Abstract 5601: The role of UDP-Glucuronosyltransferases in human breast cancers

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Reports of an unanticipated increase in cancer risk following exposure to tamoxifen and estrogen-containing drugs suggest that long-term consequences of genetic variations in drug metabolism may need to be elucidated more thoroughly during product development. Variations in UGTs that metabolize these drugs may result in reduced drug efficacy in estrogen target tissues, such as the breast in women. In this study, we characterized the expression of UGTs in normal (n = 31) and malignant (n = 17) human breast tissues from African American and Caucasian women. Several UGT isoforms, including UGT1A1, -1A4, -1A10, and -2B7 mRNA were down-regulated in malignant human breast specimens compared to normal breast specimens as determined by real-time PCR. In addition, UGT1A4, which is the major UGT responsible for conjugating tamoxifen, was genotyped for the UGT1A424Pro/48Val and UGT1A424Thr/48Leu variant. However, the UGT1A448Val variant was not significant prevalent within these population of samples. It is anticipated that this study will provide novel information on the role of UGTs in the breast and provide insight as to how alterations in UGT expression will impact the clearance of estrogens and tamoxifen in women. It is anticipated that this study will be instrumental in predicting tamoxifen toxicity and estrogen carcinogenicity in women with a non-functional UGT variant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5601. doi:10.1158/1538-7445.AM2011-5601