Breast Cancer Risk in Women from Ghana Carrying Rare Germline Pathogenic Mutations: A Resource for Genetic Counseling of West African Women

Background: Breast cancer risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women, with limited data for women in West African.   Methods: We investigated associations between pathogenic variants in 34 putative susceptibility genes with breast cancer risk in 871 cases (307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown) and 1,563 controls in a population-based study in Ghana, and estimated lifetime risk for mutation carriers in the general population. We compared results to those for European, Asian and African-American women. Findings: The frequency of pathogenic mutations in nine breast cancer genes (BRCA1, BRCA2, PALB2, TP53, ATM, BARD1, CHEK2, RAD51C, RAD52D) was 8·38% in cases and 1·22% in controls from GBHS. Mutations in BRCA1, BRCA2, PALB2, and TP53 were significantly associated with breast cancer risk at P<0·05, and relative risk estimates for these genes and moderate-risk genes (ATM, BARD1, CHEK2, RAD51C, RAD52D) were of similar magnitude to other populations. The estimated lifetime risks in Ghana for mutation carriers in BRCA1, BRCA2 and PALB2 and moderate risk genes were 18·4%, 9·8%, 22·4% and 3·1%, respectively, which are lower than in Western populations with higher baseline risks. Interpretation: We confirmed associations between pathogenic mutations and breast cancer risk in Ghanaian women and provide population-based absolute risk estimates that could inform counseling in Ghana and other West African countries. Funding: This project was funded with intramural funds from the National Cancer Institute, National Institutes of Health. Declaration of Interests: Authors have no conflicts of interest to declare. Ethics Approval Statement: The study was approved by the Special Studies Institutional Review Board of the National Cancer Institute (Rockville, MD), the Ghana Health Service Ethical Review Committee and institutional review boards at the Noguchi Memorial Institute for Medical Research (Accra, Ghana), the Kwame Nkrumah University of Science and Technology (Kumasi, Ghana), the School of Medical Sciences at Komfo Anokye Teaching Hospital (Kumasi, Ghana) and Westat (Rockville, MD). All participants provided written informed consent.