WASHINGTON -- Scientists reported Thursday discovery of a gene suspected of playing a key role in colon cancer's earliest stages, a finding that may lead to better ways of detecting and treating America's No. 2 cancer killer.
A team of U.S., British and Japanese scientists reported that it has pinpointed a gene on the long arm of chromosome 5 that appears to be flawed in certain colon tumors.
All humans have 23 pairs of chromosomes which carry genes, the inherited blueprints for everything from hair color to the risk for developing certain diseases.
Three other genes already have been linked to colon cancer. But the newly discovered mutation, thought to remove a natural brake on cell growth, appears to occur earlier than the other defects in the pathway leading from normal cell growth to cancer's devastating, runaway growth, scientists said.
The team, headed by Dr. Bert Vogelstein of Johns Hopkins University School of Medicine in Baltimore, zeroed in on the so-called long arm of chromosome 5 after its previous work found people with an inherited tendency to colon cancer shared an unique genetic pattern in that area. The region was also known to be a frequent target of genetic damage in colon tumors in people without a strong family history of the disease.
Defective versions of the new gene, called mutated in colorectal cancer or MCC, were found in three of 100 colorectal tumors tested, researchers said. Although that level seems low, Kenneth Kinzler, co- author of the study, said the test was only capable of detecting a narrow range of mutations, and researchers suspect at least 40 percent to 50 percent of colon tumors have some sort of MCC defect.
Carl Barrett, of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., said MCC is 'a strong candidate' for a tumor suppressor gene, but 'much remains to be done to show it does indeed function in this way.'
'The real significance of this work is that Vogelstein has now been able to take a very common human cancer -- colon cancer -- and identify four different altered genes,' Barrett said.
'By having all the pieces of the puzzle at our disposal, we can begin to put together how these genes are interacting with each other .. . and try to understand how to turn on and turn off cancer.'
About 157,500 people are expected to develop colon cancer in the United States in 1991, and the cancer will likely claim about 60,500 lives -- second only to lung cancer, the American Cancer Society says.
In their study published in the journal Science, Vogelstein and his colleagues concede their results do not prove that MCC is the tumor suppressor gene thought to exist on chromsome 5.
To rule out the chance a different gene in the region may underlie cancerous growth, researchers are now conducting further tests.
Such research includes determining whether the gene is defective in all cells of people with a hereditary colon cancer susceptibility called familial adenomatous polyposis, or FAP. Preliminary results of such screening 'look promising,' Kinzler said.
If MCC does turn out to play a role in FAP, which is characterized by growth of polyps in the colon, Kinzler said the genetic information 'could be useful in predicting which patient may be at risk for developing colon cancer later in life.' FAP patients account for about 1 percent of all colon cancer cases, he said.
The genetic findings may also have implications for colon cancer treatment in general, Kinzler said.
'MCC may generate good targets for the development of new anti- cancer drugs,' said Kinzler, an assistant professor of oncology at Johns Hopkins.
The exact function of the gene is unknown, but its structure suggests it codes for production of a protein involved in carrying growth signals within the cell. Drugs designed to replace the action lost when MCC is defective might be able to block the early changes that open the door to colon tumor growth, he said.
Other institutions taking part in the research were the University of Utah in Salt Lake City, ICI Pharmaceuticals in Cheshire, England, and Japan's Cancer Institute in Tokyo.