Hereditary Susceptibility for Triple Negative Breast Cancer Associated with Western Sub-Saharan African Ancestry: Results from an International Surgical Breast Cancer Collaborative
Lisa A. Newman1, Joseph K. Oppong*2, Aisha S. Jibril*3, Jessica M. Bensenhaver*4, Baffour Awuah*2, Mahteme Bekele*3, Engida Abebe*3, Ishmael Kyei*2, Frances Aitpillah*2, S. David Nathanson*4, Brittany Jenkins*1, Lindsay F. Petersen*4, Erica Proctor*4, Kofi K. Gyan*1, Rick Kittles*5, Melissa B. Davis*1
1Weill Cornell Medicine, New York, NY;2Komfo Anokye Teaching Hospital, Kumasi, Ghana3Millenium Medical College St. Paul's Hospital, Addis Ababa, Ethiopia4Henry Ford Cancer Institute, Detroit, MI;5City of Hope Comprehensive Cancer Center, Los Angeles, CA
OBJECTIVE(S): Breast cancer mortality is higher in African American (AA) compared to White American (WA) women, and this disparity is partly-explained by a two-fold higher incidence of triple negative breast cancer (TNBC). The role of germline genetic factors in these differences is unclear.
METHODS: Database of 1024 breast cancers analyzed (233 AA; 433 WA; 263 West African/Ghanaian; 95 East African/Ethiopian); including 20% with matched saliva/DNA specimens and controls. All assembled through a surgically-maintained international biorepository. Genotyping was performed to quantify West African versus European ancestry and we also tested for associations between risk variants and tumor phenotype.
RESULTS: TNBC frequency was highest in Ghanaian and AA cases (51% and 33% respectively; p<0.02) and lowest in Ethiopian and WA cases (14% and 16% respectively; p<0.02). TNBC cases had significantly higher West African ancestry than non-TNBC (p<0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral genotype adopted under selective pressure as protection against malaria pathogens in West Africa) was strongly associated with cases (p=0.014), quantified West African Ancestry (p<0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 (a genetic variant associated with breast cancer risk) was significantly associated with Ghanaian cases (p=0.0248) compared to controls.
CONCLUSIONS: West African ancestry is strongly correlated with TNBC status, as well as germline variants related to breast cancer risk and metastatic virulence. Specifically, the Duffy-null allele (previously shown to be associated with pro-inflammatory chemokines implicated in tumor pathogenesis) accounted for TNBC risk in our cohort.
* By Invitation
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