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Genetic Mutations Boost Prostate Cancer Risk
Date:1/16/2008

These variants plus a family history can increase risk up to tenfold, study suggests,,,,

WEDNESDAY, Jan. 16 (HealthDay News) -- A new blood test that looks at five genetic variants could one day predict the risk of developing prostate cancer, a new study says.

Researchers found that among men with four of the five variants, the risk of prostate cancer is increased 400 percent to 500 percent, compared to men with none of the variants. And if a man has these gene variants and a family history of prostate cancer, his risk of developing the disease increases more than 900 percent.

"There are five genetic variants that have been shown to be associated with prostate cancer risk," said lead researcher Dr. Jianfeng Xu, a professor of epidemiology and cancer biology at Wake Forest University School of Medicine.

For the study, the researchers examined DNA samples from 2,893 men with prostate cancer and compared them with DNA of 1,781 healthy men. All the men participated in a prostate cancer study in Sweden.

The researchers found that each of these common genetic variants was independently associated with prostate cancer risk. The five variants plus a family history of prostate cancer accounted for 46 percent of prostate cancer patients.

The effect of each variant is too small to be useful in predicting the risk for prostate cancer, Xu said. "But if you have four of these variants your risk is increased fourfold, which is something we have never seen before," he said.

The five genetic locations include three on chromosome 8q24, one on chromosome 17q12, and one on chromosome 17q24.3, according to the report, published online Jan. 16 in the New England Journal of Medicine.

When family history of prostate cancer is added to the mix, the results become more striking, Xu said. "Family history is the sixth factor," he said. "For a man with five gene variants and a family history the risk is increased tenfold."

Xu thinks that by using these gene variants and family history as a guide, "we can use this information to predict which men have a risk of developing prostate cancer."

Currently, age, race and family history are the three risk factors associated with increased risk of prostate cancer.

The researchers said the study is important because it's one of the first to show how a combination of several genes can affect disease risk. Genomics teams across the United States are looking for combinations of genes that may contribute to common diseases such as cancer, diabetes and asthma, according to background information for the study.

Dr. Durado Brooks, director of prostate and colorectal cancer at the American Cancer Society, said the findings are important, but it's not yet clear how they could be used in clinical practice.

"This study is helping us understand the role of genetic variants in the risk for prostate cancer," Brooks said.

But, he added, "If you develop a test and tell a man you have five times the risk of developing prostate cancer as other men, what do you do with that?"

Brooks also noted that these genetic variants don't indicate if the disease is aggressive and needs aggressive treatment, or if it's a slow-growing cancer that may not need immediate treatment.

"We still need to find markers of disease aggressiveness. We still need better treatments," he said.

Prostate cancer is the most common type of cancer in American men, other than skin cancer. It is the second leading cause of cancer death in men, behind lung cancer, according to the American Cancer Society.

The society estimates that there will be about 218,890 new cases of prostate cancer in the United States this year, and about 27,050 men will die of the disease.

More information

To learn more about prostate cancer, visit the U.S. National Cancer Institute.



SOURCES: Jianfeng Xu, M.D., Dr.PH., professor, public health and cancer biology, Wake Forest University School of Medicine, Winston-Salem, N.C.; Durado Brooks, M.D., director, prostate and colorectal cancer, American Cancer Society, Atlanta; Jan. 16, 2008, New England Journal of Medicine, online


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