Bayesian estimation of a semiparametric recurrent event model with applications to the penetrance estimation of multiple primary cancers in Li-Fraumeni syndrome

Seung Jun Shin, Jialu Li, Jing Ning, Jasmina Bojadzieva, Louise C. Strong, Wenyi Wang

    Research output: Contribution to journalArticlepeer-review

    3 Citations (Scopus)

    Abstract

    A common phenomenon in cancer syndromes is for an individual to have multiple primary cancers (MPC) at different sites during his/her lifetime. Patients with Li-Fraumeni syndrome (LFS), a rare pediatric cancer syndrome mainly caused by germlineTP53 mutations, are knownto have a higher probability of developing a second primary cancer than those with other cancer syndromes. In this context, it is desirable to model the development of MPC to enable better clinical management of LFS. Here, we propose a Bayesian recurrent event model based on a non-homogeneous Poisson process in order to obtain penetrance estimates forMPC related to LFS. We employed a familywise likelihood that facilitates using genetic information inherited through the family pedigree and properly adjusted for the ascertainment bias that was inevitable in studies of rare diseases by using an inverse probability weighting scheme. We applied the proposed method to data on LFS, using a family cohort collected through pediatric sarcoma patients at MDAnderson Cancer Center from 1944 to 1982. Both internal and external validation studies showed that the proposed model provides reliable penetrance estimates for MPC in LFS, which, to the best of our knowledge, have not been reported in the LFS literature.

    Original languageEnglish
    Pages (from-to)467-482
    Number of pages16
    JournalBiostatistics
    Volume21
    Issue number3
    DOIs
    Publication statusPublished - 2020

    Bibliographical note

    © The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

    Keywords

    • Age-at-onset penetrance
    • Familywise likelihood
    • Li-Fraumeni syndrome
    • Multiple primary cancers
    • Recurrent event model.

    ASJC Scopus subject areas

    • Statistics and Probability
    • Statistics, Probability and Uncertainty

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