The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein regulates cell division by keeping cells from growing and dividing too fast or in an uncontrolled way. A recent study demonstrated men who have mutations in a gene called TP53 have a high risk of developing aggressive prostate cancer.
The findings were reported in the journal European Urology in a paper titled, “Inherited TP53 Variants and Risk of Prostate Cancer,” and was led by Kara N. Maxwell, MD, PhD, an oncologist and assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania.
“Inherited germline TP53 pathogenic and likely pathogenic variants (gTP53) cause autosomal dominant multicancer predisposition including Li-Fraumeni syndrome (LFS),” the researchers wrote. “However, there is no known association of prostate cancer with gTP53.”
The researchers sought to determine whether gTP53 predisposes to prostate cancer.
“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 Colin Pritchard, MD, PhD, corresponding author of the study and professor of laboratory medicine and pathology at the University of Washington School of Medicine.
The researchers looked at the incidence of prostate cancer in a group of men with LFS, a rare condition that can be caused by mutations in TP53.
In the group of 163 men with LFS, the researchers observed that 31 had prostate cancer and, of the remaining 117 men who did not have 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.
Among the nearly 7,000 men they studied who had had prostate cancer, 38 had inherited a deleterious TP53 variant.
“That rate is way higher than is seen in the average prostate cancer population,” Pritchard said. “In fact, it’s fairly rare to be diagnosed with prostate cancer at such a late stage.”
The connection between TP53 variants and prostate cancer in LFS patients may have gone undetected because, for many years, these patients typically did not live long enough to develop the disease, according to Pritchard.
“Prostate cancer is a disease of older men,” he said. “But now, with screening, many men with Li-Fraumeni syndrome are living into their 40s, 50s, 60s, and 70s, when the risk of prostate cancer is higher.”
The findings suggest men with LFS should be routinely screened for prostate cancer and men undergoing cancer-risk genetic testing should be checked for mutations in this gene as well.