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Study Finds that Blood Test Can Gauge Prostate Cancer Risk

WINSTON-SALEM, N.C. – New genomics research has found that a simple blood test can determine which men are likely to develop prostate cancer. Researchers at Wake Forest University School of Medicine and colleagues found that five genetic variants previously associated with prostate cancer risk have a strong cumulative effect.

Reporting in New England Journal of Medicine, researchers found that a man with four of the five variants has an increased risk of 400 to 500 percent compared to men with none of the variants. The researchers then added a family history of prostate cancer to the equation – for a total of six risk factors. A man with at least five of the six factors had increased risk of more than 900 percent.
The article was published “Online First” today (Jan. 16) and will be included in the Feb. 28 print issue.
The scientists say each variant was independently associated with prostate cancer risk and that the variants are fairly common in the population. Together, these five variants and a family history accounted for almost half (46 percent) of prostate cancer patients. The study involved analyzing DNA samples from 2,893 men with prostate cancer and 1,781 healthy individuals of similar ages – all participants of a prostate cancer study in Sweden.
“This is significant and could affect clinical care,” said senior researcher Jianfeng Xu, M.D., Dr. PH., professor of epidemiology and cancer biology. “The information could substantially improve physicians’ ability to assess risk and determine the need for more aggressive screening or even a biopsy.”
For example, the test may be especially useful in men with a family history of prostate cancer or those who have a marginally elevated PSA (prostate specific antigen), he said.
The study is also important because it is one of the first to illustrate how a combination of several genes can affect risk of disease. Genomics teams nationwide are currently searching for combinations of genes that may underlie common diseases such as cancer, diabetes and asthma.
Currently, age, race and family history are the three factors associated with increased risk of prostate cancer. Family history is believed to account for about 10 percent of prostate cancer cases. Strikingly, researchers estimated that the five variants combined could account for about 40 percent of cases.
“Our finding provides an opportunity to supplement the well-established risk factors by looking at how many of these variants a man has inherited,” said Xu. “It may provide a much better weapon to guide clinicians.”
Until last year, no specific genetic variants had been consistently identified as markers for prostate cancer risk. Then, advances in technology allowed researchers to take a more systematic approach to looking at the entire genome. Instead of solely studying genes that they suspected were related to disease susceptibility, they could study the entire genome and look for associations.
Through these searches, several research teams identified five genetic locations associated with risk of developing prostate cancer: three on chromosome 8q24, one on chromosome 17q12 and one on 17q24.3.
Each variant alone was associated with moderate risk, but the effect wasn’t considered significant enough to justify testing individuals. The current study was the first to evaluate whether there is a cumulative effect from having multiple variants.
“When we considered the variants together we discovered their potential for predicting individual risk,” said Xu. “Because of the cumulative effects of these risk variants and family history, for the first time associations found through genome-wide screening appear to be useful in clinical practice.”
The researchers said further study is needed to determine how their findings of genetic testing may complement PSA (prostate-specific antigen) testing. The researchers found that the risk associated with the genetic variants is independent of PSA results.
“This suggests that a subset of men deemed to have a low risk of prostate cancer based on their PSA levels may in fact be at significantly elevated risk due to inheriting one or more of the genetic variants,” said S. Lilly Zheng, M.D., associate professor of internal medicine and the first author of the paper.
Genetic testing of these five variants will soon be offered at a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory at Wake Forest University School of Medicine. For more information, visit the website www.ProactiveGenomics.com or call 866-487-2344.
Co-researchers include senior author Henrik Gronberg, M.D., Ph.D. professor at the Karolinska Institutet in Stockholm, Sweden, and William B. Isaacs, Ph.D, professor at Johns Hopkins Medical Institutions in Baltimore, Md.

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Media Contacts: Karen Richardson, krchrdsn@wfubmc.edu, or Shannon Koontz, shkoontz@wfubmc.edu, 336-716-4587.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

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