Germline pathogenic variants in <i>BRCA1-,</i> <i>BRCA2-</i> , and <i>PALB2-</i> genes among Ethiopian young women and men diagnosed with breast cancer.

Abstract

10567 Background: Breast cancer incidence is rapidly increasing in low-and-middle-income countries (LMICs), where access to care is limited and survival outcome is poor. Young women and men are overrepresented among breast cancer (BC) patients diagnosed in LMICs in Sub-Saharan Africa (SSA), for reasons not yet fully understood. As hereditary cancer is more common in young women and men with BC, genetic factors may play a significant role. Even though carriers of germline pathogenic variants (PV) in the genes BRCA1 , BRCA2 , and PALB2 have a very high risk of BC, studies of PV in these genes are very limited in SSA. In order to increase knowledge, this study investigated the prevalence of PV in high-risk BC susceptibility genes in young women and men diagnosed with BC in Ethiopia. Methods: This is a descriptive cross-sectional study. One-hundred young women (age 18-39) and men (all ages) diagnosed with invasive BC were included from Departments of Oncology and Surgery at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. Potential participants were given oral and written information by a trained physician, and those consenting were included in the study. Basic patient- and tumor characteristic as well as information about family history was collected. DNA was extracted from blood samples, before shipment to BRCAlab, Lund University, Sweden for genetic analysis of genes BRCA1 , BRCA2 and PALB2 , using a gene panel and next generation sequencing on an Illumina platform. Results: Genetic analysis results were available for 89 study patients. There was a high proportion (21.3%) of PV in tested genes. In total, 19 PV were found in BRCA1 (n = 7), BRCA2 (n = 8) and PALB2 (n = 4). One of the PV was in a male. There were five individuals with an identical PV in BRCA1 (c.4524G &gt; A, NM_007294.3), three individuals with identical PV in BRCA2 (c.5159C &gt; A, NM_000059.3), and two individuals with identical PV in PALB2 (c.1216delG, NM_024675.4). Two novel PV not previously reported in literature were found, BRCA1 c.5278-864_5332+621del, NM_007294.3 and PALB2 c.1169_1170del, NM_024675.4. Conclusions: This study demonstrates that germline PV in BRCA1 , BRCA2 and PALB2 are common among young women and men diagnosed with BC in Ethiopia, with over 1 out of 5 patients carrying a PV. Genetic predisposition appears to play an important role in the tumor genesis in the studied group. Multiple patients carried identical PV, which could indicate that the detected PV are founder variants. Since the majority of the patients in Ethiopia are young, and male BC seem more prevalent compared to in western countries, efforts directed to these groups and development of services for genetic testing and follow-up programs for carriers of PV should be further emphasized. This approach has the potential to reduce BC incidence, morbidity and mortality through increased awareness, risk-reducing procedures and earlier cancer detection.