  Identifying individuals who are at high risk of cancer due to inherited
germline mutations is critical for effective implementation of personalized
prevention strategies. Most existing models to identify these individuals focus
on specific syndromes by including family and personal history for a small
number of cancers. Recent evidence from multi-gene panel testing has shown that
many syndromes once thought to be distinct are overlapping, motivating the
development of models that incorporate family history information on several
cancers and predict mutations for more comprehensive panels of genes.
  Once such class of models are Mendelian risk prediction models, which use
family history information and Mendelian laws of inheritance to estimate the
probability of carrying genetic mutations, as well as future risk of developing
associated cancers. To flexibly model the complexity of many cancer-mutation
associations, we present a new software tool called PanelPRO, a R package that
extends the previously developed BayesMendel R package to user-selected lists
of susceptibility genes and associated cancers. The model identifies
individuals at an increased risk of carrying cancer susceptibility gene
mutations and predicts future risk of developing hereditary cancers associated
with those genes. Additional functionalities adjust for prophylactic
interventions, known genetic testing results, and risk modifiers such as race
and ancestry. The package comes with a customizable database with default
parameter values estimated from published studies.
  The PanelPRO package is open-source and provides a fast and flexible back-end
for multi-gene, multi-cancer risk modeling with pedigree data. The software
enables the identification of high-risk individuals, which will have an impact
on personalized prevention strategies for cancer and individualized decision
making about genetic testing.
