UNIVERSITY OF UTAH MEDIA RELEASE
Embargoed by the journal Nature Genetics for release at 3 p.m. MST Tues. Jan. 30, 2001
Scientists Identify Prostate Cancer Susceptibility Gene;Gene Named ELAC2 May Account for 2 Percent to 5 Percent of All Cases
Contacts:--Lisa Cannon-Albright, University of Utah genetic epidemiologist - office (801) 587-9300, home (801) 277-8023, [email protected]--Sean Tavtigian, Myriad Genetics cancer research director - office (801) 584-3641, home (801) 359-9404. (Tavtigian will not be reachable until after 2:30 p.m. MST Jan. 30.)--Lee Siegel, University of Utah science writer - (801) 581-8993, cell (801) 244-5399, [email protected]--William A. Hockett, Myriad Genetics corporate communications - office (801) 584-3600,[email protected]
Jan. 29, 2001 - The first known gene to put men at high risk for developing prostate cancer has been identified in a newly published study by researchers at Myriad Genetics Inc., the University of Utah School of Medicine and LDS Hospital in Salt Lake City, and at two universities in Canada.
Because numerous genes and environmental factors - including a high-fat diet - appear to play a role in prostate cancer, various forms of the gene probably are responsible for only 2 percent to 5 percent of all cases of the disease, said Sean Tavtigian, vice president and cancer research director at Myriad Genetics.
Two mutations of the gene - named ELAC2 and also called HPC2 - place men who carry the mutant forms at high risk of developing the slow-growing cancer, while two other "variants" of the gene confer a moderate increase in prostate cancer risk.
The study, conducted by 43 scientists, was published in the February issue of the journal Nature Genetics. It details the discovery first announced last October when the American Society of Human Genetics met in Philadelphia.
The research team was led by Tavtigian (pronounced Tav-tig-yen); genetic epidemiologist Lisa Cannon-Albright and molecular geneticist Susan Neuhausen of the University of Utah's medical informatics department; Jacques Simard of Laval University in Quebec City; and Johanna Rommens of the University of Toronto. Cannon-Albright and another co-author also are affiliated with LDS Hospital.
Tavtigian expects that within five to 10 years, researchers will identify five more genes that mutate to place carriers at a high risk of getting prostate cancer, and perhaps 20 to 30 other genes that make men moderately susceptible to developing the disease. So far, ELAC2 is the only high-risk gene identified, although nine moderate-risk genes already have been pinpointed, he said.
Cannon-Albright, a genetic epidemiologist at the University of Utah, said the study culminates more than 10 years of work with Utah families at high risk of prostate cancer, and should help dispel pessimism about the difficulty of identifying genes that contribute to complicated diseases caused by multiple genes and environmental factors.
"I believe all common diseases have an underlying, inherited predisposition," she said. "Because there are other risk factors and multiple genes for common diseases, these types of genes are extremely difficult to find. But finding them is going to provide the key to earlier diagnosis and more appropriate treatment. That's going to result in less illness and death."
Although mutations and variants of the ELAC2 gene likely account for only a small proportion of prostate cancer cases, "identification of any gene involved in prostate cancer provides us with clues to move on to the next step," said Neuhausen, a University of Utah molecular geneticist. "It helps lead to better understanding of how the disease develops and of what other genes and environmental factors may be important."
The American Cancer Society estimates that 198,100 men in the United States will be diagnosed with prostate cancer during 2001. The group estimates prostate cancer will kill 31,500 men in the United States in 2001, making it the second-leading cause of cancer deaths in American men after lung cancer.
Studies indicate a strong inherited predisposition may be responsible for 5 percent to 10 percent of all prostate cancers. But Tavtigian said genes that pose a moderate risk of prostate cancer might account for another 20 percent to 40 percent of all cases.
To find the ELAC2 gene, the University of Utah researchers used the state cancer registry and the Utah Population Database to find families with greater-than-expected rates of prostate cancer. The university researchers sought volunteers from the families and collected blood samples. Myriad extracted DNA from the blood to study genetic material.
By studying 33 Utah families with excessive rates of prostate cancer, the researchers determined a gene on chromosome 17 conferred an inherited risk of developing prostate cancer. When the analysis was expanded to 127 high-risk Utah families, the researchers were able to identify the specific gene as ELAC2.
"In the general population, between 5 percent and 10 percent of men get prostate cancer by age 80," Tavtigian said. "In these families, up to 20 percent or 30 percent of the men get prostate cancer, and often at a younger age, primarily in the 50s and 60s."
However, when the researchers studied mutations of ELAC2, they found those mutations caused prostate cancer in only two of the families - and not even in all members of those families - consistent with the idea other genes and environmental factors cause many cases of prostate cancer. But two variant forms of the ELAC2 gene were present in most of the families, indicating those forms contribute to a moderately increased risk of prostate cancer for many more people.
Tavtigian said men who carry one of the high-risk ELAC2 mutations are five to 10 times more likely to get prostate cancer than other men. Men who carry the moderate-risk forms of the gene are 1.5 to three times more likely to get the disease than other men.
Because a relatively small percentage of men who get prostate cancer carry the forms of ELAC2 that contribute to the disease, it is not practical to develop a test just for that gene and use it on all men. But as researchers identify more genes that moderately or strongly raise the risk of prostate cancer, a test could be devised to detect all of those genes and predict which men are most susceptible, Tavtigian said.
Myriad - which sells tests to detect genetic susceptibilities to breast, ovarian and colon cancer - wants to "understand enough of the high-risk and moderate-risk prostate cancer genes that you can combine them into a test that would be medically valuable," he said.
Tavtigian said the research was funded by the pharmaceutical companies Schering-Plough Corp. and Endorecherche, the National Institutes of Health, the National Cancer Institute and the state of Utah. He said Schering-Plough ultimately wants to develop new drugs to combat prostate cancer. Understanding how the ELAC2 gene contributes to prostate cancer eventually could lead to drugs to block such cancer-causing effects, he added.
Scientists do not yet understand ELAC2's role in normal prostate function or how abnormal forms of the gene contribute to prostate cancer. But the fact the gene is found in all fungi, plants and animals suggests "it is absolutely central to biological function of normal cells in every multicellular organism," Tavtigian said.
More than 70 percent of all prostate cancers are diagnosed in men older than 65. Early diagnosis using the prostate-specific antigen (PSA) test and digital rectal exams means the five-year survival rate for men with prostate cancer has increased from 67 percent 20 years ago to 93 percent today.
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