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Identifying individuals who are at high risk of cancer due to inheritedgermline mutations is critical for effective implementation of personalizedprevention strategies. Most existing models to identify these individuals focuson specific syndromes by including family and personal history for a smallnumber of cancers. Recent evidence from multi-gene panel testing has shown thatmany syndromes once thought to be distinct are overlapping, motivating thedevelopment of models that incorporate family history information on severalcancers and predict mutations for more comprehensive panels of genes.  Once such class of models are Mendelian risk prediction models, which usefamily history information and Mendelian laws of inheritance to estimate theprobability of carrying genetic mutations, as well as future risk of developingassociated cancers. To flexibly model the complexity of many cancer-mutationassociations, we present a new software tool called PanelPRO, a R package thatextends the previously developed BayesMendel R package to user-selected listsof susceptibility genes and associated cancers. The model identifiesindividuals at an increased risk of carrying cancer susceptibility genemutations and predicts future risk of developing hereditary cancers associatedwith those genes. Additional functionalities adjust for prophylacticinterventions, known genetic testing results, and risk modifiers such as raceand ancestry. The package comes with a customizable database with defaultparameter values estimated from published studies.  The PanelPRO package is open-source and provides a fast and flexible back-endfor multi-gene, multi-cancer risk modeling with pedigree data. The softwareenables the identification of high-risk individuals, which will have an impacton personalized prevention strategies for cancer and individualized decisionmaking about genetic testing.

PanelPRO: A R package for multi-syndrome, multi-gene risk modeling for individuals with a family history of cancer