FOXA1 genetic alterations in Whites versus Blacks/African Americans in Breast and Prostate Cancer

Forkhead box A1 (FOXA1) is a pioneer factor for the nuclear hormone receptors: estrogen receptor and androgen receptor. FOXA1 plays a major role inducing endocrine resistance in breast cancer (BC) and prostate cancer (PC), the two most prevalent cancers in the United States. In this study, we investigated FOXA1 gene alterations across different race and ethnicity using the TCGA PanCan Atlas dataset for BC and PC patients. The BC and PC dataset included 1084 and 494 patient samples, respectively, profiled for copy number alterations (CNA), gene expression, and mutations. In the BC dataset, the incidence of FOXA1 alterations was 16/1070 (1.5%) CNA 24/1082 (2.2%) high mRNA expression, and 31/1066 (2.9%) mutations. Only amplifications were found within the BC patients. In the PC dataset, there were 15/489 (3.1%) CNA, 16/493 (3.2%) high mRNA expression, and 28/494 (5.7%) mutations reported in FOXA1. Deep deletion was found in one of the PC patients while the rest had amplifications. Due to insufficient numbers of Hispanic patients in the datasets, we compared the incidence of various FOXA1 alterations in White vs. Black/AA population using Fisher’s exact test. Only FOXA1 mutation rate was significantly higher (p =0.03) in Blacks/AA (2/7, 28.6%) compared to Whites (5/147, 3.4%) in PC, but not in the BC dataset. Additional studies with larger datasets that include the race and ethnicity information from diverse group of patients as well as tumor molecular subtyping are also needed for the assessment of the mechanism of health disparity in BC and PC in minority population in the United States. This project was completed with contributions from Xiaoyong Fu and Rachel Schiff from Baylor College of Medicine.