Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Penetrance Estimates Over Time to First and Second Primary Cancer Diagnosis in Families with Li-Fraumeni Syndrome: A Single Institution Perspective

Authors
Shin, Seung JunDodd-Eaton, Elissa B.Gao, FanBojadzieva, JasminaChen, JingxiaoKong, XianhuaAmos, Christopher, INing, JingStrong, Louise C.Wang, Wenyi
Issue Date
15-1월-2020
Publisher
AMER ASSOC CANCER RESEARCH
Citation
CANCER RESEARCH, v.80, no.2, pp.347 - 353
Indexed
SCIE
SCOPUS
Journal Title
CANCER RESEARCH
Volume
80
Number
2
Start Page
347
End Page
353
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/57990
DOI
10.1158/0008-5472.CAN-19-0725
ISSN
0008-5472
Abstract
Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder associated with TP53 germline mutations and an increased lifetime risk of multiple primary cancers (MPC). Penetrance estimation of time to first and second primary cancer within LFS remains challenging because of limited data and the difficulty of characterizing the effects of a primary cancer on the penetrance of a second primary cancer. Using a recurrent events survival modeling approach that incorporates a family-wise likelihood to efficiently integrate the pedigree structure, we estimated the penetrance for both first and second primary cancer diagnosis from a pediatric sarcoma cohort at MD Anderson Cancer Center [MDACC, Houston, TX; number of families = 189; single primary cancer (SPC) = 771; and MPC = 87]. Validation of the risk prediction performance was performed using an independent MDACC clinical cohort of TP53 tested individuals (SPC = 102 and MPC = 58). These findings showed that an individual diagnosed at a later age was more likely to be diagnosed with a second primary cancer. In addition, TP53 mutation carriers had a HR of 1.65 (95% confidence interval, 1.1-2.5) for developing a second primary cancer versus SPC. The area under the ROC (AUC) curve for predicting individual outcomes of MPC versus SPC was 0.77. In summary, we provide the first set of penetrance estimates for first and second primary cancer for TP53 germline mutation carriers and demonstrate its accuracy for cancer risk assessment. Significance: These findings present an open-source R package LFSPRO that could be used for genetic counseling and health management of individuals with LFS as it estimates the risk of both first and second primary cancer diagnosis.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Political Science & Economics > Department of Statistics > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Altmetrics

Total Views & Downloads

BROWSE