Women with breast carcinoma diagnosed before 40 years of age with a strong familial risk have a greater prevalence of germline BRCA1 or BRCA2 variants than late onset breast cancer. Previously germline variants in BRCA1 and BRCA2 genes were characterized in a cohort of Sri Lankan breast cancer patients unselected for age of onset. This study focused on young breast cancer patients who were screened for previously identified hotspot regions in BRCA2 gene. A total of 48 young breast cancer patients with family history of cancer and 25 healthy controls were studied. Direct sequencing was used to detect pathogenic and other sequence variants in the hotspot regions of BRCA2 gene. Thirty-six sequence variants including seven pathogenic (c.2411_2412delAA/p.Glu804Valfs*2, c.2500_2501insG/p.Leu834Cysfs*4, c.3881T>G/p.Leu1294*, c.4768A>T/p.Lys1590*, c.5645C>G/p.Ser1882*, c.5747delC/p.His1916Phefs*3, c.6728C>T/p.Ser2243Phe) and two likely pathogenic (c.1922C>T and c.3378A>T) variants, two intronic variants of unknown significance (c.1910-74T>C, c.1910-51G>T), two variants of uncertain significance (c.2324C>T c.5104C>T) and 23 benign variants were detected. Among them, seven were novel (pathogenic 5 and likely pathogenic 2). Prevalence of pathogenic and likely pathogenic variants in the hotspots regions of BRCA2 was 23 and 6.3 % respectively in this cohort. This justifies BRCA2 variant testing in young breast cancer patients with family history of cancer in Sri Lanka.
Keywords: BRCA2; Hotspot regions; Sri Lanka; Young breast cancer patients.