http://www.nyti mes.com/2008/01 … &hp&oref=slogin
$300 to Learn Risk of Cancer of the Prostate
By GINA KOLATA
A combination of common and minor variations in five regions of DNA can help predict a man’s risk of getting prostate cancer, researchers reported Wednesday.
A company formed by researchers at Wake Forest University School of Medicine is expected to make the test available in a few months, said Karen Richardson, a Wake Forest spokeswoman. It should cost less than $300.
This is, some medical experts say, a first taste of what is expected to be a revolution in medical prognostication. The results, they agree, are clear. But the question is what happens next. And will patients be helped or harmed? Because the new test — which will analyze DNA in blood or saliva samples and is to be offered by ProActive Genetics — cannot predict which men will get aggressive cancers, it could lead to more screening and unnecessary surgery and complications. But, proponents say, it could also help men decide whether they want aggressive screening in the first place.
The researchers found that about 90 percent of the men in the study had one or more of the gene variants and more than half had two or more. The cancer risk increased as the number of variants rose and increased substantially when men had four or five of the variants.
Men with four or five variants made up only 2 percent of the study population but had a 4.5-fold increased risk of having prostate cancer compared with men who had none of the variants. If the men also had a family history of prostate cancer, their risk was nearly 10 times higher than that of men with none of those risk factors. Less than 1 percent of the population had all the variants and a family history.
The researchers report that nearly half of the cases of prostate cancer among the roughly 5,000 men in the study could be attributed to the five gene regions and a family history, with some men having one or two of the gene variants and others having all five and a family history.
Prostate cancer becomes more common as men age — autopsies of elderly men find that most had prostate cancer, whether they knew it or not. But the men in this study had an average age of about 65, when the disease is less common and more likely to kill.
William B. Isaacs, a professor of urology and oncology at Johns Hopkins University and an author of the new report, said that if research validates what has been found, men may want to get the new genetic test when they are young, 35, say. Those at high risk because of their genetics might then choose to start prostate-cancer screening earlier than the usual age of about 50, using a blood test that looks for proteins secreted by prostate tumors.
“I think that makes sense,” said Dr. Howard Sandler, a professor of radiation oncology at the University of Michigan and a spokesman for the American Society of Clinical Oncology.
But others worry that more frequent testing could exacerbate what is already a major problem: most prostate cancers grow so slowly that they would have been harmless if left alone. But since doctors cannot tell which are dangerous, they treat nearly all that they find. And treatment has serious side effects, including, often, impotence and incontinence. Nonetheless, researchers say, the test is a harbinger of things to come.
“It’s the boutique medicine of the future,” said Dr. 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 Dr. 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,” Dr. 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?”
The study, by scientists at Wake Forest University School of Medicine, the Karolinska Institute in Sweden, the Harvard School of Public Health, and Johns Hopkins Medical Institutions, will appear in the Jan. 31 issue of The New England Journal of Medicine. It was released online on Wednesday, a journal spokeswoman said, because “it is a very active area of research with a lot of competition.”
Researchers long knew that the disease often runs in families. Though scientists spent years looking for genes, they found none that were reproducibly associated with a marked effect.
With new technology to scan the entire length of a person’s DNA, researchers tried a new approach. They began looking for small variations in tiny DNA regions that were associated with prostate cancer. That resulted in the discovery, by several groups of investigators in Iceland and the United States, of the gene variants, small alterations in gene sequences. Unlike traditional genetic links to disease, the variants are not mutations that destroy a gene’s function. In fact, no one knows what their effect is.
The next step was to ask whether those variants really could predict who had prostate cancer. So Dr. Jianfeng Xu, a professor of epidemiology and cancer biology at Wake Forest University School of Medicine, and his colleagues studied a Swedish population of 2,893 men with prostate cancer and 1,781 men who did not have it. That led to their finding that each of the five variants independently predicted prostate cancer risk.
“Each confers a moderate risk,” Dr. Xu said, adding that the effect of having just one of the variants — a 10 or 20 percent increase in a man’s chance of having prostate cancer — was not enough to justify using a single variant for screening. But, he added, because each conferred an independent risk, the risks added up so that the more men had, the greater their risk. Then they found that family history of the cancer added an independent risk. “That was very, very surprising to us,” Dr. Xu said.
The next step, Dr. Isaacs said, is to look in other populations. “We think that can happen almost instantaneously,” he said, explaining how scientists have blood samples and family histories of thousands of men who were tested for prostate cancer.
But some said that if the test leads to more screening, it is not necessarily a good thing. There is already too much prostate-cancer screening, they say, resulting in too much treatment. “To me, it is a nightmare,” Dr. Albertsen said. “We are just feeding off of this cancer phobia.”
What is needed, and what the new test does not provide, is a way to decide which cancers are dangerous and which are not, Dr. Isaacs said. Still, he said the new test could help patients if it was used with caution. “We may be premature with this idea — everyone has a different way of thinking about this — but it should not take five years to know if we are on the right track. All this can happen very rapidly.”
“We have worked with enough families that have a positive family history to know that people are anxious to know their risk of prostate cancer,” he said.
