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More Gene Variations Found That Raise Prostate Cancer Risk
Date:2/11/2008

Some variants increase chances of disease up to 60%, researcher says

MONDAY, Feb. 11 (HealthDay News) -- Scientists have uncovered at least 10 new genetic variations associated with an increased risk for prostate cancer.

The new findings double the number of genetic variants that are known to be associated with prostate cancer. Three reports detail the discoveries in the Feb. 10 online edition of Nature Genetics.

"Predisposition to prostate cancer, at least in part, is due to variations in a person's genetic code," said Dr. Rosalind Eeles, a Reader in Clinical Cancer Genetics in The Institute of Cancer Research, in Sutton, U.K., and lead author of one of the reports.

"There are many variants in the genome which confer prostate cancer risk, and these results move us nearer to being able to develop a profile of genetic variation which predicts for increased risk of the disease. This will enable us to target screening, prevention strategies and treatment," she said.

Each of the three reports was done by a different group, one in the United States, one in Great Britain, and one in Iceland. Each group studied thousands of men with and without prostate cancer.

In the first report, Eeles, and her colleagues identified seven genetic variances that were associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X.

"We have studied hundreds of thousands of genetic variants in over 10,000 men both with and without prostate cancer," Eeles said. "We have found seven new sites in the human genome that are linked to men's risk of developing prostate cancer."

Among these new sites is one gene called MSMB which could possibly be used in screening for prostate cancer and disease monitoring, Eeles noted. "Another of the sites harbors a gene called LMTK2, which might be a target for new treatments. These newly identified genetic alterations are present in over half of all prostate cancer cases. They each increase a person's risk of the disease by up to 60 percent."

In the second report, Dr. Stephen Chanock, head of the Genomic Variation Section at the U.S. National Cancer Institute, and his colleagues found genes associated with prostate cancer on chromosomes 7, 10 and 11, as well as nine other gene locations that are suggestive of an association with prostate cancer.

"We are finding the places in the genome that are associated with the risk for prostate cancer," Chanock said. "The reason this is so important is that prostate cancer is a complex disease and is not due to one genetic defect or one environmental exposure," he said.

Similar findings are being reported with breast cancer, colon cancer and lung cancer, Chanock said. "The same thing is happening in other diseases, such as diabetes, heart disease and stroke," he said. "Most diseases are complex and associated with multiple genes."

Exactly how each of these genes contributes to the risk for prostate cancer isn't clear, Chanock said. "Some of them may be responsive to environmental triggers, such as what you eat or what you inhale," he said. "Somewhere down the line, these findings may be clinically relevant, but it's too early to do that, because we are still discovering more."

In the third report, Julius Gudmundsson's team from deCODE Genetics Corp. in Iceland, found genes associated risk of prostate cancer on chromosomes 2 and X.

Although most of the gene variants are associated with a moderate risk, they are common in the population. Some of these variants are linked to more than less aggressive disease, Gudmundsson's team noted.

A substantial number of men have many risk variants that together confer clinically significant risk. In fact, 10 percent of men are at twice the risk and 1 percent of men are at three times the risk of developing the disease in the general population, Gudmundsson's group said.

One expert thinks these papers add to the general knowledge about prostate cancer's genetic underpinnings. However, how this will be translated into clinical practice is still unknown.

"These papers are adding a little bit to our knowledge of prostate cancer in the genome," said Dr. Durado Brooks, director of prostate and colorectal cancers at the American Cancer Society.

Brooks thinks the Gudmundsson paper is important, because it shows a link between genes and aggressive prostate cancer. "This is the sort of information that has the potential to be most useful in a clinical setting," he said.

Identifying which men are at risk for developing aggressive prostate cancer will be important in terms of offering care and not over treating men whose prostate cancer is less aggressive, Brooks said. "The ability to identify aggressive tumors is likely to be a great benefit," he said.

In addition, Brooks thinks that genetic information will help find ways to modify the risk of developing prostate cancer. This could involve medication and/or lifestyle changes, he said.

"This knowledge could also lead to better diagnosis and treatment," Brooks said.

More information

For more on prostate cancer, visit the U.S. National Cancer Institute.



SOURCES: Stephen Chanock, M.D., head, Genomic Variation Section, U.S. National Cancer Institute, Bethesda, Md.; Rosalind Eeles, M.D., Ph.D., Reader, Clinical Cancer Genetics, The Institute of Cancer Research, Sutton, U.K.; Durado Brooks, M.D., director, prostate and colorectal cancers, American Cancer Society, Atlanta; Feb. 10, 2008, Nature Genetics, online


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