Smith Alana, Cropp Cheryl D, Vidal Gregory, Pritchard Elizabeth, Cordero Jennifer, Simpson Claire, Starlard-Davenport Athena
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Integrated Cancer Genomics Division, Translational Genomics Research Institute (TGen), Phoenix, AZ, 85004, USA.
Cancer Health Disparities. 2019 Aug 19;3:e1-e12. doi: 10.9777/chd.2019.1015.
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.
尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）的遗传变异与非洲裔女性患乳腺癌风险增加相关。启动子多态性的特征是TATA盒序列中存在7个TA重复序列，导致UGT1A1基因表达和酶活性降低。在本研究中，我们调查了田纳西州孟菲斯市非裔美国（AA）女性中该多态性与乳腺癌风险之间的关联，孟菲斯市AA女性的乳腺癌死亡率有所上升。2016年6月至2017年6月期间，从352名AA女性中收集唾液，包括乳腺癌病例（n = 82）和对照（n = 270）。分离DNA并对该多态性进行测序。绝经前女性中，低活性等位基因（TA）7/8重复基因型与5/5、5/6和6/6基因型病例的比值比为1.46 [95% CI，0.65 - 3.31；P = 0.36]，绝经后女性中为1.10（95% CI，0.52 - 2.38；P = 0.79）。对TCGA RNA测序数据的进一步分析表明，与非西班牙裔白人女性的雌激素受体（ER）阴性乳腺癌相比，AA女性的ER阴性乳腺癌中UGT1A1 mRNA显著更低。需要更大规模的流行病学研究来确定该多态性对AA女性乳腺癌风险的功能影响。
