LAUSR

OBJECTIVE To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression. SUMMARY OF BACKGROUND DATA Higher rates of aggressive BC subtypes (TNBC) and worse overall BC survival are seen in black women [Hispanic (HB) and non-Hispanic (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown. METHODS Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I-IV non-Hispanic White (NHW), Hispanic White (HW), HB and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to ER+/HER2-, ER+/HER2+, and ER-/HER2+ disease. RESULTS Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC (OR 1.06,95%CI 1.001-1.126, P=0.046) as well as an inverse relationship between higher nSES and TNBC (OR 0.343,95%CI 0.151-0.781, P=0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR 1.049, 95%CI-0.987-1.116, P=0.120). Local ancestry analysis revealed nSES-independent enriched WA ancestral segment centered at chr2:42004914 (P=3.70×10-5) in patients with TNBC. CONCLUSIONS In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.