DNA Variations Tied to Prostate Cancer Risk

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prostate cancerScientists have pinpointed a set of common variations in human DNA that signal a higher risk for prostate cancer in men who carry them. Some of these variations are more common in African-American men, which may help explain why prostate cancer rates are higher in African Americans than in men of other races.

The findings, published in 3 separate studies, may lead to genetic tests that will help identify those most at risk for the disease. The findings may also help unlock the biological mysteries behind prostate cancer, which could speed up the discovery of new treatments.

The 3 studies focus on DNA variations located on chromosome 8 in some men. The variations may be linked to as many as 68% of prostate cancer cases in African Americans, 60% in Japanese Americans, 46% in Latinos, 45% in native Hawaiians and 32% in whites, the authors of 1 of the studies calculate.

That study was performed by a 26-member research team led by investigators from the Keck School of Medicine at the University of Southern California in Los Angeles and from Harvard Medical School in Boston. A separate study was performed by researchers at the US National Cancer Institute and the American Cancer Society, and a third was led by scientists at deCODE Genetics Inc., an Icelandic biotech company.

All the studies appear in the online edition of the journal Nature Genetics.

"Building on this finding we may be able to identify men at highest risk for prostate cancer, diagnose the disease earlier, and hopefully prevent it all together," says John Niederhuber, MD, director of the National Cancer Institute.

Prostate cancer is the most common cancer in US men, other than skin cancer; in 2007 an estimated 218,890 men will be diagnosed with the disease and 27,050 men will die of it. A blood test for PSA (prostate-specific antigen, a substance made only by the prostate gland) can often find the disease early, but the test isn't always accurate. Some men with a normal PSA level may have cancer, and some men with a high PSA may have a different condition that isn't cancer.

To know for sure, men have to get a prostate biopsy, which is a potentially painful and expensive procedure. Doctors hope to find DNA variations that would help determine which men might need aggressive prostate cancer screening -- which could lead to biopsies -- because they have a high risk of developing the disease.

In the Nature Genetics studies, 8 variants were identified on chromosome 8, in a string of human DNA called the 8q24 region. Each variant was shown to help predict prostate cancer risk, with the predictive strength varying widely from 11% to 68% depending on race and other factors men inherit from their family.

Of the 8 variants, 6 were newly discovered, and 2 confirmed from earlier findings, the authors report. The 3 studies were based on genetic tests on thousands of men from many countries and backgrounds, with the Keck School of Medicine and Harvard Medical School research team looking at the largest group: more than 7,500 African-American, Japanese-American, native Hawaiian, Latino, and white men with and without prostate cancer.

The group from deCODE Genetics has been looking at prostate cancer markers on chromosome 8 for years, and expects to release a genetic screening test for the disease sometime in early 2008, says a company executive.

NCI's Niederhuber says the findings are important beyond their potential for new tests. The 8q24 region is nowhere near any known genes, so more work is needed to see if the heightened prostate cancer risk comes from the variant itself, or from other DNA segments along chromosome 8.

Inherited DNA changes are known to contribute to about 5% to 10% of all cases of the disease.

Citation: 'Multiple regions within 8q24 independently affect risk for prostate cancer.' Published online April 1, 2007, in Nature Genetics. First author: Christopher A. Haiman, Keck School of Medicine, Los Angeles.

Citation: 'Genome-wide association study of prostate cancer identifies a second risk locus at 8q24.' Published online April 1, 2007, in Nature Genetics. First author: Meredith Yeager, National Cancer Institute, Frederick, Maryland.

Citation: 'Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.' Published online April 1,2007, in Nature Genetics. First author: Julius Gudmundsson, deCODE Genetics, Reykjavik, Iceland.

Copyright © 2007 ACS News Today

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