Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort

Rachel Martini, Yalei Chen, Brittany D. Jenkins, Isra A. Elhussin, Esther Cheng, Syed A. Hoda, Paula S. Ginter, Jeffrey Hanover, Rozina B. Zeidan, Joseph K. Oppong, Ernest K. Adjei, Aisha Jibril, Dhananjay Chitale, Jessica M. Bensenhaver, Baffour Awuah, Mahteme Bekele, Engida Abebe, Ishmael Kyei, Frances S. Aitpillah, Michael O. AdinkuKwasi Ankomah, Ernest B. Osei-Bonsu, Saul David Nathansan, La Toya Jackson, Evelyn Jiagge, Lindsay F. Petersen, Erica Proctor, Petros Nikolinakos, Kofi K. Gyan, Clayton Yates, Rick Kittles, Lisa A. Newman, Melissa B. Davis

Research output: Contribution to journalArticlepeer-review

Abstract

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case–control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Original languageEnglish (US)
Article number9247
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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