A study led by Vanderbilt University Medical Center has identified a gene mutation. It increases the risk of developing prostate cancer, marking a significant step in understanding inherited forms of the disease. The research, published in JCO Precision Oncology, found that mutations in the WNT9B gene. It is normally active during embryonic prostate development—raise the likelihood of prostate cancer in adulthood.
A Major Genetic Breakthrough in Prostate Cancer Research
The study’s findings were confirmed across five independent populations, collectively analyzing data from 500,000 U.S. and European patients. According to lead author Jeffrey Smith, MD, PhD, an associate professor of Medicine in the Division of Genetic Medicine, men carrying the WNT9B mutation face a two- to twelve-fold increase in prostate cancer risk compared to those without the mutation.
“Unlike breast cancer, relatively few high-risk prostate cancer genes have been established to date,” Smith said. “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.”
A pathogenic gene mutation—a change in a gene’s DNA sequence. It can either be inherited from a parent or occur spontaneously over a lifetime. The discovery of WNT9B as a high-risk gene places it alongside HOXB13, the 8q24 locus, and BRCA2 as key genetic markers for prostate cancer susceptibility.
Gene Mutation Parallel to Breast Cancer Genetics
The study suggests that prostate cancer risk associated with the WNT9B mutation is comparable to the risk of breast cancer. It may be linked to BRCA mutations, which are routinely screened for in breast cancer patients. Smith emphasized the importance of identifying inherited mutations in prostate cancer, as such knowledge can help guide targeted treatments and inform screening strategies for at-risk individuals and their families.
“Knowledge of inherited mutations can guide the selection of effective treatments and carry broader implications for a family,” Smith explained.
Future Research and Clinical Implications
The discovery raises important questions about whether inherited genetic mutations influence treatment outcomes, prompting researchers to explore precision medicine approaches for prostate cancer patients. Future studies will examine whether an inherited or acquired WNT9B mutation affects the disease’s progression or response to therapy.
Grants from the Veterans Health Administration, the V Foundation for Cancer Research, and the National Institutes of Health supported the research. Data for the study was drawn from the Million Veteran Program, an initiative of the Veterans Health Administration focused on understanding genetic and environmental influences on disease.
With prostate cancer being one of the most common cancers in men, this breakthrough may pave the way for genetic testing and tailored treatment strategies that could improve early detection and survival rates for those at the highest risk.
Reference: William D. Dupont, Angela L. Jones, Jeffrey R. Smith. Coding Variants of the Genitourinary Development Gene WNT9B Carry High Risk for Prostate Cancer. JCO Precision Oncology, 2025.
