Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative. Academic Article uri icon

Overview

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.

authors

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

publication date

  • September 1, 2019

Research

keywords

  • Black or African American
  • Disease Susceptibility
  • Germ-Line Mutation
  • Receptor, ErbB-2
  • Triple Negative Breast Neoplasms

Identity

Scopus Document Identifier

  • 85070952356

Digital Object Identifier (DOI)

  • 10.1097/SLA.0000000000003459

PubMed ID

  • 31356281

Additional Document Info

volume

  • 270

issue

  • 3