Germline sequence variants contributing to cancer susceptibility in South African breast cancer patients of African ancestry

Dewald Eygelaar,Fourie Joubert,Elizabeth J Van Rensburg

doi:10.1038/s41598-022-04791-1

Dewald Eygelaar, Fourie Joubert + Show 1 more

Open Access

https://doi.org/10.1038/s41598-022-04791-1

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Journal: Scientific Reports	Publication Date: Jan 17, 2022
Citations: 4	License type: open-access

Affiliation: University of Pretoria

Abstract

Since the discovery of the breast cancer susceptibility genes, BRCA1 and BRCA2, various other genes conferring an increased risk for breast cancer have been identified. Studies to evaluate sequence variants in cancer predisposition genes among women of African ancestry are limited and mostly focused on BRCA1 and BRCA2. To characterize germline sequence variants in cancer susceptibility genes, we analysed a cohort of 165 South African women of self-identified African ancestry diagnosed with breast cancer, who were unselected for family history of cancer. With the exception of four cases, all others were previously investigated for BRCA1 and BRCA2 deleterious variants, and were negative for pathogenic variants. We utilized the Illumina TruSight cancer panel for targeted sequencing of 94 cancer susceptibility genes. A total of 3.6% of patients carried a pathogenic/likely pathogenic variant in a known breast cancer susceptibility gene: 1.2% in BRCA1, 0.6% in each of BRCA2, ATM, CHEK2 and PALB, none of whom had any family history of breast cancer. The mean age of patients who carried deleterious variant in BRCA1/BRCA2 was 39 years and 8 months compared to 47 years and 3 months among women who carried a deleterious variant in other breast cancer susceptibility genes.

Highlights

Since the discovery of the breast cancer susceptibility genes, BRCA1 and BRCA2, various other genes conferring an increased risk for breast cancer have been identified
With the exception of four cases, all others were previously investigated for BRCA1 and BRCA2 pathogenic variants, and were negative for pathogenic/likely pathogenic BRCA1/BRCA2 variants We used targeted next-generation sequencing of a multigene panel, comprised of 94 cancer susceptibility genes (Illumina TruSight cancer panel) in order to assess the frequency of deleterious germline variants in this cohort
This study screened 165 South African breast cancer patients of African ancestry for the presence of deleterious germ line sequence variants in 94 genes associated with hereditary cancer

Summary

Introduction

Since the discovery of the breast cancer susceptibility genes, BRCA1 and BRCA2, various other genes conferring an increased risk for breast cancer have been identified. To characterize germline sequence variants in cancer susceptibility genes, we analysed a cohort of 165 South African women of self-identified African ancestry diagnosed with breast cancer, who were unselected for family history of cancer. There is a paucity of data on sequence variants in cancer predisposition genes among women of African descent/ancestry with breast cancer, who are unselected for age at diagnosis, or family history of cancer. To date only two studies in Africa, one on Nigerian women[13], and one on women from Uganda and Cameroon[14], have used multigene panel sequencing to test for germline variants in patients, unselected for family history or age at diagnosis. We included South African women of African ancestry (self-identified) diagnosed with breast cancer, who were unselected for age at diagnosis or family history of cancer. With the exception of four cases, all others were previously investigated for BRCA1 and BRCA2 pathogenic variants, and were negative for pathogenic/likely pathogenic BRCA1/BRCA2 variants We used targeted next-generation sequencing of a multigene panel, comprised of 94 cancer susceptibility genes (Illumina TruSight cancer panel) in order to assess the frequency of deleterious germline variants in this cohort

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Conclusion