Scientists Pinpoint Genetic Changes That Predict Cancer
By GINA KOLATA
Published: May 16, 1989
RESEARCHERS are well on their way to determining the precise genetic changes that must occur to make a normal cell cancerous, an achievement that could make it possible to identify people susceptible to particular kinds of tumors.
The latest findings, which have been reported or privately discussed in the last few months, could also lead to tests that would tell a cancer patient whether the disease is likely to spread or will remain confined to a specific site in the body.
Some experts say that within three to five years doctors will be able to test the genes in patients' cells and tell them, for example, whether they have already suffered one of the four to six genetic changes that lead to colon cancer, or two of the 10 to 15 genetic changes that lead to lung cancer. Such information could offer clues to early treatment and warn susceptible individuals to avoid increasing their risk. A smoker who realized he was already well on the way to lung cancer, for example, would have a powerful incentive to quit.
In patients who have already developed cancer, gene tests are expected to allow doctors to determine whether a tumor will remain confined to a local site, where it can be removed entirely by surgery and radiation, or whether genetic changes make it likely that the tumor has spread its seeds elsewhere in the body, making it necessary to administer highly toxic chemotherapy.
The new genetic research began with very rare tumors in children that are caused by fewer genetic alterations. It has now moved on to the commmon cancers, where the alterations are more difficult to decipher. Among the common cancers, the work has progressed fastest in studies of colon cancer and lung cancer, and to a lesser extent, breast cancer. Experts say similar approaches are expected to work against a wide variety of other cancers.
Excited about the new findings, Dr. Samuel Broder, director of the National Cancer Institute, has formed a committee to help bring the new gene research to clinical practice as quickly as possible.
''There is so much information and so much excitement in the field,'' Dr. Broder said. He added that the recent findings are ''one of the real astonishing success stories of the national cancer program over the past 18 years.'' Dr. Broder said he formed the committee because ''we want to eliminate any bureaucratic or organizational issues'' that could impede the clinical applications.
The imminent clinical applications ''are not a pipe dream,'' said Dr. John Minna, who heads the cancer institute committee. Dr. Minna is the chief of the National Cancer Institute-Navy Medical Oncology Branch and professor of medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md.
But some researchers urged caution in predicting when the results will be put to clinical use. ''I'm enthusiastic but my enthusiasm is tempered by many experiences where things don't turn out as rapidly as we might like,'' said Eric Stanbridge, a professor of microbiology and molecular genetics at the University of California at Irvine who studies cancer genes in human cancer cells.
Cancer experts say they also are very aware of the ethical issues in cancer risk assessments. ''The obvious question is: should we really be genetically typing people?'' Dr. Minna said. People who learn they are highly susceptible to a particular type of cancer might find it difficult to get health insurance, for example, or may not be hired or promoted. But Dr. Minna said he thinks the health implications are so overwhelming that society will have to use the new genetic information. Sporadic Damage to Genes
In recent months, Dr. Bert Vogelstein of Johns Hopkins University and researchers there and at the University of Utah Medical Center in Salt Lake City have found that colon cancer occurs only after four to six genes are altered. Dr. Minna and his colleagues have found that one type of lung cancer, called small cell lung cancer, appears to occur as the culmination of a sequence of about 10 to 15 genetic alterations in a cell. Small cell lung cancer now accounts for about 20 percent of all lung cancers, or 35,000 to 40,000 new cases a year, Dr. Broder said, and the percentage has inexplicably been growing in recent years.
Dr. Dennis Slamon of the University of California in Los Angeles said breast cancer is also likely to be caused by an accumulation of genetic alterations. He and his colleagues have found that the extent of genetic alterations in cells from breast cancers seems to predict whether the cancer will spread. Although breast cancer researchers have not found a specific sequence of genetic changes that occur as normal cells become malignant, ''we are heading that way,'' Dr. Slamon said.
Among all the common cancers, research on colon cancer is the farthest along. Dr. Vogelstein and his colleagues have identified the genetic events that occur as colon cells go from being normal to forming a benign polyp to becoming cancerous.
The alterations probably occur as a result of sporadic damage to the genes in a single cell caused by carcinogens in food or water, for example. Each alteration of a single gene is harmless, but multiple genetic changes make a cell cancerous.