Mutation prevalence tables for hereditary cancer derived from multi-gene panel testing

Abstract

PurposeMulti-gene panel testing for cancer predisposition mutations is becoming routine in clinical care. However, the gene content of panels offered by testing laboratories vary significantly, and data on mutation detection rates by gene and by panel is limited, causing confusion among clinicians on which test would be the most appropriate to order. Moreover, screening guidelines are not described in sufficient granularity to explain how differences in family, personal history, age, and other factors would affect the prevalence of finding a mutation in similar populations. The tool herein quantifies prevalence of mutations in hereditary cancer genes based on personalized clinical and demographic characteristics. MethodsUsing results from approximately 150,000 multi-gene panel tests conducted at Ambry Genetics, we built an interactive prevalence tool to explore how differences in ethnicity, age of onset, and personal and family history of different cancers affect the prevalence of pathogenic mutations in 31 cancer predisposition genes, across various clinically available hereditary cancer gene panels. ResultsOver 13,000 mutation carriers were identified in this high-risk population. Most of the cases were Non-Hispanic White (74%, n=109,537), but also provide an appreciable dataset for those identifying as Black (n=10,875), Ashkenazi Jewish (n=10,464), Hispanic (n=10,028), and Asian (n=7,090). The most prevalent cancer types were breast (50%), ovarian (6.6%), and colorectal (4.7%), which is expected based on genetic testing guidelines and clinician referral for testing. ConclusionThe Hereditary Cancer Multi-Gene Panel Prevalence Tool presented here can be used to provide insight into the prevalence of mutations on a per-gene and per-multigene panel basis, while conditioning on multiple custom phenotypic variables to include race and cancer type. The tool can be found at https://www.ambrygen.com/prevalence-tool.