SCIENCE COLORECTAL CANCER : New Genetic Technique for Early Detection Developed
Researchers have developed a new genetic technique that can detect more than half of all colorectal cancers before they become life-threatening.
Early detection of colorectal cancer is important because the disease has a 90% cure rate if the tumor is still localized in the intestine, but only a 10% cure rate when the tumor has eaten through the intestinal wall.
Tests for the disease, the third most common cancer, now rely on screening of stool samples for blood, but many tumors do not bleed and many benign conditions can produce bloody stools, confounding the diagnosis.
Researchers at Johns Hopkins University in Baltimore report today in the journal Science that they can detect in stool samples genetically mutated cells from the tumors with great accuracy, even while the tumors are very small.
Because the test is very expensive, the first use will probably be to monitor people with a genetic susceptibility to colorectal tumors and to watch for a recurrence in people who have had a tumor removed. But researchers are confident that costs will fall to permit wider screening, and they predict that the same technique can be used to screen for some other types of cancer, such as lung and bladder tumors, in which cells are shed into sputum and urine.
The new results are “very significant” because they mark the first time that genetic techniques have been used to detect cancer, said molecular biologist Sheila Taube, chief of cancer diagnosis at the National Cancer Institute. “I think it is very exciting to be making an attempt to really test this clinically.”
Cancers of the colon and rectum trail only lung and breast cancers in incidence. More than 570,000 new cases of colorectal cancer are expected worldwide in 1992, with 156,000 in the United States. More than 60,000 people will die of it in this country this year.
In current screening procedures, if blood is present in the stool, physicians then perform colonoscopy, in which a flexible tube containing a fiber-optic viewing device is inserted for a visual examination.
Although physicians are confident that screening for blood in the stool is useful, “there is no published data . . . showing a statistically valid decrease in mortality as a result of screening,” Taube said.
The new work was conducted by Hopkins molecular biologist Bert Vogelstein, one of the key researchers elucidating the genetic pathway by which colorectal tumors arise. He and other scientists have identified at least six genes that increase the risk of cancer when they become mutated or when a defective form is inherited.
He and his colleagues at John Hopkins and the M.D. Anderson Hospital in Houston focused on a particular gene, called the ras oncogene, because it is present in a mutated form in more than half of all colorectal tumors and because it mutates at an early stage of cancer initiation. They had already developed a probe that allows them to detect the mutated gene in DNA (deoxyribonucleic acid, the genetic blueprint of life) in cells.
They then obtained stool specimens from 24 patients scheduled to undergo surgery or colonoscopy for suspected colorectal cancer.
Nine patients had tumors containing the ras oncogene, and the researchers found cells containing the mutant gene in stools from eight of them. They also found the mutant cells in stools from two patients with early growths that had not yet become cancerous. In all cases, the patients were cured by removal of the tumors.
The findings are particularly encouraging, Vogelstein said, because no one was sure that such cells could be identified in stool--a complex mixture containing enzymes that can break down DNA and other biological materials. But, he said, they found the gene in much higher concentrations than they expected. Considerably more work is necessary before the tests can be widely used, Vogelstein said. It must be tested on a much larger number of patients to ensure its accuracy.
