Research led by Vanderbilt University shows that disease-causing variants of the WNT9B gene increase prostate cancer risk if inherited.
As reported in JCO Precision Oncology, the researchers tested whether the link between WNT9B and prostate cancer risk was widespread by testing samples from four large biobanks in Europe and found that inheritance of the gene variant increased prostate cancer risk in male carriers from two to twelvefold.
Prostate cancer is the second most common cancer diagnosed in men and the second most common cause of cancer-related death in men. About 1.2 million new cases are diagnosed each year and around 25% of these are thought to have a genetic cause.
“Unlike breast cancer, relatively few high-risk prostate cancer genes have been established to date,” commented lead author Jeffrey Smith, associate professor of at Vanderbilt, in a press statement.
“Inherited risk of prostate cancer is roughly twice that of breast cancer, but its genetic complexity is also considerably greater; this has been a formidable obstacle for global studies,” he added.
Other high-risk prostate cancer-linked genes include BRCA2 and HOXB13 where cancer-linked gene variants can increase risk by up to eightfold and threefold, respectively.
“WNT9B shares an unexpected commonality with the previously established prostate cancer risk genes HOXB13 and HNF1B: they are each required for embryonic prostate development,” noted the authors.
The study documented several variants in WNT9B. E152K, which increased risk by 2.5-fold and reached significance in the multi-biobank meta-analysis included around 500,000 people. Another variant, WNT9B Q47R had genome-wide significance in the Finnish population tested.
Two other genes, KMT2D and DHCR7, also had a smaller association with prostate cancer in the larger meta-analyses.
It is important to know about genetic variants that predispose to cancer as the person in question can then be given extra testing and early screening to improve outcomes if cancer is detected.
“Risk for prostate cancer due to pathogenic WNT9B mutation is comparable to risk of breast cancer conferred by pathogenic mutations that are routinely tested for breast cancer care,” Smith said.
“Knowledge of inherited mutations can guide selection of effective treatments and can carry broader implications for a family.”
The researchers now want to assess if mutations in WNT9B could influence clinical outcomes for these patients. For example, assessing if precision therapies could be useful for these individuals.
