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Combo Test Identifies Prostate Cancer Risk

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Over the past few years, scientists have identified several genetic markers — distinctive little stretches of DNA — that indicate a higher risk of prostate cancer.

That was interesting, but not particularly useful. A man's risk having just one of these markers isn't much higher, only 10, 20 or 30 percent.

A new study published online by the New England Journal of Medicine suggests the possibility of a genetic test that does much better. The new study looked at the combined effect of a handful of genetic markers on prostate cancer risk among 4,700 Swedish men.

"We were able to demonstrate by adding five different markers as well as family history that there's a tremendous additive effect," says Dr. Karim Kader, a Wake Forest University urologist and a study co-author.

Kader says men with all five markers plus a family history of prostate cancer have nearly a ten-fold increased risk of being diagnosed with prostate cancer.

That's a meaningful difference. So the researchers, in concert with a biotech startup company, have applied for a patent and are working on a marketable blood test that would tell a man whether he's at high risk of prostate cancer.

They say preliminary evidence suggests that the genetic markers they used in the study of Swedish men are found in African-American men, who have about twice the overall risk of prostate cancer as caucasians. But they say more work needs to be done to validate the test in the U.S. population.

Co-author William Isaacs of Johns Hopkins University thinks it won't take long to develop a commercially marketable test.

"One aspect of it may be to identify individuals at risk for the disease at some earlier stage of their lives, in their 20s or 30s," Isaacs says. "You may want to screen those men earlier and more intensively" for high levels of prostate-specific antigen, or PSA, the existing screening test for pre-symptomatic prostate cancer.

Men who don't have a positive genetic marker test might be safe to wait until later in life to get PSAs, Isaacs suggests.

But there are problems. Kader says the known genetic markers don't signal what doctors would most like to know about a man's prostate cancer risk.

"It's not aggressive or less-aggressive," Kader says. The test is "predictive of your risk of developing prostate cancer, period."

Dr. Howard Sandler of the University of Michigan, a prostate cancer spokesman for the American Society of Clinical Oncology, says that's the same problem doctors have with PSA tests.

"We can find lots of prostate cancer with PSA screening," Sandler says. "But what's really important is to identify those patients who really need to be treated for their prostate cancer."

Uncertainty over that question is leading to unnecessary biopsies, surgery and radiation therapy. It's what the experts call "overtreatment."

"Overtreatment is common in prostate cancer populations," Sandler says, "because prostate cancer can grow so slowly that it might never interfere with someone's life expectancy."

Kader, the Wake Forest urologist, says the planned genetic test "most definitely" will increase overtreatment of indolent tumors that may never cause men any trouble.

"But I'm not going to bury my head in the sand and disregard early prostate cancer diagnosis just for fear of diagnosing indolent disease," Kader says.

But Dr. Edward Gelmann of Columbia University isn't convinced that the multi-marker genetic test will be useful.

"We are a society of the worried well," Gelmann says. "People want as much information as they can get, and they will pay for it. Interpreting it is another matter.

"If I had a strong family history of prostate cancer, I would be checking my PSA starting at age 50 anyway," he adds. "If I did these tests and they indicated that my risk was stronger yet, what would I do differently?"

It's an example of a growing problem. Scientists are getting more information about genetic risk than doctors know what to do with.



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