67,68] and 3 were hospital-based [30,33,45]. Twelve were conducted in the United States [30][31][32][33]35,37,39,40,42,44,67,68] and one each in Europe [43], Canada [45] and Japan [46].…”

“…The uptake of DiMeIQx was not reported in two studies [42,46] one of which reported data on MeIQ [46]. The total amount of HCAs was considered in three studies [42,46,67] while the MDM was reported in ten studies [30,32,[34][35][36][37][39][40][41]44,45]. The quality score for each study (see the on line Supplemental Table S2 and S3, for details of quality score calculation in case-control and cohort studies, respectively) is shown in the last right column of Supplemental Table S1.…”

“…The study of Shin et al was excluded from the calculation since the results reported the risk for a 10% increase of mutagen intake and it did not compare highest vs. the lowest values [37]. Overall, 15229 subjects with CRA were included in the meta-analysis.…”