Breast Cancer Risk in Women from Ghana Carrying Rare Germline Pathogenic Mutations

Author:

Ahearn Thomas U.1ORCID,Choudhury Parichoy Pal1,Derkach Andriy2ORCID,Wiafe-Addai Beatrice3,Awuah Baffour4,Yarney Joel5,Edusei Lawrence5,Titiloye Nicholas4ORCID,Adjei Ernest4ORCID,Vanderpuye Verna5,Aitpillah Francis4ORCID,Dedey Florence5ORCID,Oppong Joseph4ORCID,Osei-Bonsu Ernest Baawuah4ORCID,Duggan Máire A.6ORCID,Brinton Louise A.1ORCID,Allen Jamie7ORCID,Luccarini Craig8,Baynes Caroline8,Carvalho Sara7ORCID,Dunning Alison M.8ORCID,Davis Lynn Brittny C.1,Chanock Stephen J.1ORCID,Hicks Belynda D.9ORCID,Yeager Meredith9,Chatterjee Nilanjan1011,Biritwum Richard12ORCID,Clegg-Lamptey Joe Nat5ORCID,Nyarko Kofi12,Wiafe Seth13ORCID,Ansong Daniel4ORCID,Easton Douglas F.78,Figueroa Jonine D.14,Garcia-Closas Montserrat1ORCID

Affiliation:

1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.

2. 2Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

3. 3Peace and Love Hospital, Kumasi, Ghana.

4. 4Komfo Anokye Teaching Hospital, Kumasi, Ghana.

5. 5Korle Bu Teaching Hospital, Accra, Ghana.

6. 6Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

7. 7Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

8. 8Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.

9. 9Cancer Genomics Research Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland.

10. 10Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

11. 11Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

12. 12University of Ghana, Accra, Ghana.

13. 13Loma Linda University, School of Public Health, Loma Linda, California.

14. 14Usher Institute and CRUK Edinburgh Centre, University of Edinburgh, Edinburgh, United Kingdom.

Abstract

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.

Funder

European Union’s Horizon 2020 Research and Innovation Programme

Wellcome Trust

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

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