Abstract P3-12-07: Polymorphisms in the UDP-Glucuronosyltransferase 2B Gene Family and Risk of Breast Cancer in Women of African Descent

Background: The UDP-glucuronosyltransferase 2B (UGT2B) enzymes catalyze glucuronidation, which is an important clearance pathway of steroid hormones, and medications, and potential carcinogens. As steroid hormones play a central role in breast cancer development, genetic polymorphisms in the UGT2B gene family may affect breast cancer susceptibility. Methods: We evaluate two missense mutations in UGT2B15 (rs1902023, D85Y and rs4148269, K523T), one missense mutation in UGT2B7 (rs7439366, H268Y), and one single nucleotide polymorphism (SNP) 497 bp upstream to UGT2B4 (rs13129471) using pooled case-control studies of breast cancer, which included 1,287 cases and 851 controls. Cases and controls were enrolled in Nigeria, Barbados, and the US, and all are women of African ancestry. Results: All four SNPs followed Hardy-Weinberg equilibrium in each ethnicity group. We found the rs13129471 SNP was significantly associated with breast cancer risk after adjusting for ethnicity (P=0.003). Compared with homozygous genotype for the A-rs13129471 allele, the odds ratio for heterozygous genotype and homozygous genotype for the G-rs13129471 allele was 1.02 (95% CI: 0.81-1.28) and 1.50 (1.15-1.95), respectively. The association was stronger in Nigerian women (P=4x10- 5) and the corresponding odds ratio was 1.13 (95% CI: 0.85-1.49) and 2.39 (1.61-3.55). No significant association was found for the other three non-synonymous SNPs. Conclusion: Our results suggest that polymorphism in the UGT2B4 gene may be associated with breast cancer risk in women of African ancestry and the association may follow a recessive model. The finding needs to be confirmed in other populations. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-07.