title: Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and breast cancer risk in Africans.
abstract: The UDP-glucuronosylatransferase 1A1 (UGT1A1) gene is involved in the metabolism of estrogen and detoxification of potential carcinogens. The number of TA repeats in the promoter region of UGT1A1 has been linked to breast cancer risk, but results varied by race. We performed a comprehensive assessment of genetic polymorphisms in the UGT1A1 gene, and examined these polymorphisms and TA repeats in relation to breast cancer risk in a case-control study in Nigeria. 512 breast cancer cases and 226 community controls were genotyped for UGT1A1. Compared with high-activity TA repeat genotypes, the odds ratios (OR) for low-activity and moderate-activity genotypes were 0.47 (95% confidence interval CI, 0.26-0.83) and 0.64 (95% CI, 0.39-1.06), respectively, in premenopausal women (P = 0.009 for trend), but no association was observed in postmenopausal women (P = 0.24). The effect of TA repeats was also differentiated by age: the OR was 0.39 (95% CI 0.21-0.71) for low-activity genotypes and 0.58 (95% CI 0.33-1.00) for moderate-activity genotypes in women <45 years old (P = 0.002 for trend), but no association was observed in women >or=45 years old (P = 0.15). Haplotype analysis showed that UGT1A1 haplotypes were highly diverse with blocked structures. We found a specific haplotype in block 2 that was significantly associated with a 2.1-fold elevated risk (95% CI 1.05-4.39; P = 0.04). In contrast with previous studies, we found low-activity TA repeat alleles were protective against breast cancer among premenopausal indigenous Africans, suggesting that the role of UGT1A1 in breast cancer development may vary by population, presumably due to different environmental and genetic modifier effects.
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, IL, USA.
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Clement A
authors.initials: CA
authors.lastname: Adebamowo
authors.forename: Temidayo O
authors.initials: TO
authors.lastname: Ogundiran
authors.forename: Effiong E
authors.initials: EE
authors.lastname: Akang
authors.forename: Oladapo
authors.initials: O
authors.lastname: Campbell
authors.forename: Adeniyi
authors.initials: A
authors.lastname: Adenipekun
authors.forename: Qun
authors.initials: Q
authors.lastname: Niu
authors.forename: Lise
authors.initials: L
authors.lastname: Sveen
authors.forename: James D
authors.initials: JD
authors.lastname: Fackenthal
authors.forename: Donna Lee
authors.initials: DL
authors.lastname: Fackenthal
authors.forename: Soma
authors.initials: S
authors.lastname: Das
authors.forename: Nancy
authors.initials: N
authors.lastname: Cox
authors.forename: Anna
authors.initials: A
authors.lastname: Di Rienzo
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
mesh_terms: D000328:Adult; D000349:Africa; D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme