• Annals of surgery · Sep 2019

    Comparative Study

    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 Merajver, Lindsay F Petersen, Erica Proctor, Kofi K Gyan, Rachel Martini, Rick Kittles, and Melissa B Davis.
    • Weill Cornell Medicine, New York, NY.
    • Ann. Surg. 2019 Sep 1; 270 (3): 484492484-492.

    ObjectiveTo investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations.BackgroundBreast 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.MethodsWe 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.ResultsTNBC 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.ConclusionsWest 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.

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