Men who inherit mutations in a gene called TP53 have a high risk of developing aggressive prostate cancer, a multicenter research team in the United States has found.
The findings were reported in the journal European Urology. Researchers from more than a dozen institutions across the United States collaborated on the study. Dr. Kara N. Maxwell, assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania is the paper’s lead author.
The TP53 gene instructs cells to make tumor protein 53. This protein detects damaged DNA and determines if the DNA can be repaired. If it can, the protein initiates the DNA-repair process. If it cannot, the protein triggers a process that causes the cell to self-destruct, preventing it from replicating with damaged–and potentially cancer-causing–DNA.
“TP53 is a tumor suppressor gene that by detecting DNA damage serves as the ‘Guardian of the Genome. But mutations in TP53 commonly develop in cancers, and when its protection is lost the cancers can go wild,” said Dr. Colin Pritchard, professor of laboratory medicine and pathology at the University of Washington School of Medicine. He is also a researcher at the Brotman Baty Institute for Precision Medicine in Seattle. Pritchard was the corresponding author for the study.
Harmful mutations in TP53 also can be inherited and cause a rare condition called Li-Fraumeni syndrome, named after Drs. Frederick Li and Joseph Fraumeni from the U.S. National Cancer Institute who first described it in 1969.
People with LFS tend to develop multiple cancers starting in childhood. Although the syndrome is associated with many different types of cancer, including some in breast, bone and soft tissues, such as muscles, the effect of TP53 variants on the risk of prostate cancer was unknown.
To find out the role of TP53 variants, the researchers looked at the incidence of prostate cancer in a group of men with LFS and the prevalence of inherited TP53 mutations in men with prostate cancer.
In the group of 163 men with LFS, the researchers found that 31 had had prostate cancer and, of the remaining 117 men who did not have the cancer when they were initially tested, six more were diagnosed with the disease in the next seven years. The results indicate that men with LFS had a 25-fold increased risk of prostate cancer compared to the general male population.
