Oncologic Anthropology: An Interdisciplinary Approach to Understanding the Association Between Genetically Defined African Ancestry and Susceptibility for Triple Negative Breast Cancer

This review aims to present contemporary research regarding the association between genetic/germline African ancestry and risk of triple negative breast cancer (TNBC). TNBC is more common in African American compared to White American women and contributes to breast cancer outcome disparities. Variation in the frequency of TNBC across different regions of Africa suggests that population migration (the African diaspora) and the genetics of African ancestry contribute to this epidemiology. Our group has coined the nomenclature “oncologic anthropology” to describe the study of these global breast cancer patterns. Cancer-associated founder mutations which have been identified for most ancestral heritage groups represent examples of oncologic anthropology. Herein, we present the expanding body of research related to the Duffy antigen receptor for chemokines (DARC)/atypical chemokine receptor 1 (ACKR1) and its association with cancer-related cytokines as a factor in the etiology of differences in breast cancer burden. DARC/ACKR1 expression on erythrocytes is also widely known as the “Duffy blood group,” and the genotype resulting in its absence (Duffy-null) was under strong evolutionary selection pressure in western, sub-Saharan Africa several thousand years ago because of the protection afforded by this phenotype against malaria pathogens. The Duffy-null allele is therefore nearly fixed among populations in this region of Africa, and it has varying prevalence among populations with admixed western sub-Saharan African ancestry (such as African Americans and East Africans). Recently characterized associations between an African ancestry-specific DARC/ACKR1 variant, breast tumor DARC/ACKR1 expression, and DARC/ACKR1 influence on cancer-associated chemokines indicate that this gene is important in understanding disease progression as well as breast cancer disparities.