Prevalence and Spectrum of Breast Cancer Inherited Mutations in Uganda and Cameroon Women

Abstract

Background: Breast cancer among indigenous Africans is characterized by higher prevalence of triple-negative disease and poor prognosis. A previous study in Nigeria reported a strikingly high prevalence of deleterious germline mutations in BRCA1 and BRCA2 among Nigerian women with breast cancer. It is unknown if this is true in other sub-Saharan African countries. Aim: The objective of this study is to determine the frequency of germline mutations among an unselected sample of women in Africa. Methods: We conducted a case-control study of breast cancer in Uganda and Cameroon to investigate genetic and nongenetic risk factors for breast cancer. Breast cancer cases were enrolled in two tertiary hospitals in the two countries, unselected for age at diagnosis and family history. Controls who were free of breast cancer were enrolled in the same hospitals and matched to cases on age. A 24-gene sequencing panel was used to test germline mutations in cases and controls. Results: There were 176 cases and 177 controls with a mean age at diagnosis of 46.2 years for cases and mean age at interview of 46.7 years for controls. Among cases, 18.2% carried a pathogenic mutation in a breast cancer gene: 6.3% in BRCA1, 6.3% in BRCA2, 1.7% in ATM, 1.1% in PALB2, 0.6% in BARD1, 0.6% in CDH1, 0.6% in TP53, and 1.2% in any of 17 other genes. Among controls, 2.3% carried a pathogenic mutation in one of the 24 susceptibility genes. Cases were 9.6-fold more likely to carry a mutation compared with controls (odds ratio=9.61, 95% confidence interval: 3.28-38.1; P < 0.001). The mean age of breast cancer cases with pathogenic BRCA1 mutations was 38.3 years compared with 46.7 years among other cases without such mutations ( P = 0.03). There was a trend that cases with a positive family history had higher chance of carrying a mutation (33.3%) than cases without (17.1%), but few cases reported a positive family history. Conclusion: Our findings confirm the earlier report of a high proportion of deleterious mutations in BRCA1 and BRCA2 among breast cancer patients in sub-Saharan Africa. As most of these women present with advanced breast cancer, there is an urgent need to improve access to genomic testing and life saving cancer medicines including chemotherapy and clinical trials of novel agents like PARP inhibitors. Given the high burden of inherited breast cancer, genetic risk assessment should be integrated into cancer control plans in sub-Saharan Africa.