BETHESDA -- Scientists at the Johns Hopkins Oncology Center have identified a genetic defect responsible for an inherited form of colon cancer and will soon test people to see if they are carriers.
The test, which should be available at Hopkins and selected research centers across the country within six months, could bring important news to people whose families have been wracked by the disease.
Carriers run almost certain odds of developing the disease. But those who know they inherited the gene could monitor their health for signs of a developing cancer in time to avoid fatal complications.
Meanwhile, non-carriers would be relieved of the anxiety of wondering if they are at risk.
"This is the essence of preventive medicine," said Dr. Francis Collins, director of the National Center for Human Genome Research, during a briefing yesterday at the National Institutes of Health.
Common genetic disease
The inherited form of colon cancer, called hereditary non-polyposis colorectal cancer, is thought to be the most common of all genetic diseases. Dr. Collins predicted that the test, once it is widely available, will become the most commonly used of all genetic screens.
The gene, carried by one in 200 people, also places women at a heightened risk of developing ovarian or uterine cancer.
Dr. Bert Vogelstein, one of two cancer specialists who directed the research, said that Johns Hopkins and an undetermined number of major centers across the country should be able to test at-risk families within six months as part of a continuing research project.
Initially, he said, it will be offered to people with at least one close relative who developed colon cancer before the age of 50 -- or with two close relatives regardless of age. It will cost about $1,000 for the first family member and half as much for subsequent family members.
Testing everyone who wants the test is certain to be a logistical feat, and researchers said yesterday it could be a few years before the test is widely available. An estimated 1 million people in the United States carry the gene -- about 1 in 200 people -- and as many as 5 million people have family histories that would qualify them for the test.
An estimated 152,000 Americans will be diagnosed with colon and rectal cancers this year, and 57,000 will die. About one-sixth of these cases are thought to be the inherited type.
Dr. Vogelstein said people who learn they are carriers would be advised to get annual colonoscopies, a test in which doctors examine the colon through a fiber-optic tube. Colon cancer is curable about 90 percent of the time when it is caught early.
Colonoscopies cost more than $1,000, but Dr. Vogelstein said people who learn they did not inherit the gene would not need them routinely. Currently, adults with family histories of the disease are all advised to get annual colonoscopies.
The discovery comes just six months after Dr. Vogelstein's team announced that it had located a region on chromosome 2 where the mutation was located, and would have a genetic test once it isolated the gene. (Every cell has 23 pairs of chromosomes.)
Locating the gene came much faster than expected, an accomplishment he attributed both to luck and the hard work of fellow scientists and research staff.
Scientists used sophisticated techniques of gene mapping to scan the human genome -- the full complement of genes carried by each human cell -- for the gene that was at fault.
The human genome consists of 3 billion units. With the most recent discovery, they isolated the defect to a culprit gene consisting of 3,000 units -- and to the single unit that triggers cancer.
"Research like this would have been science fiction 10 years ago," Dr. Vogelstein said.
The Hopkins team, led by Dr. Vogelstein and Dr. Kenneth W. Kinzler, collaborated with researchers at NIH and the University of Helsinki in Finland. In their search for the gene, they relied heavily on blood samples from large families in Newfoundland and New Zealand in which numerous people were afflicted.
The gene was independently found by a team led by Dr. Richard Kolodner of Boston's Dana-Farber Cancer Center and Dr. Richard Fishel of the University of Vermont.
The teams are reporting their findings this month in separate issues of the journal Cell.
Insights into cancer
The discovery also gives scientists a new way of understanding how cancer evolves. The normal gene functions like a computer spelling-checker, repairing genetic errors that commonly occur when cells divide.
In contrast, the mutant gene robs cells of their repair mechanism -- permitting other gene defects to go uncorrected.
The result is a rapidly developing cancer that can strike people in their 40s, 50s or 60s. Colon cancers that are not inherited typically strike people later in life.
People interested in being tested for the colon cancer gene can call the Johns Hopkins Oncology Center at 955-4041. A recorded message will ask them for information about their families' experience with the disease. Those deemed eligible for the test will be contacted later and scheduled for tests beginning in about six months.