Mutation Analysis of the BRCA1 and BRCA2 Genes in Early-Onset, Familial, and Sporadic Breast Cancer Among the South Indian Population

Breast cancer is the most common cancer in women worldwide. While BRCA1 and BRCA2 mutations have been extensively studied in the Indian population through heterogeneous studies, their role in breast cancer among the south Indian population remains less explored. This study aimed to assess BRCA1/2 mutations in early-onset, family history, and sporadic breast cancer, as well as in healthy females of South Indian population. We evaluated BRCA1/2 gene mutations in 200 breast cancer cases and 200 healthy controls using SSCP and sequencing. BRCA1 variants were identified in 14% and BRCA2 variants in 9.5% of cases. A spectrum of 13 different pathogenic variants was found—8 in BRCA1 and 5 in BRCA2. The most common BRCA1 variant was c.68_69delAG (p. Glu23Valfs*17), present in 4.5% (9/200) of cases, followed by c.3596delGAAA, c.4184delTCAA, c.1608delT, and c.1027delA. In BRCA2, the most common variant was c.3861_3864delTAAT, identified in 6 cases, followed by c.286G > C, c.203G > C, and c.3749_50delAA. We observed BRCA1 and BRCA2 gene mutations in a relatively higher proportion of 31% (26/84) among early-onset breast cancer, 25.7% (33/128) among women with hereditary breast cancer, and 27.7% (20/72) among women with sporadic breast cancer. We recommend genetic screening for BRCA1 and BRCA2 among women with a family history of breast cancer at regular intervals to enable early detection and prevention of the disease’s severe forms.