Scientists a Step Closer to Finding Prostate Cancer Gene
Defying what some believed to be insurmountable odds, researchers have narrowed the search for a prostate cancer gene to one small corner of the human genetic blueprint, a finding that promises improved diagnosis, new treatments and better survival rates for this most common of male cancers.
An estimated 317,000 American men are diagnosed with prostate cancer each year and 40,000 die from it.
The localization of a gene that causes the disease in families, reported today in the journal Science, “provides the first strong evidence that specific genes for prostate cancer do exist,” said Dr. William Isaacs of the Johns Hopkins University School of Medicine.
And it is a major step toward finding those genes, perhaps within the next year, according to some researchers.
Researchers estimate that the new gene, called hereditary prostate cancer 1 (HPC1), causes about a third of all inherited cases of prostate cancer--a percentage remarkably similar to that caused by the first breast cancer gene identified in women. They believe that identifying it and understanding its function will shed new light on how non-inherited cases of the disease develop as well.
“Once we learn what it does, it may turn out that it is mutated in many other men as well,” said Judith C. Gasson, director of UCLA’s Jonsson Comprehensive Cancer Center.
But the greatest excitement about the discovery is simply the recognition that a prostate cancer susceptibility gene exists. Scientists believe that about 10% of all prostate cancer is inherited.
“When we began this project, it was like Columbus setting off across the Atlantic Ocean in boats and not knowing if he was going to find land or drop off the edge of the world,” said Dr. Francis Collins, director of the National Center for Human Genome Research, where most of the study was carried out. “Now we have land in sight.”
Researchers estimate that about one in every 500 American men carries the defective gene and that these men have a 90% chance of developing prostate cancer by age 85. “The ability to identify a quarter of a million men with this ticking time bomb will be very useful,” Collins said.
Identifying men at high risk should improve therapy by enabling physicians to monitor them for the onset of the disease. “What you want to do is detect it early enough to cure it surgically or with radiation before it spreads,” Collins said. “Being able to focus your resources on men at the highest risk should be very beneficial--and probably even economical.”
A better understanding of the genetics of prostate cancer will be especially valuable, according to Dr. Harmon Eyre, chief medical officer of the American Cancer Society, because “it is the most complex cancer problem in the country.”
Some types of prostate cancer are extremely aggressive and require immediate, intensive treatment, he noted, while others are relatively benign and can be ignored. Unfortunately, clinicians have no way to distinguish between the two.
“The way in which we are ultimately going to determine which are aggressive and which are not is to understand their genetic makeup,” Eyre said. “This is an opening step toward that goal.”
Many scientists doubted that it would be possible to isolate a prostate cancer gene, both because the disease is so common--one man in five will develop it if they live long enough--and because it develops so late in life. The commonness suggests many causes, while the late onset makes it difficult to assemble families for study, both of which render the search for a gene extremely difficult.
Nonetheless, the evidence of inheritance of prostate cancer “was so compelling that we felt it was worth the investment of time” to look for the gene, said molecular biologist Jeffrey M. Trent of the genome research center, senior author of the Science report.
Researchers from the center, Hopkins and Umea University in Sweden studied blood samples from 600 patients in 91 Swedish and American families with a history of prostate disease. In a little more than a year, they performed more than 200,000 DNA profiles on the samples in what Trent called “truly a Herculean effort.”
Their research led them to a short segment of Chromosome 1, one of the 23 pairs of chromosomes that make up the human genetic blueprint. That segment contains between 70 and 200 genes, a very small fraction of the 100,000 required to build a human being. The discovery of the actual gene involved with the disease, he added, could occur “next week or next year.”
