Biomedicine

Abstract

Introduction and aim Breast cancer is a leading cause of death in Mizoram, Northeast India. Germline mutations in breast cancer patients have been associated with factors such as age, pathology, and ethnicity. This study aimed to screen for germline mutations in select marker genes in a high-risk tribal population to assess their role in breast cancer. Materials and methods Fifty unrelated breast cancer patients and fifty healthy controls were screened for mutations using direct Sanger sequencing. This analysis covered the entire coding regions of the BRCA1 gene and the frequently mutated exons of TP53, PTEN, CDH1, CHEK2, and XRCC2 genes. Tools such as Mutation Taster, Align GVGD, PolyPhen-2, and various databases were utilised to determine the pathogenicity of the identified polymorphisms. Results Eight polymorphisms were identified in the BRCA1 gene, including a novel exon 15 variant (g.95900A>T: c.4772A>T: p.P1544P). All polymorphisms were of silent mutation with no significant amino acid changes. Additionally, no genetic alterations were detected in the studied exons of the TP53, PTEN, CDH1, CHEK2, and XRCC2 genes. Conclusion The absence of pathogenic germline mutations in this high-risk population highlights the unique genetic origins and the need to explore other germline gene variants or novel genes in breast cancer development. Breast cancer is a complex and heterogeneous disease with variable clinical course in patients, and hence understanding of key genes involved is crucial. This study indicates the need to evaluate tumor samples in under-represented populations to better understand gene mutations, which could enhance personalized genetic screening approaches.