New test for colon cancer Gene tracing could improve cure rates

Scientists in Baltimore have devised a test that searches stool samples for a genetic change associated with almost half of all colon and rectal cancers, offering hope for a more effective way to flag a developing cancer while it is small enough to cure.

It is the first test that detects cancer by looking for its genetic underpinnings, suggesting a new strategy for catching other cancers before they are too advanced to cure.


Although several years away from widespread use, the test represents a new turn in almost a decade of groundbreaking research into colorectal cancer by a scientific team at the Johns Hopkins Oncology Center.

"This is certainly the wave of the future," Dr. Sheila Taube, chief of the cancer diagnosis branch at the National Cancer Institute, said yesterday. "Exactly where each one of these efforts will land I can't say, but the techniques are so powerful that your feeling is that it can't help but somehow be useful in the long run."


The test, developed by Dr. Bert Vogelstein and colleagues at Johns Hopkins and the M. D. Anderson Hospital in Houston, looks for the cancer genes in a person's stool. It is based on the premise that if a person has a cancerous or pre-cancerous growth, some of the mutant genes will be shed into the stool.

Dr. Vogelstein said that other tests yet to be developed could search urine for genes associated with bladder cancer or sputum for the genetic signs of lung cancer.

The study is described in today's edition of the journal Science.

In the past decade, Dr. Vogelstein's team has found that most colorectal cancers are triggered by the accumulation of five separate mutations, a process that can take 30 to 40 years. The mutations cause normal cells to form small benign growths known as polyps that later develop into full-blown cancer.

Now, the team has unveiled a new test that detects one of those mutations, the "ras oncogene." It is a gene that appears in polyps or early cancers, so its detection could give a chance for a surgical cure before the cancer spreads to other tissues.

"This disease is only lethal in its most advanced stage, when it's spread to other organs," Dr. Vogelstein said. "The important thing from our viewpoint is that this provides the possibility for preventing lethal colon cancers."

Colon cancer can be cured about 90 percent of the time when it is still confined to the inner lining of the colon. Once it spreads to other organs, Dr. Vogelstein said, it is almost always fatal.

"The most important tumors to detect are those that have reached a certain size, about a third of an inch in diameter," Dr. Vogelstein said. "Ras gene mutations appear to occur just at that point."


Almost 160,000 people were diagnosed with colon and rectal cancers last year, and the diseases claimed an estimated 58,000 lives. Together, they are the second most lethal of all cancers, trailing only lung cancer.

Dr. Vogelstein cautioned that the ras oncogene mutation appears in only about 40 percent of all colorectal cancers, meaning that many people with developing cancers would test negative for it. Among other things, he said, the Hopkins lab will try to develop probes capable of finding the other mutations.

The ideal test, he said, would contain probes for all the mutations.

At least three years of research are needed before even the test for the ras oncogene can be declared an unqualified success, Dr. Vogelstein said. So far, the test was successfully applied to nine people with known colorectal cancers. In further research, the scientists will see how it works on hundreds of patients.

At present, a common screening tool for colorectal cancer is a test that looks for blood in a person's stool. The test is used because tumors often bleed, but most people who test positive do so because of other conditions.

People who test positive undergo a more definitive test called a colonoscopy, in which a fiber-optic tube is inserted through the rectum and into the colon and lower intestine. The physician uses this test to look for signs of tumors or polyps.


Similarly, the person who tests positive in a gene-based stool test would probably have a colonoscopy to give physicians a precise look at a tumor's size and location. But Dr. Vogelstein said the test might greatly reduce the number of people who undergo colonoscopies, which are both expensive and uncomfortable.

Colonoscopy costs about $1,000. Dr. Vogelstein said the genetic test would cost perhaps about $50.