Hereditary Susceptibility for Triple Negative Breast Cancer Associated with Western Sub-Saharan African Ancestry: Results from an International Surgical Breast Cancer Collaborative

Lisa A. Newman, Brittany Jenkins, Yalei Chen, Joseph K. Oppong, Ernest Adjei, Aisha S. Jibril, Syed Hoda, Esther Cheng, Dhananjay Chitale, Jessica M. Bensenhaver, Baffour Awuah, Mahteme Bekele, Engida Abebe, Ishmael Kyei, Frances Aitpillah, Michael Adinku, Saul David Nathanson, Latoya Jackson, Evelyn Jiagge, Sofia MerajverLindsay F. Petersen, Erica Proctor, Kofi K. Gyan, Rachel Martini, Rick Kittles, Melissa B. Davis

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Objective:To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations.Background:Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence.Methods:We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC.Results:TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P < 0.0001), quantified West African Ancestry (P < 0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant.Conclusions:West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

Original languageEnglish (US)
Pages (from-to)484-492
Number of pages9
JournalAnnals of surgery
Volume270
Issue number3
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

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Keywords

  • African ancestry
  • disparities
  • triple negative breast cancer

ASJC Scopus subject areas

  • Surgery

Cite this

Newman, L. A., Jenkins, B., Chen, Y., Oppong, J. K., Adjei, E., Jibril, A. S., Hoda, S., Cheng, E., Chitale, D., Bensenhaver, J. M., Awuah, B., Bekele, M., Abebe, E., Kyei, I., Aitpillah, F., Adinku, M., Nathanson, S. D., Jackson, L., Jiagge, E., ... Davis, M. B. (2019). Hereditary Susceptibility for Triple Negative Breast Cancer Associated with Western Sub-Saharan African Ancestry: Results from an International Surgical Breast Cancer Collaborative. Annals of surgery, 270(3), 484-492. https://doi.org/10.1097/SLA.0000000000003459