Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

Abstract Background: Breast cancer is the most prevalent cancer and leading cause of death among women globally. The present study focuses on screening germline mutations of breast cancer susceptibility genes among the unexplored Mizo breast cancers of culturally and historically homogenous population, living a unique life style habits in terms of diet and tobacco usage. Methods Mutation screening was performed using Sanger sequencing in complete coding region of BRCA1 and frequently mutated exons of TP53, PTEN, CDH1, CHEK2 and XRCC2. Several online mutation prediction tools and databases were used to check the pathogenicity of the polymorphisms observed. Results: We observed eight polymorphisms in total, in which, one variants p.P1544P in BRCA1 gene was found to be novel. No variants were found to have a potential impact on protein since all the polymorphisms are of silent substitutions. No genetic alteration was observed in the studied exons of each of TP53, PTEN, CDH1, CHEK2 and XRCC2. Conclusion: To our knowledge, the present study focusing on familial breast cancer is the first time to analyzed the prevalence of breast cancer susceptibility gene mutations using direct sequencing in Mizo population. Even though, we do not find significant amino acid change, our results suggest the need for further evaluation of broader panel genes and a challenge to screen larger sample size to establish the contribution of these gene mutations in this population.