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Scientists identify susceptibility gene for prostate cancer on chromosome 17
Charles W. Schmidt

In the last several years, scientists have undertaken a search for the genetic basis of prostate cancer, a leading cause of death in men. Until recently, these investigations turned up few leads, making it difficult to ascertain the direction in which future research efforts should go. Now, scientists report they have identified a gene that is apparently linked to both high and moderate prostate cancer risk. Researchers identified the gene, ELAC2, first by scanning the genomes of 127 families in Utah with a history of the disease. A team from Myriad Genetics, Inc., of Salt Lake City, and the University of Utah then used the technique known as positional cloning to narrow the range and pinpoint the gene.

Two mutations in ELAC2 increased the risk for disease among the sample population 5-to-10 fold, according to Sudhir Sahasrabudhe, of Myriad Genetics. Furthermore, two variants of ELAC2 were associated with a moderate increase in risk (1.5-to-3 fold). "These results identify an important marker for genetic susceptibility to prostate cancer," says Sahasrabudhe.

The high-risk mutations were found in just two of the families studied, according to results published in the current issue of Nature Genetics. The variants for moderate risk, on the other hand, were more widely distributed among the study cohort. Sean Tavtigian, who led the study, says that mutations of ELAC2 likely account for a small fraction of all prostate cancer cases, and suggests that up to 20 or even 30 other genes may confer moderate susceptibility to the disease. But these preliminary findings, he says, argue for a large study investigating the influence of the mutation in a broader population.

In a News and Views piece entitled "Prostate cancer: simplicity to complexity," Mette Peters and Elaine Ostrander conclude that the consistency of the study's results point favorably to the relevance of ELAC2. "Given these provocative results and the large number of prostate-cancer families and cohorts under investigation, more data on this very interesting gene should be available in the near future," they write.

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Tavtigian, S.V. et al. A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genetics 27, 172-180 (February 2001).
Peters, M.A., Ostrander, E.A. Prostate Cancer: simplicity to complexity. Nat Genetics 27, 134-135 (February 2001).

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