Objective: The objective of this study was to determine the prevalence and spectrum of genetic mutations linked to inherited breast and ovary cancer (HBOC) in the Indian population, and to evaluate the correlation of BRCA mutation types, frequency, and incidence with age, gender, and personal and family history.
Methods: A retrospective cohort of 500 Indian HBOC patients, meeting NCCN criteria who underwent BRCA1/2 testing from 2017 to 2023 were shortlisted for this study. The anonymized data was retrieved from medical records. Genetic analysis was conducted using Next Generation Sequencing (NGS) on the Thermo Ion GeneStudio™ S5 System, with positive mutations confirmed via Sanger sequencing. Peripheral blood samples were processed for DNA extraction, library preparation, and variant classification following ACMG guidelines.
Results: Out of the 500 patients, 119 (23.8%) were positive for BRCA mutations, and 381 (76.2%) were negative. The prevalence of BRCA pathogenesis, likely pathogenicity, and variants of uncertain significance (VUSs) were 14.8%, 1.6%, and 7.4%, respectively. A total of 128 mutations were detected in the positive BRCA1/2 patients. A statistically significant correlation was found between BRCA mutations with the patient and family history. A total of 38.8% of the patients with mutations had a family history of BC, OC or BC/OC, while 7.6% had other cancers. BRCA mutations were predominant (26.2%) in the age group of 46-65 Y. Among the 128 mutations, 59.3% (76/128) and 40.6% (52/12) of the patients had mutations in BRCA1 and BRCA2, respectively. Missense mutations were the most common in both the BRCA1 (30.26%) and BRCA2 (55.77%) genes, followed by frameshift (22.3%) and nonsense (17.3%) mutations in BRCA1 and BRCA2, respectively.
Conclusion: BRCA positivity was detected in 23.8% of the patients. A statistically significant association was shown between BRCA mutations and patient and family history.
Keywords: Developing countries; Ovarian Cancer; breast cancer; next generation sequencing.