title: Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancer.
abstract: Uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) is the key hepatic detoxification enzyme involved in the biotransformation of many carcinogens implicated in the development of colon, breast, and prostate cancers in humans. A polymorphism in the UGT1A1 promoter containing a TA-repeat element [(TA)5-8TAA] is involved in the modulation of UGT1A1 transcriptional activity. The wild-type activity is associated with the (TA)6TAA allele (UGT1A1*1), whereas UGT1A1 expression decreases with the increase of the TA-repeat number. We hypothesize that the low-activity allele UGT1A1*28 with seven TA repeats is associated with a higher risk for colorectal cancer. Our study involved 168 patients with histopathologically confirmed sporadic colorectal cancer and a control group of 96 individuals with no personal history of colorectal cancer. We detected a higher frequency of UGT1A1*28 than the wild-type UGT1A1*1 allele in colorectal cancer patients as compared with that of controls (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.07-2.26, P = 0.021). The frequency of genotypes containing the UGT1A1*28 allele in the homozygous or heterozygous state was significantly higher than the frequency of the wild-type UGT1A1*1/*1 genotype in colorectal cancer patients as compared with controls (OR = 2.0, 95% CI = 1.19-3.34, P = 0.007). Our results indicate that the UGT1A1*28 allele is a risk factor for colorectal cancer in the Macedonian male population, whereas no significant risk was detected among women.
authors.affiliation: Faculty of Pharmacy, Saints Cyril and Methodius University, Skopje, Republic of Macedonia.
authors.forename: Marija Hiljadnikova
authors.initials: MH
authors.lastname: Bajro
authors.forename: Toni
authors.initials: T
authors.lastname: Josifovski
authors.forename: Milco
authors.initials: M
authors.lastname: Panovski
authors.forename: Nikola
authors.initials: N
authors.lastname: Jankulovski
authors.forename: Aleksandra Kapedanovska
authors.initials: AK
authors.lastname: Nestorovska
authors.forename: Nadica
authors.initials: N
authors.lastname: Matevska
authors.forename: Natalija
authors.initials: N
authors.lastname: Petrusevska
authors.forename: Aleksandar J
authors.initials: AJ
authors.lastname: Dimovski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006115:Greece; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme