New York Health News

(AP) 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 -- may help
solve the mystery of many complex diseases like 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 Dr. 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. These men could be closely monitored and
perhaps offered hormone-blocking drugs like finasteride to try to
prevent the disease.

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

Unfortunately, the markers do not help doctors tell which
cancers need treatment and which do not -- they turned out to have
nothing to do with the aggressiveness of a tumor, only whether a
man is likely to develop one.

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
very valuable, experts said.

This "eyebrow-raising study" should quickly spur more
research, particularly in blacks, who have a higher incidence of
prostate cancer, said Dr. 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.
Prostate cancer is the most common cancer in American men and
arguably the most mysterious. Unlike breast cancer, where variants
in single genes like BRCA 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.
It 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.

Researchers looked for "hot spots" of differences in genes of
the men with cancer compared to the others, then focused on the
five most common variants, which were single letter changes in the
gene's usual DNA alphabet.

When four or five variants were present, men were more than four
times more likely to develop prostate cancer than those with none
of the markers.

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

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

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

However, scientists must prove that any such blood test does not
give too many false alarms, Dr. Edward Gelmann of Columbia
University Medical Center writes in an editorial. In the Swedish
study, 2 percent of the men without prostate cancer had four of the
five gene variants purported to raise risk.

Until more is known, men should talk with their families about
any history of prostate cancer, Sandler and Manolio suggested.
The U.S. Surgeon General and various federal health agencies
recently launched the U.S. Surgeon General's Family History
Initiative to encourage people to learn more about their family
health history. A Web site for the project gives families an
Internet tool and advice on how to track this information

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