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Simple Test Can ID Men With Genetic Risk Factors for Prostate Cancer

Simple Test Can ID Men With Genetic Risk Factors for Prostate Cancer

Junho 17, 2015

SAN FRANCISCO -- June 17, 2015 -- Men with an elevated, genetically inherited risk for prostate cancer could be routinely identified with a simple blood or urine test, according to a study published early online ahead of the print edition of the journal Cancer Discovery.

The study analysed genetic samples and health records from more than 100,000 volunteers, making it one of the largest research projects in the United States to examine the genetic, health, and environmental factors that influence common diseases such as prostate cancer.

The researchers modelled prostate cancer risk using 105 specific bits of DNA that commonly vary among individuals and that they confirmed are associated with prostate cancer risk.

While the researchers estimated that each of these genetic variants only modestly alters risk, they determined that men with combinations of these DNA variants that placed them among the highest 10% for risk were more than 6 times as likely to be diagnosed with prostate cancer compared with the men who ranked among the lowest 10% for prostate cancer risk.

“We developed a risk model that may have clinical value,” said John Witte, PhD, University of California - San Francisco, San Francisco, California. “We also showed that there remain substantial undiscovered genetic risk factors for prostate cancer.”

Men ranked in the highest percentiles for risk in the study have a prostate cancer risk comparable with the breast cancer risk among women with BRCA1 or BRCA2 gene mutations, said Dr. Witte. While women suspected of having mutated BRCA genes can choose to undergo commercially available genetic testing, there currently is no routinely available clinical test to measure genetic risk for prostate cancer.

Screening strategies for prostate cancer are in flux. Measuring blood levels of prostate-specific antigen (PSA) began in the 1980s, but no longer is routinely recommended. Although cancers have been identified at earlier stages with this strategy, many prostate tumours identified with this approach never cause any harm, even without treatment.

Van Den Eeden, MD, Kaiser Permanente, Oakland, California, emphasised that the group also is trying to identify specific genetic risk factors that, when combined with other measures such as elevated PSA, could improve diagnosis prior to any referrals for invasive biopsies, and that might also point to the most aggressive cases of cancer.

“Now we are focusing on men with prostate cancer in this cohort who relapse despite treatment, and on those initially diagnosed with the most advanced disease, with the hope of identifying inherited combinations of genetic variations associated with the most aggressive, life-threatening cancers,” said Dr. Van Den Eeden.

The results point to the potential for large data sets such as this to lead to more precise diagnostics, one of several aspects of what is known as precision medicine.

The researchers also identified two new risk factors that previous studies had missed, each of which is associated with a nearly 20% increase in prostate cancer risk. One of the newly discovered risk factors -- identified by the addition of just 1 DNA base pair at a specific location on chromosome 6 -- is found in about 30% of the population, yet had never been detected in previous studies of tens of thousands of men. This single-base-pair DNA addition may affect the production of proteins believed by some scientists to be associated with prostate cancer. Such small deletions or insertions have been ignored in many studies, but Dr. Witte said that with new methods, they now can more easily be studied.

SOURCE: University of California - San Francisco

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Junho 2015