WSLHD
Skip navigation
Please use this identifier to cite or link to this item: https://wslhd.intersearch.com.au/wslhdjspui/handle/1/9580
TitleCancer Risks Associated With TP53 Pathogenic Variants: Maximum Likelihood Analysis of Extended Pedigrees for Diagnosis of First Cancers Beyond the Li-Fraumeni Syndrome Spectrum
Authors: Fortuno, C.;Feng, B. J.;Carroll, C.;Innella, G.;Kohlmann, W.;Lazaro, C.;Brunet, J.;Feliubadalo, L.;Iglesias, S.;Menendez, M.;Teule, A.;Ballinger, M. L.;Thomas, D. M.;Campbell, A.;Field, M.;Harris, M.;Kirk, Judy;Pachter, N.;Poplawski, N.;Susman, R.;Tucker, K.;Wallis, M.;Williams, R.;Cops, E.;Goldgar, D.;James, P. A.;Spurdle, A. B.
WSLHD Author: Kirk, Judy
Subjects: United States;Li-Fraumeni Syndrome;Genes, p53;Pedigree;Tumor Suppressor Protein p53;Genetic Predisposition to Disease;Breast Neoplasms
Issue Date: 2024
Citation: JCO Precision Oncology 8:e2300453, 2024
Abstract: PURPOSE: Establishing accurate age-related penetrance figures for the broad range of cancer types that occur in individuals harboring a pathogenic germline variant in the TP53 gene is essential to determine the most effective clinical management strategies. These figures also permit optimal use of cosegregation data for classification of TP53 variants of unknown significance. Penetrance estimation can easily be affected by bias from ascertainment criteria, an issue not commonly addressed by previous studies. MATERIALS AND METHODS: We performed a maximum likelihood penetrance estimation using full pedigree data from a multicenter study of 146 TP53-positive families, incorporating adjustment for the effect of ascertainment and population-specific background cancer risks. The analysis included pedigrees from Australia, Spain, and United States, with phenotypic information for 4,028 individuals. RESULTS: Core Li-Fraumeni syndrome (LFS) cancers (breast cancer, adrenocortical carcinoma, brain cancer, osteosarcoma, and soft tissue sarcoma) had the highest hazard ratios of all cancers analyzed in this study. The analysis also detected a significantly increased lifetime risk for a range of cancers not previously formally associated with TP53 pathogenic variant status, including colorectal, gastric, lung, pancreatic, and ovarian cancers. The cumulative risk of any cancer type by age 50 years was 92.4% (95% CI, 82.2 to 98.3) for females and 59.7% (95% CI, 39.9 to 81.3) for males. Females had a 63.3% (95% CI, 35.6 to 90.1) cumulative risk of developing breast cancer by age 50 years. CONCLUSION: The results from maximum likelihood analysis confirm the known high lifetime risk for the core LFS-associated cancer types providing new risk estimates and indicate significantly increased lifetime risks for several additional cancer types. Accurate cancer risk estimates will help refine clinical recommendations for TP53 pathogenic variant carriers and improve TP53 variant classification.
URI: https://wslhd.intersearch.com.au/wslhdjspui/handle/1/9580
DOI: https://dx.doi.org/10.1200/PO.23.00453
Journal: JCO Precision Oncology
Type: Journal Article
Facility: Westmead
Appears in Collections:Westmead Hospital 2019 - 2024

Files in This Item:
There are no files associated with this item.


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