Abstract A24: Triple-negative breast Cancer risk: Ancestry and immune response

Abstract

Abstract Background: Blacks in the U.S. have the worst breast cancer survival outcomes of any racial/ethnic group in the nation. However, blacks are not a monolithic group but are comprised of several ethnic groups. One such group in particular is the Sea Island or Gullah population of coastal South Carolina, North Carolina, Georgia, and Florida, whose ancestors came from coastal rice-growing areas of Africa. Sea Islanders (SI) have the lowest rates of European (non-Hispanic white) genetic admixture of any U.S. blacks, and are thus a special population who provide a rare opportunity to investigate genetic contributions to the profound ancestrally linked disparities in BC. Purpose: The purpose of this study was to identify, for the first time, frequencies of selected single nucleotide polymorphisms (SNPs) associated with triple-negative breast cancer (TNBC) in these three non-Hispanic population groups: whites, African Americans without Sea Island ancestry (AA), and African Americans with Sea Island ancestry (SI). Methods: Saliva samples were obtained using a mailed kit from a sample of 90 women in SC who had been diagnosed with TNBC in the past 1.5 years, recruited from the three population groups (30 women per group). Four SNPs on the 19p13 locus of BRCA 1 (rs8170, rs4808611, rs2363956, and rs3745185) were evaluated. Results: The percentage of TNBC cases was 6.7% among whites, 4.2% among SI blacks, and 22% among non-SI blacks. After controlling for TNBC status, similar allele frequencies for each SNP were seen in whites and SI blacks, compared to non-SI blacks (p<0.01). The less genetically admixed groups (SI and whites) had a lower percentage of triple-negative breast cancer (AA vs. whites, p=0.02; AA vs. SI, p=0.03; whites vs SI: p=0.99) Discussion: The prevalence of triple-negative breast cancer is significantly higher in African American women, and at younger ages, than in white women. Findings by Mukhtar et al. (2011) implicate immune function in the development of this aggressive breast cancer, as higher proliferating cellular nuclear antigen counts and tumor-associated macrophages were associated with hormone receptor-negative tumors and non-white ethnicity. Human populations differ in their transcriptional responses to immune challenges, and immune-responsive regulatory variants have participated in human adaptation by positive selection. Regulatory variants affecting steady-state gene expression and transcriptional responsiveness to immune challenges, particularly those that were viral related, may have been preferentially introduced into African genomes through admixture with Europeans, which may have conferred a natural selection disadvantage to modern blacks without SI ancestry. Such a natural selection disadvantage may mean that different immunologic therapeutic approaches are required for blacks with cancer than for whites with cancer, particularly for more aggressive disease. Citation Format: Marvella E. Ford, Erika T. Brown, David P. Turner, Victoria J. Findlay, Nestor F. Esnaola, Anthony J. Alberg, Susan Bolick, Deborah Hurley, Rita Kramer, Judith D. Salley, Joan E. Cunningham. Triple-negative breast Cancer risk: Ancestry and immune response [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A24.