Web-Based User Interface for Fam3PRO: A Multigene, Multicancer Risk Prediction Model for Families With Cancer History

PURPOSE Hereditary cancer risk is key to guiding screening and prevention strategies. Cancer risks can vary by individual because of the presence or absence of high- and moderate-risk pathogenic variants (PVs) in cancer-associated genes, in addition to sex, age, and other risk factors. We previously developed Fam3PRO, a flexible multigene, multicancer Mendelian risk prediction model that estimates a patient's risk of carrying a PV in hereditary cancer genes and their future risk of developing several types of cancers. The Fam3PRO R package includes 22 genes with 18 associated cancers, allowing users to build customized submodels from any gene-cancer set. However, the current R package lacks a user interface (UI), limiting its practical use in clinical settings. Therefore, we aim to develop a web-based UI for broader use of the Fam3PRO functionalities. METHODS The Fam3PRO UI (F3PI), built using R Shiny, collects and formats inputs including family health history, genetic test results, and other risk factors. Pedigree data are interactively visualized and modified using pedigreejs, whereas the backend Fam3PRO model takes all the inputs to generate carrier probabilities and future cancer risks, presented through an interactive UI. RESULTS F3PI streamlines the collection of patient and family history data, which is analyzed by the Fam3PRO models to provide personalized cancer risks for each proband across 18 cancers, as well as probabilities that a proband has a PV in up to 22 hereditary cancer genes. These results are returned to the user, within 1 minute on average, and are available in both interactive and downloadable formats. CONCLUSION We have developed F3PI, an easy-to-use, interactive web application that makes cancer and genetic risk information more accessible to providers and their patients.