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Genetic Risk Factor for Prostate Cancer Discovered

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May 9, 2006

CHICAGO --- Scientists from The Robert H. Lurie Comprehensive Cancer Center of Northwestern University participated in a discovery of a common genetic variant that predisposes men to prostate cancer. The gene discovery is described in a study in the online edition of Nature Genetics and will appear in the journal's June print edition.

The gene variant was discovered by the deCODE genetics Company in Iceland and was confirmed in several cohorts, including nearly 460 patient tumor samples contributed by William J. Catalona, M.D., from the Prostate Cancer Specialized Program of Research Excellence (SPORE) at the Cancer Center.

Catalona is professor of urology at Northwestern University Feinberg School of Medicine and director of the Clinical Prostate Cancer Program at the Cancer Center.

The study on the prostate cancer susceptibility gene found that about 19 percent of men of European ancestry with prostate cancer carry at least one copy of the variant, which confers an approximately 60 percent increase in risk of the disease and accounts for approximately 8 percent of cases.

The gene variant confers roughly the same increase in risk among African Americans but is twice as common. The variant thus accounts for approximately 16 percent of prostate cancer among African American men and contributes to the higher incidence of the disease among African Americans.

This is one of the first genetic variants ever found to confer significant risk of a major cancer among the population in general. Most previously identified cancer genes have their effect on cancer risk only in families with a clear family history of cancer, or are only found mutated in tumors. This discovery is important from a medical standpoint because the only firmly established risk factors for the disease until now have been age, family history and ethnicity.

“As this variant also appears to be associated with the development of more aggressive prostate tumors, a diagnostic test for the variant may enable doctors to make more informed decisions as to how closely they should monitor those who are at high risk, and how aggressively they should treat the disease once it presents. We plan to use this discovery as the basis for the development of such a diagnostic test,” said Kari Stefansson, CEO of deCODE and senior author on the study.

The variant is located within a putative gene of unknown function in a region on chromosome 8 known to be one of the most frequently amplified chromosomal regions in prostate tumors.

Catalona and other researchers in Northwestern's prostate cancer SPORE are now working with deCODE genetics to use frozen tumor sample from carriers of the genetic variant to perform functional studies to determine how they could cause aggressive prostate cancer.

The total number of patient and control samples analyzed in the study was 3,430 and 2,675, respectively. In addition to the Northwestern Prostate Cancer SPORE, other cohorts included the Icelandic Cancer Registry; CAPS1, a population-based study of prostate cancer patients in Sweden; and the Flint Men's Health Study and the Prostate Cancer Genetics Project, both of the University of Michigan.

Prostate cancer is the most common non-skin cancer in men in the industrial world, and is responsible for nearly 30,000 deaths a year -- more any other cancer in men except lung cancer. The National Cancer Institute estimates that about 235,000 new cases of prostate cancer will be diagnosed in 2006. Prostate cancer develops most frequently in those older than 50 years.

The Cancer Center's  $11.4 million SPORE grant from the National Cancer Institute is directed at the prevention, early detection and treatment of prostate cancer. This prestigious grant makes Northwestern one of only 11 prostate cancer SPORE centers in the United States and the only prostate cancer SPORE grant recipient in Illinois.

The principal investigator on the prostate cancer SPORE grant is Chung Lee, John T. Grayhack Professor of Urology and professor of cell and molecular biology. Lee's research focuses on the cellular and molecular mechanisms of growth of the normal and cancerous prostate.