Associations between Polymorphisms in Glucuronidation and Sulfation Enzymes and Mammographic Breast Density in Premenopausal Women in the United States

Abstract

Sex hormones are metabolized to less active compounds via (a) glucuronidation catalyzed by UDP-glucuronosyltransferases (UGT) and (b) sulfation catalyzed by sulfotransferases (SULT). Functional UGT and SULT polymorphisms can affect clearance of sex hormones, thereby influencing exposure in hormone-sensitive tissues, such as the breast. We assessed relationships between functional polymorphisms in the UGT and SULT genes and breast density in premenopausal women. One hundred seventy-five women ages 40 to 45 years, who had a screening mammogram taken within the previous year, provided a genomic DNA sample. Mammograms were digitized to obtain breast density measures. Using generalized linear regression, we assessed associations between percent breast density and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the SULT1A1(H213/H213) genotype had 16% lower percent breast density compared with women with the SULT1A1(R213/R213) genotype after controlling for ethnicity (P = 0.001). Breast density was 5% lower among women carrying at least one copy of the UGT1A1(TA7)-UGT1A3(R11)-UGT1A3(A47) haplotype compared with the UGT1A1(TA6)-UGT1A3(W11R)-UGT1A3(V47A) haplotype (P = 0.07). No associations were observed between polymorphisms in the UGT2B family or SULT1E1 and breast density. Polymorphisms in SULT1A1 and the UGT1A locus may influence percent breast density in premenopausal women.