| Title | Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Newman LA, Jenkins B, Chen Y, Oppong JK, Adjei E, Jibril AS, Hoda S, Cheng E, Chitale D, Bensenhaver JM, Awuah B, Bekele M, Abebe E, Kyei I, Aitpillah F, Adinku M, Nathanson SDavid, Jackson LT, Jiagge E, Merajver S, Petersen LF, Proctor E, Gyan KK, Martini R, Kittles R, Davis MB |
| Journal | Ann Surg |
| Volume | 270 |
| Issue | 3 |
| Pagination | 484-492 |
| Date Published | 2019 09 |
| ISSN | 1528-1140 |
| Keywords | Adult, Africa South of the Sahara, African Americans, Aged, Case-Control Studies, Databases, Factual, Disease Susceptibility, Female, Germ-Line Mutation, Ghana, Humans, Incidence, Internationality, Middle Aged, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Risk Assessment, Triple Negative Breast Neoplasms, United States |
| 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. |
| DOI | 10.1097/SLA.0000000000003459 |
| Alternate Journal | Ann Surg |
| PubMed ID | 31356281 |
| Grant List | L60 MD002419 / MD / NIMHD NIH HHS / United States L60 MD011128 / MD / NIMHD NIH HHS / United States |
Related Faculty:
Syed Hoda, M.D.