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

Abstract

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,4,

Influence of Nonsynonymous Polymorphisms of UGT1A8 and UGT2B7 Metabolizing Enzymes on the Formation of Phenolic and Acyl Glucuronides of Mycophenolic Acid

“…DNA samples from 254 healthy unrelated Caucasian subjects were obtained from the Quebec Family Study for UGT1A8 single-nucleotide polymorphism (SNP) genotyping (Simonen et al, 2002). Additional random DNA samples from African-American subjects (n ϭ 41) used in a previous study were sequenced (Butler et al, 2005). Subject identifiers for these samples had been removed before their reception in our laboratory.…”

Uridine diphosphoglucuronosyltransferase pharmacogenetics and cancer

“…The report found no association between UGT1A7 low-versus high-activity genotype and CRC incidence. However, UGT1A7 variants had an additive effect with HCA exposure; thus, the risk for colon cancer was significantly associated with low UGT1A7 activity plus increased HCA exposure (Butler et al, 2005).…”

Characterizing the Effects of Common UDP Glucuronosyltransferase (UGT) 1A6 and UGT1A1 Polymorphisms oncis-andtrans-Resveratrol Glucuronidation

“…Interethnic differences in frequency of UGT polymorphisms are known to exist, confounded by populations with variable exposures to dietary phytochemicals known to be conjugated by various UGTs. With respect to chemoprevention, several epidemiologic studies have attempted to correlate colorectal cancer risk with various UGT polymorphisms and exposure to dietary carcinogens (Fang and Lazarus, 2004;Butler et al, 2005;Girard et al, 2005). However, these polymorphic UGTs are not limited to simply inactivating carcinogens but also play a role in inactivating compounds such as chemopreventive nonsteroidal anti-inflammatory drugs and phytochemicals (Bigler et al, 2001;Chan et al, 2005).…”