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A genetic test developed by researchers at ӳ����ý Clinical Labs and the U.S. Department of Veterans Affairs (VA) is now enabling a large, nationwide clinical trial aimed at improving health care for men at increased risk of developing prostate cancer, the second-leading cause of cancer deaths in U.S. men. 

The test looks for hundreds of genetic changes across the genome that are linked to prostate cancer. The test costs much less than other genome analysis methods, making it cost-effective in clinical research settings such as this trial. Led by VA researchers, the trial will enroll 5,000 veterans from across the VA healthcare system nationally and explore whether the genetic test can help doctors detect prostate cancer earlier than existing screening methods and better identify men at high risk for developing the disease. 

Those deemed to be high-risk could benefit from enhanced screening to detect cancer earlier, while those at low risk could avoid unnecessary biopsies and other procedures. In a study published today in , the VA and ӳ����ý scientists describe the trial, which has already enrolled over 3,000 men from every US state and territory, and their efforts to develop and validate the genetic test.

“Prostate cancer is a huge concern and major health burden for VA's patient population, so it’s an ideal place to conduct this research,” said study senior author Jason Vassy, a physician-scientist with the VA Boston Healthcare System and Mass General Brigham, an associate professor of medicine at Harvard Medical School, and leader of the clinical trial, known as the Prostate Cancer, Genetic Risk, and Equitable Screening Study (). 

(BCL) developed the DNA sequencing approach that is enabling the genetic test. A growing number of healthcare and other organizations are partnering with BCL to use this approach, called the clinical blended genome-exome, to provide low-cost genetic testing for studies on a variety of diseases including heart disease and cancer. 

“The blended genome-exome is dollar for dollar one of the best value genetic tests you could get today, and we’re excited to see it power a variety of studies looking to accelerate the implementation of genomic medicine, which is core to the mission of ӳ����ý Clinical Labs,” said Niall Lennon, a study co-author and chief scientific officer and chair of BCL.

IMPROVING CARE

As a primary care physician at VA Boston Health Care, Vassy treats veterans — primarily middle-aged men or older who are the main demographic affected by prostate cancer. He explained that while the current gold standard for prostate cancer screening — the PSA blood test — can in some cases warn of a cancer that needs treatment, in others it may fail to detect cancer or even be a false alarm. 

Vassy knew that a better indicator could lie in DNA. Prostate cancer is one of the most heritable cancers, so he and his colleagues set out to build a better risk predictive model based on recently discovered genetic risk factors for the disease. They analyzed genetic, family history, and medical data on nearly 600,000 men from the Million Veterans Program, a VA biobank, and developed the Prostate CAncer integrated Risk Evaluation (P-CARE) model. 

After validating the P-CARE model in an external dataset, the researchers next wanted to create a blood test based on this model that they could evaluate in the clinic, so they connected with ӳ����ý Clinical Labs. BCL scientists had recently finalized a clinical-grade version of their blended genome-exome method, which reads the entire genome at several-fold lower cost than other sequencing approaches. 

ӳ����ý Clinical Labs scientists validated the P-CARE model using data on 74,000 individuals from the NIH’s All of Us Program. In the new study, the team showed that individuals who were predicted by the model to be in the highest-risk group had a several-fold greater chance of being diagnosed with prostate cancer, while those in the lowest-risk group were diagnosed much less often than average. 

The ӳ����ý team developed a workflow for generating genomic data and clinical reports for physicians that are now being used in Vassy’s clinical trial. 

Results from the trial could one day inform care for not only veterans, but for any man looking to evaluate their personal risk level and make informed choices about prostate cancer screening. 

Note: Jason Vassy is speaking in his personal capacity and not representing the Department of Veterans Affairs.