Colin C. Pritchard, MD, Professor, Co-Director, Genetics, and Solid Tumors Laboratory, Precision Diagnostics Platform Head, Brotman Baty Institute For Precision Medicine, UW Medicine Laboratory Medicine & Pathology. In this video speaks about Inherited TP53 Variants and Risk of Prostate Cancer.
Link to Article:
https://newsroom.uw.edu/news/inherited-mutation-linked-aggressive-prostate-cancer
Link to Study:
https://www.sciencedirect.com/science/article/pii/S0302283821021394?via%3Dihub
Abstract:
Backstory:
Autosomal dominant multicancer predisposition, including Li-Fraumeni syndrome, is caused by inherited germline TP53 pathogenic and possibly pathogenic mutations (gTP53) (LFS). However, there is no documented link between gTP53 and prostate cancer.
Goal:
To see if gTP53 plays a role in prostate cancer predisposition.
Participants, setting, and design:
The incidence of prostate cancer in a cohort of LFS males and the prevalence of gTP53 in a prostate cancer cohort are investigated in this multi-institutional retrospective investigation.
Measurement of outcomes and statistical analysis:
The range of gTP53 mutations and clinical characteristics linked to prostate cancer were investigated.
Conclusions and limitations:
We found 31 occurrences of prostate cancer in 163 adult LFS males, including 26 of 54 under the age of 50. Over a median (interquartile range [IQR]) of 3.0 (1.3–7.2) years of follow-up, six LFS males without prostate cancer were diagnosed with prostate cancer, a 25-fold higher risk (95 percent confidence interval [CI] 9.2–55; p 0.0001). In the prostate cancer cohort, we found gTP53 in 38 of 6850 males (0.6%), a relative risk 9.1-fold greater than in population controls (95 percent CI 6.2–14; p 0.0001; gnomAD). We found hotspots in the locations of attenuated variations that aren’t linked to typical LFS. Somatic inactivation of the second TP53 allele was seen in two-thirds of the gTP53 prostate cancers studied. The median age at diagnosis for gTP53 prostate cancer cases in this study was 56 (IQR: 51–62), 44 percent had Gleason 8 tumors, and 29 percent had advanced disease at diagnosis.
Outcomes:
Prostate cancer incidence in LFS males and gTP53 prevalence in prostate cancer cohorts both point to gTP53 as a risk factor for aggressive prostate cancer. Prostate cancer should be included in LFS screening programs, and TP53 should be tested for prostate cancer susceptibility.
Summary of the patient:
Men with inherited pathogenic mutations in the TP53 gene are more likely to develop aggressive prostate cancer.