Association of genetic polymorphisms in UGT1A1 with breast cancer and plasma hormone levels

UDP-glucuronosyltransferases (UGTs) catalyze the detoxification and the eli mination of a large number of endogenous and exogenous compounds in the liv er and extrahepatic tissues. One of the UGT1A family members, UGT1A1, is in volved in estradiol metabolism and, therefore, represents a candidate gene in breast carcinogenesis. A common insertion/deletion polymorphism in the T ATA-box of the promoter region of UGT1A1 results in decreased initiation of transcription. In a previous study, we found a positive association betwee n the UGT1A1 low-transcriptional alleles and premenopausal breast cancer ri sk in an African-American population. In the present study, we sought to de termine whether the low-transcription UGT1A1 promoter allele, UGT1A1*28 [A( TA)(7)TAA], was associated with increased breast cancer risk among primaril y Caucasian women in a nested case-control study within the Nurses' Health Study cohort. No significant association between the UGT1A1*28 [A(TA)(7)TAA ] allele and breast cancer was observed. Compared with women homozygous for the UGT1A1*1 [A(TA)(6)TAA] allele, the relative risk was 0.80 (confidence interval, 0.49-1.29) for women homozygous for the UGT1A1*28 allele, The eff ect of the UGT1A1 genotype on plasma hormone levels in postmenopausal women not using hormone replacement was also evaluated, and overall, no signific ant differences in hormone levels by genotypes were observed. When restrict ed to women who had at least one UGT1A1*28 allele and a body mass index at blood draw of > 27 kg/m(2), particularly in combination with the cytochrome p450c17 alpha genotype, estrone and estradiol levels tended to vary by UGT 1A1 genotypes, The results presented do not support a strong association be tween the UGT1A1 promoter polymorphism and the risk of breast cancer.