African Ancestry Associated Gene Expression Profiles in Triple Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent

Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.

PMID: 36121736 DOI: 10.1158/2159-8290.CD-22-0138


Other Contributors

Rachel Martini 1, Princesca Delpe 1, Timothy R Chu 2, Kanika Arora 3, Brittany Lord 1, Akanksha Verma 4, Deepa Bedi 5, Balasubramanyam Karanam 5, Isra Elhussin 6, Yalei Chen 7, Endale Gebregzabher 8, Joseph K Oppong 9, Ernest K Adjei 10, Aisha Jibril Suleiman 11, Baffour Awuah 10, Mahteme Bekele Muleta 11, Engida Abebe 8, Ishmael Kyei 12, Frances S Aitpillah 10, Michael O Adinku 13, Kwasi Ankomah 14, Ernest Baawuah Osei-Bonsu 15, Dhananjay A Chitale 7, Jessica M Bensenhaver 16, David S Nathanson 17, LaToya Jackson 7, Lindsay F Petersen 7, Erica Proctor 18, Brian Stonaker 1, Kofi K Gyan 1, Lee D Gibbs 19, Zarko Manojlovic 20, Rick A Kittles 21, Jason White 22, Clayton C Yates 6, Upender Manne 23, Kevin Gardner 24, Nigel Mongan 25, Esther Cheng 1, Paula Ginter 1, Syed Hoda 1, Olivier Elemento 26, Nicolas Robine 2, Andrea Sboner 27, John D Carpten 28, Lisa Newman 26, Melissa B Davis 27
Affiliations collapse
1Weill Cornell Medical College, New York City, NY, United States.
2New York Genome Center, New York, NY, United States.
3Memorial Sloan Kettering Cancer Center, New York, NY, United States.
4Weill Cornell Medicine, United States.
5Tuskegee University, United States.
6Tuskegee University, Tuskegee, AL, United States.
7Henry Ford Health System, Detroit, MI, United States.
8St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia.
9Komgo Anoyke Teaching Hospital, Ghana.
10Komfo Anoyke Teaching Hospital, Kumasi, Ghana.
11St Paul’s Millennium Medical College, Addis Ababa, Ethiopia.
12Kwame Nrumah University of Science and Technology, Kumasi, Ghana.
13Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
14Komfo Anokye Teaching Hospital, Kumasi, Ghana.
15Komfo Anokye Teaching Hospital, Kumasi, Ashanti Region, Ghana.
16Henry Ford Hospital, United States.
17Henry Ford Health, Detroit, United States.
18Northside Hospital, Atlanta, GA, United States.
19Keck School of Medicine of University of Southern California, Los Angeles, California, United States.
20Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
21Morehouse School of Medicine, Atlanta, GA, United States.
22Tuskegee University, Tuskegee, Albam, United States.
23University of Alabama at Birmingham, BIRMINGHAM, Alabama, United States.
24Columbia University Medical Center, New York, New York, United States.
25University of Nottingham, Nottingham, United Kingdom.
26Weill Cornell Medicine, New York, New York, United States.
27Weill Cornell Medicine, New York, NY, United States.
28University of Southern California, Los Angeles, CA, United States.