Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism–related genes on the association of HCA intake with the risk of colorectal adenomas
- 346 Downloads
Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC.
A case–control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis.
CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p Interaction > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance.
HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.
KeywordsColorectal adenoma Genetic polymorphisms Phenotypes Heterocyclic aromatic amines
This study was granted by the Kurt-Eberhard-Bode Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
- 14.Tiemersma EW, Voskuil DW, Bunschoten A, Hogendoorn EA, Witteman BJ, Nagengast FM, Glatt H, Kok FJ, Kampman E (2004) Risk of colorectal adenomas in relation to meat consumption, meat preparation, and genetic susceptibility in a Dutch population. Cancer Causes Control 15(3):225–236. doi: 10.1023/B:CACO.0000024263.44973.92 PubMedCrossRefGoogle Scholar
- 19.Shin A, Shrubsole MJ, Rice JM, Cai Q, Doll MA, Long J, Smalley WE, Shyr Y, Sinha R, Ness RM, Hein DW, Zheng W (2008) Meat intake, heterocyclic amine exposure, and metabolizing enzyme polymorphisms in relation to colorectal polyp risk. Cancer Epidemiol Biomarkers Prev 17(2):320–329. doi: 10.1158/1055-9965.EPI-07-0615 PubMedCrossRefGoogle Scholar
- 23.Wang H, Yamamoto JF, Caberto C, Saltzman B, Decker R, Vogt TM, Yokochi L, Chanock S, Wilkens LR, Le Marchand L (2010) Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia. Carcinogenesis 32(2):203–209. doi: 10.1093/carcin/bgq237 PubMedCrossRefGoogle Scholar
- 25.Sinha R, Rothman N, Brown ED, Mark SD, Hoover RN, Caporaso NE, Levander OA, Knize MG, Lang NP, Kadlubar FF (1994) Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans. Cancer Res 54(23):6154–6159PubMedGoogle Scholar
- 27.Eichholzer M, Rohrmann S, Barbir A, Hermann S, Teucher B, Kaaks R, Linseisen J (2012) Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk. Int J Mol Epidemiol Gen (accepted)Google Scholar
- 28.Ferrucci LM, Cross AJ, Gunter MJ, Ahn J, Mayne ST, Ma X, Chanock SJ, Yeager M, Graubard BI, Berndt SI, Huang WY, Hayes RB, Sinha R (2010) Xenobiotic metabolizing genes, meat-related exposures, and risk of advanced colorectal adenoma. World Rev Nutr Diet 101:34–45. doi: 10.1159/000314509 PubMedCrossRefGoogle Scholar
- 30.Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, Charrondiere UR, Hemon B, Casagrande C, Vignat J, Overvad K, Tjonneland A, Clavel-Chapelon F, Thiebaut A, Wahrendorf J, Boeing H, Trichopoulos D, Trichopoulou A, Vineis P, Palli D, Bueno-De-Mesquita HB, Peeters PH, Lund E, Engeset D, Gonzalez CA, Barricarte A, Berglund G, Hallmans G, Day NE, Key TJ, Kaaks R, Saracci R (2002) European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5(6B):1113–1124. doi: 10.1079/PHN2002394 PubMedCrossRefGoogle Scholar
- 31.Bohlscheid-Thomas S, Hoting I, Boeing H, Wahrendorf J (1997) Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the German part of the EPIC project. European Prospective Investigation into Cancer and Nutrition. Int J Epidemiol 26(Suppl 1):S59–S70PubMedCrossRefGoogle Scholar
- 34.Sinha R, Rothman N, Salmon CP, Knize MG, Brown ED, Swanson CA, Rhodes D, Rossi S, Felton JS, Levander OA (1998) Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings. Food Chem Toxicol 36(4):279–287PubMedCrossRefGoogle Scholar
- 36.Butler LM, Duguay Y, Millikan RC, Sinha R, Gagne JF, Sandler RS, Guillemette C (2005) Joint effects between UDP-glucuronosyltransferase 1A7 genotype and dietary carcinogen exposure on risk of colon cancer. Cancer Epidemiol Biomarkers Prev 14(7):1626–1632. doi: 10.1158/1055-9965.EPI-04-0682 PubMedCrossRefGoogle Scholar
- 42.Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey AB, Harper PA (2008) Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 17(11):3098–3107. doi: 10.1158/1055-9965.EPI-08-0341 PubMedCrossRefGoogle Scholar