Study Reveals New Genetic Markers Linked to Increased Prostate Cancer Risk
A recent study published in JCO Precision Oncology has identified pathogenic variants in the WNT9B gene and other genes associated with genitourinary development, linking them to an increased risk of prostate cancer in men with a family history of the disease.
Jeffrey R. Smith, MD, PhD
Inherited Risk and Genetic Complexity
Jeffrey R. Smith, MD, PhD, the senior author of the study and an associate professor of medicine in the Division of Genetic Medicine at Vanderbilt University Medical Center, highlighted the challenges in identifying high-risk genes for prostate cancer. “Unlike breast cancer, where several high-risk genes have been established, it has been difficult to pinpoint similar markers for prostate cancer,” Smith explained. “The inherited risk of prostate cancer is roughly double that of breast cancer, yet its genetic landscape is far more intricate, making it a significant hurdle for researchers.”
The Role of WNT9B Gene Mutations
The study, conducted across four independent biobanks, explored the connection between WNT9B gene mutations and prostate cancer risk. Utilizing a case-control comparative design and genome-wide single-allele and identity-by-descent analytic methods, scientists consistently found a link between WNT9B gene mutations and an increased risk of prostate cancer. The risk ranged from a two-to-12-fold increase across all four studies.
Specific Variants and Their Impact
One particular variant, WNT9B E152K, was found to elevate the risk of prostate cancer by 2.5 times and reached genome-wide significance in the meta-analysis. This assessment encompassed a half million patients, further validating the findings.
Another variant, WNT9B Q47R, also showed a significant risk association in a Finnish population. The identify-by-descent analysis confirmed a founder effect, indicating that this variant may have originated from a single ancestor.
Other Genes Involved in Genitourinary Development
The researchers extended their investigation to two additional genes, KMT2D and DHCR7, both of which are known to cause Mendelian genitourinary defects. While the meta-analysis indicated nominal associations with an increased risk of prostate cancer, their clinical significance requires further exploration.
Implications and Future Directions
Smith underscored the importance of these genetic discoveries, stating, “Risk for prostate cancer due to pathogenic WNT9B mutation is comparable to the risk of breast cancer conferred by mutations commonly tested in breast cancer screening. Understanding these genetic markers can help in selecting effective treatments and has broader implications for potential familial screening.”
The next phase of this research aims to determine whether these gene mutations influence clinical outcomes, potentially leading to personalized approaches to cancer management and prevention.
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