Abstract 1450: Differences in expression levels of putative breast cancer risk genes in normal breast tissues between Black and White Americans

Abstract Background: Despite having a similar incidence of breast cancer, Black American women persistently endure higher mortality rates than their white counterparts. Reasons for this disparity are unclear. We evaluated possible racial differences in expression levels of putative breast cancer susceptibility genes identified in recent studies. Methods: Included in this analysis are 429 lincRNA or protein-coding risk genes identified in our recent transcriptome-wide association and fine-mapping studies using multi-ancestry data. In this study, The RNA sequencing data for these genes were derived from normal breast tissue samples obtained from 161 Black and 287 white participants recruited in the Susan G. Komen Biobank. To address potential batch effects, we used residuals after the probabilistic estimation of expression residuals correction, with standardized gene expression levels as input data after quantile and inverse rank normalization. Generalized linear regressions were used to investigate racial difference in gene expression levels. Models were adjusted for age, body mass index, and menopausal status. The significance threshold was set at 0.05 divided by the number of independent tests. Results: Out of the 429 genes evaluated in the study, 50 genes showed significant racial differences in expression levels at P < 4.54e-4 (0.05/110), the significant threshold after adjusting for multiple comparisons. Of them, 28 genes showed a higher expression level in Black than white participants. The top three genes with highest percent differences were GSTM1, PRSS45, and DIRC3. The GSTM1 gene showed a 65.86% higher expression level in Black samples (P=2.58e-9), followed by PRSS45 (percent difference = 37.75%, P = 9.84e-9) and DIRC3 (15.52%, 2.95e-11). On the other side, the top three genes with lowest percent difference were LRRC37A, ARL17A and LRRC37A2. Gene LRRC37A showed a 35.27% lower expression level in Black than white samples (P=2.22e-16), followed by gene ARL17A (-25.14%, 1.35e-15) and LRRC37A2 (-15.38%, 6.51e-13). Conclusion: We identified 50 genes showing racial differences in expression levels in breast normal tissues. Further research is needed to understand the reasons for these differences. Citation Format: Lili Liu, Guochong Jia, Jie Ping, Xingyi Guo, Ran Tao, Bingshan Li, Qiuyin Cai, Wei Zheng. Differences in expression levels of putative breast cancer risk genes in normal breast tissues between Black and White Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1450.