Prevalence of the UGT1A1*28 promoter polymorphism and breast cancer risk among African American women in Memphis, TN.

Inherited variations in UDP-glucuronosyltransferase 1A1 (UGT1A1) are associated with an increased breast cancer risk in women of African ancestry. The promoter polymorphism is characterized by the presence of 7 TA repeats in the TATA box sequence and results in reduced UGT1A1 gene expression and enzymatic activity. In this study, we investigated associations between the polymorphism and breast cancer risk among African American (AA) women in Memphis, Tennessee, a city with increased breast cancer mortality rates among AA women. Saliva was collected from 352 AA women, including breast cancer cases (n=82) and controls (n=270) between June 2016 to June 2017. DNA was isolated and sequenced for the polymorphism. The odds ratio for cases with the low activity alleles (TA)7/8 repeat genotypes versus 5/5, 5/6, and 6/6 genotypes was 1.46 [95% CI, 0.65-3.31; P = 0.36] in premenopausal women and 1.10 (95% CI, 0.52-2.38; P = 0.79) in postmenopausal women. Further analysis of TCGA RNA-seq data showed that UGT1A1 mRNA was significantly lower among estrogen receptor (ER)-negative breast cancers from AA as compared to non-Hispanic white women with ER-negative breast cancer. Larger epidemiological studies are needed to determine the functional consequence of the polymorphism on breast cancer risk in AA women.