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Joint Effects between UDP-Glucuronosyltransferase 1A7 Genotype and Dietary Carcinogen Exposure on Risk of Colon Cancer

¹ Department of Public Health Sciences, Division of Epidemiology, University of California, Davis, California; ² Pharmacogenomics Laboratory, Oncology and Molecular Endocrinology Research Center, Centre Hospitalier de l'Université Laval and Faculty of Pharmacy Laval University, Québec, Canada; Departments of ³ Epidemiology and ⁴ Medicine; University of North Carolina, Chapel Hill, North Carolina; and ⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland

Requests for reprints: Chantal Guillemette, Canada Research Chair in Pharmacogenomics, Pharmacogenomics Laboratory, CHUQ Research Center, 2705 Boulevard Laurier, Quebec, Canada, G1V 4G2. E-mail: Chantal.Guillemette{at}crchul.ulaval.ca

The UDP-glucuronosyltransferase 1A7 (UGT1A7) gene is polymorphic and encodes an enzyme involved in the detoxification of heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH). Consumption of pan-fried and well-done meat are surrogates for HCA and PAH exposure and are possibly associated with colon cancer. We have evaluated whether UGT1A7 allelic variations are associated with colon cancer and whether UGT1A7 genotype modified associations among meat intake, exposure to HCAs and PAHs, and colon cancer in a population-based case-control study of African Americans (197 cases and 202 controls) and whites (203 cases and 210 controls). As part of a 150-item food frequency questionnaire, meat intake was assessed by cooking method and doneness and used to estimate individual HCA and PAH exposure. UGT1A7 alleles (UGT1A7*1, UGT1A7*2, UGT1A7*3, and UGT1A7*4) were measured and genotypes were categorized into predicted activity groups (high: *1/*1, *1/*2, *2/*2; intermediate: *1/*3, *1/*4, *2/*3; low: *3/*3, *3/*4, *4/*4). There was no association with UGT1A7 low versus high/intermediate genotype [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.7-1.8], regardless of race. Greater than additive joint effects were observed for UGT1A7 low genotype and HCA-related factors. For example, equal to or greater than the median daily intake of the HCA, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and having UGT1A7 low genotype was positively associated with colon cancer (OR, 2.4; 95% CI, 1.2-4.8), compared with less than the median daily intake and UGT1A7 high/intermediate genotypes. These data suggest that the associations among cooked meat–derived compound exposure, and colon cancer are modified by the UGT1A7 genotype.

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