January 30, 2001
Inherited prostate cancer gene identified
An international team of scientists has identified a gene that leads to inherited prostate cancer. The study, conducted by 43 scientists in the United States and Canada, is published in the February issue of the scientific journal Nature Genetics.
The research team was led by: Dr. Sean Tavtigian, Myriad Genetics Inc., Salt Lake City, Utah; Dr. Lisa Cannon-Albright from the University of Utah; Dr. Johanna Rommens, The Hospital for Sick Children (SickKids) in Toronto; and Dr. Jacques Simard of Laval University in Quebec City.
"Because numerous genes and environmental factors, including a high-fat diet, appear to play a role in prostate cancer, the various forms of the gene are probably responsible for only two to five per cent of all cases of the disease," said Dr. Tavtigian, director of Cancer Research at Myriad Genetics.
Dr. 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 are.
Two different types of changes were found in the gene - named ELAC2 and also called HPC2. In a small number of families, changes were found that would eliminate the gene product, resulting in a high risk of developing prostate cancer. In other cases, specific DNA sequence changes conferred a moderate risk.
"Ones genetic makeup is an important factor in prostate cancer, but tracking down the exact genes has been extremely difficult. The ELAC2 gene is first prostate cancer susceptibility gene that has been identified from family based studies. After the Utah group targeted a location on chromosome 17, my laboratory helped to identify the candidate genes in the target region," said Dr. Rommens, a senior scientist in the Genetics and Genomic Biology Program at The Hospital for Sick Children.
"This is a significant discovery because of the difficulty in identifying genes that contribute to complicated diseases caused by multiple genes and environmental factors. It is not yet practical to determine a genetic test that would be available immediately, but this study does provide a new starting point as this type of gene had not been previously implicated in prostate cancer," added Dr. Rommens, also an associate professor in the Department of Molecular and Medical Genetics at the University of Toronto.
Scientists do not yet understand ELAC2s 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 that it is central to biological function of normal cells in every multi-cellular organism.
The study culminates more than 10 years of work with Utah families at high risk of prostate cancer, and was funded by the pharmaceutical companies Schering-Plough Corp. and Endorecherche, the National Institutes of Health, the US National Cancer Institute and the state of Utah.
"I believe all common diseases have an underlying, inherited predisposition. 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. Thats going to result in less illness and death." said Dr. Cannon-Albright, a genetic epidemiologist at the University of Utah.
The Canadian Cancer Society estimates that 16,900 men in Canada were diagnosed with prostate cancer during 2000. It is estimated that 4,200 men died of prostate cancer in 2000, the second-leading cause of cancer deaths in Canadian men after lung cancer.
More than 70 per cent 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 per cent 20 years ago to 93 per cent today.
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