Understanding the prevalence of germline oncogenic biomarker variants across the Indian population

Abstract

Background: Germline variants have traditionally been used for determining carrier status in heritable cancer families. However, studies are increasingly finding use of germline variants as therapeutic, diagnostic and prognostic biomarkers used to guide therapy decisions in cancer treatment. Objectives: To study the prevalence of mutation specific oncogenic biomarkers in the Indian population and analyze their presence across disease cohorts Materials and Methods: We annotate the IndiGen data obtained from whole genome sequencing of 1029 self-declared healthy Indian individuals with biomarker information obtained from the OncoKB knowledgebase, a repository of evidence-based information about somatic biomarkers and structural alterations in patient tumors. Results: In our study we have discovered 34 biomarker variants of therapeutic actionability across 16 genes linked with 23 unique drugs or drug combinations in 23 unique types of cancer disease in the Indian population. In all, we have found 52 biomarker variants with 172 different biomarker types including therapeutic, resistance, diagnostic, and prognostic. We establish that 4.3% of the Indian population are carriers of therapeutic, and 2.13% are carriers of both diagnostic as well as prognostic germline biomarkers. Finally, we also establish the prevalence of 42 biomarker variants across the 23 genes in both AD and AR modes of inheritance in the Indian population.