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Gene Mix Raises Probability Of Prostate Cancer, Study Says

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By MARILYNN MARCHIONE, The Associated Press

Published: January 17, 2008

Scientists have taken a key step toward revealing the causes of prostate cancer, finding that a combination of five gene variants dramatically raises the risk of the disease. Added to family history, they accounted for nearly half of all cases in a study of Swedish men.

The discovery is remarkable not just for the big portion of cases it might explain, but also because this relatively new approach - looking at combos rather than single genes - might help solve the mystery of complex diseases such as cancer and diabetes that are thought to involve multiple genes or interactions between them.

"It gives us a new way of looking at genetic risk factors," said Teri Manolio of the National Human Genome Research Institute, the federal agency focused on such work.

It also might lead to a blood test to predict who is likely to develop prostate cancer.

The Swedish results must be verified in other countries and races, where the gene variants, or markers, may not be as common. Researchers have plans to look for them in U.S. men.

An 'Eyebrow-Raising Study'

Unfortunately, the markers do not help doctors tell which cancers need treatment and which do not.

Nor did they correlate with levels of PSA, a blood substance often used to gauge cancer risk. PSA is a notoriously imprecise measure, so a gene test that independently predicts risk would be valuable, experts said.

This "eyebrow-raising study" should quickly spur more research, particularly in blacks, who have a higher incidence of prostate cancer, said Howard Sandler, a cancer specialist at the University of Michigan and spokesman for the American Society of Clinical Oncology.

The study was led by doctors at Wake Forest University in Winston-Salem, N.C., and involved Johns Hopkins University in Baltimore and the Karolinska Institute in Stockholm. Results were published online Wednesday by the New England Journal of Medicine.

A Mysterious Disease

Prostate cancer is the most common cancer in American men and arguably the most mysterious. Unlike breast cancer, where variants in single genes are known to confer greater risk, few have been discovered for prostate cancer. In the past year, other researchers identified five, but none individually seemed to raise risk very much.

Combinations of them did, the new work reveals.

The study involved 2,893 men with prostate cancer and 1,781 similar men who did not have the disease. Sweden was chosen because the population is so ethnically similar and well suited to gene studies.

When family history was added in, men with five of the six factors were more than nine times more likely to develop the disease. The six factors accounted for 46 percent of prostate cancer cases in the study.

"That is a lot," Manolio said, but added, "you have to take those estimates with a grain of salt" because less than 2 percent of men had all of the variants.

How Will Information Be Used?

Still, some are very common - one is estimated to occur in 60 percent of men.

Government and cancer groups in the United States and Sweden funded the work. Some of the U.S. researchers are seeking patents to develop a blood test using the results.

"It's the boutique medicine of the future," said Peter C. Albertsen, a surgery professor and prostate cancer specialist at the University of Connecticut. "We can know what diseases we will have to face in the rest of our lives."

That worries him, as it does Edward P. Gelmann, deputy director of the Comprehensive Cancer Center at Columbia University.

"Technology today enables us to find out a huge amount of information," Gelmann said. "But how does the public deal with this information? How does it help them make decisions? And if they make a decision, does that lead to a day, a week, a month of life saved?"

Information from The New York Times was used in this report.

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