Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon

Abstract

Background: Sub-Saharan Africa (SSA) has a high proportion of premenopausal hormone receptor negative breast cancer. Previous studies reported a strikingly high prevalence of germline mutations in BRCA1 and BRCA2 among Nigerian patients with breast cancer. It is unknown if this exists in other SSA countries.Methods: Breast cancer cases, unselected for age at diagnosis and family history, were recruited from tertiary hospitals in Kampala, Uganda and Yaound e, Cameroon. Controls were women without breast cancer recruited from the same hospitals and age-matched to cases. A multigene sequencing panel was used to test for germline mutations.Results: There were 196 cases and 185 controls with a mean age of 46.2 and 46.6 years for cases and controls, respectively. Among cases, 15.8% carried a pathogenic or likely pathogenic mutation in a breast cancer susceptibility gene: 5.6% in BRCA1, 5.6% in BRCA2, 1.5% in ATM, 1% in PALB2, 0.5% in BARD1, 0.5% in CDH1, and 0.5% in TP53. Among controls, 1.6% carried a mutation in one of these genes. Cases were 11-fold more likely to carry a mutation compared with controls (OR ¼ 11.34; 95% confidence interval, 3.44-59.06; P < 0.001). The mean age of cases with BRCA1 mutations was 38.3 years compared with 46.7 years among other cases without such mutations (P ¼ 0.03).Conclusions: Our findings replicate the earlier report of a high proportion of mutations in BRCA1/2 among patients with symptomatic breast cancer in SSA.Impact: Given the high burden of inherited breast cancer in SSA countries, genetic risk assessment could be integrated into national cancer control plans.

BARD1 Pathogenic Variants Are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort

“…It is worth emphasizing that we have performed a screening of CNVs in our cohort of HC patients, resulting in the identification of two large deletions (exons 7 to 8 and exons 7 to 11), accounting for 10.5% of the PVs. To our knowledge, only a small fraction of published studies have also performed this analysis and only seven CNVs have been identified so far: exon 1 deletion [33], exon 2 deletion [34], exon 1 to 6 deletion [35], exon 5 to 7 deletion [36], exon 8 to 11 deletion [37] and two whole-gene deletions [37,38]. While no CNVs were identified in the gnomAD SV control population dataset, analysis of BARD1 CNVs in HC cohorts is strongly recommended considering the significant contribution in our series of this kind of variant.…”

Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean

“…There, the rates of inherited breast cancer range between 14.1% in Nigeria and 15.2% in Uganda and Cameroon. Rates of inherited breast cancer in African American women range between 12.4% in those 50 years and younger and 22% in those reporting a family history of cancer 9,10,24,25. This study's findings suggest that, irrespective of island of birth, native residents of Caribbean islands have high rates of inherited breast and ovarian cancer.In Barbados, 18% of patients with breast and ovarian cancer had a germline variant with only 1 recurrent, pathogenic variant in BRCA1, which was found in 4 unrelated individuals.…”

Summary of BARD1 Mutations and Precise Estimation of Breast and Ovarian Cancer Risks Associated with the Mutations

“…A total of 265 studies were further assessed by the full-text review, of which 145 studies not meeting the criteria (described in the Methods section and Figure S1 ) were excluded. Finally, for the analysis, we included 123 studies: 120 studies from the PubMed search and 3 hand-searched studies [ 15 , 16 , 18 , 19 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , …”

“…Only five CNVs were identified in the BARD1 gene in the selected studies. Deletion of exon 1, deletion of exon 2, and deletion of the entire gene (exons 1-11) were identified in BC patients [26,81,125], while deletion of exons 8-11 and deletion of the entire gene were identified in OC patients [34]. Of note, no large deletions were reported in the BARD1 gene in gnomAD population controls (~10,800 cases tested), and only 1 deletion (exon 4-11) was identified among noncancer FLOSSIES controls (9884 cases tested).…”