@misc{shin_dodd_peng_bojadzieva_chen_amos_mai_savage_ballinger_thomas_et al._2019, 
  title={Risk of differential cancer types over age in families with Li-Fraumeni syndrome: a validation study using multi-center cohorts}, 
  DOI={10.1101/567727}, 
  abstractNote={<jats:p>Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses. An accurate estimation of the penetrance of different cancer types in LFS is crucial to improve the clinical characterization and management of high-risk individuals of LFS. Our competing risk-based statistical model incorporates the pedigree structure efficiently into the penetrance estimation and corrects for the ascertainment bias. A set of TP53 penetrance for three cancer types (breast, BR/sarcoma, SA/others, OT) involved in LFS is then estimated from 186 pediatric-sarcoma families collected at MD Anderson Cancer Center. The penetrance was then validated on a mixed cohort of clinically ascertained families with cancer (total number of families=668). The age-dependent onset probability distributions of specific cancer types are different. For breast cancer, the TP53 penetrance goes up at an earlier age than the reported BRCA1/2 penetrance. We validated the prediction performance of the penetrance estimates via two independent cohorts combined (BR=85, SA=540, OT=158). We obtained areas under the ROC curves (AUCs) of 0.92 (BR), 0.75 (SA), and 0.81 (OT). Our R package, LFSPRO, provides risk estimates for the diagnosis of breast cancer, sarcoma, other cancers or death before cancer diagnosis in future.</jats:p>}, 
  publisher={Cold Spring Harbor Laboratory}, 
  author={Shin and Dodd and Peng and Bojadzieva and Chen and Amos and Mai and Savage and Ballinger and Thomas and et al.}, 
  year={2019}, 
  month={Mar}
  }