Year: 2021
Type: article
Study design: Observational Study
Abstract: Background: Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women. Methods: We investigated associations between pathogenic variants (PV) in 34 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 the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women. Results: The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03–46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17–15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15–138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72–6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P < 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks. Conclusions: We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries. Impact: These findings have direct relevance for breast cancer genetic counseling for women in West Africa.
Authors: Thomas U. Ahearn, Parichoy Pal Choudhury, Andriy Derkach, Beatrice Wiafe-Addai, Baffour Awuah, Joel Yarney, Lawrence Edusei, Nicholas Titiloye, Ernest Adjei, Verna Vanderpuye, Francis Aitpillah, Florence Dedey, Joseph Oppong, Ernest Baawuah Osei-Bonsu, Máire A. Duggan, Louise A. Brinton, Jamie Allen, Craig Luccarini, Caroline Baynes, Sara Carvalho, Alison M. Dunning, Brittny C. Davis Lynn, Stephen J. Chanock, Belynda D. Hicks, Meredith Yeager, Nilanjan Chatterjee, Richard Biritwum, Joe Nat Clegg-Lamptey, Kofi Nyarko, Seth Wiafe, Daniel Ansong, Douglas F. Easton, Jonine D. Figueroa, Montserrat Garcia-Closas
Institutions: National Cancer Institute, Division of Cancer Epidemiology and Genetics, Memorial Sloan Kettering Cancer Center, Komfo Anokye Teaching Hospital, Korle Bu Teaching Hospital, University of Calgary, University of Cambridge, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States), Johns Hopkins University, Johns Hopkins Medicine, University of Ghana, Loma Linda University, Edinburgh Cancer Research, University of Edinburgh
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: G2004299919, G2376452410, Breast Cancer Risk after Diagnostic Gene Sequencing (BRIDGES), G434337789, Determination of the prevalence breast cancer predisposition genes in South East Asian women and development of an Asian polygenic risk assessment tool, G6374948078, G6871046858, Cancer Center Support Grant
OpenAlex ID: W4282930103