Researchers link gene to onset of colon cancer


Researchers, led by a team based at the Johns Hopkins Oncology Center, have identified a gene they think may provide the earliest step in the lengthy development of colon cancer, the third-leading cancer killer of men and women.

If further research confirms that this "leading candidate" gene is involved in the hereditary form of colon cancer, people at high risk could learn through a blood test if they were carrying the damaged gene, said Dr. Bert Vogelstein, oncology professor at Hopkins, who headed the research effort.

Precautions, such as regular screening to remove growths -- called polyps -- from the colon, could be taken to prevent colon cancer or at least to catch the disease early enough to cure it.

"We are excited" about the finding, Dr. Vogelstein said yesterday. The candidate gene, named MCC for Mutated in Colon Cancer, is a mutated form of a gene thought to normally suppress tumor development.

Researchers are only now beginning to look for the mutated gene in patients with hereditary colon cancer. The Hopkins researchers have found the mutated gene in patients with very early colon tumors who do not have the hereditary form of colon cancer. That suggests this mutated gene may play a role in the more common colon cancer, which is not inherited.

"Such mutations are like smoking guns, strongly indicating that the gene is involved in the development of cancer," said Kenneth Kinzler, assistant professor of oncology at Hopkins and lead author of the study appearing in today's issue of Science magazine.

This is the fourth gene that the Hopkins group has identified in the development and spread of colon cancer, a process that may take 30 to 40 years. The other genes were the p53 gene, the DCC gene and the RAS oncogene.

Human cells have 23 pairs of chromosomes, which carry the genetic information that directs cell growth and function.

The newly discovered gene is located on chromosome 5, a site that was found in previous studies to sustain genetic damage in colon cancer.

Scientists will now check patients with inherited forms of colon cancer to see if they have this mutated gene, Dr. Vogelstein said.

The structure of this gene suggests it is involved in activating growth signals and may interact with a certain protein known to be important in regulating the growth of normal and cancer cells, the Hopkins researchers said. Eventually drugs may be developed that mimic the activity of this gene and could prevent people who inherited a damaged gene from getting colon cancer,the scientist said.

Colorectal cancer (cancer of the colon and rectum) is expected to kill 61,000 people in the United States this year, and an estimated 158,000 cases of colorectal cancer are expected to strike Americans this year.

Dr. Alfred G. Knudson, a leading cancer geneticist and senior nTC member of the Fox Chase Cancer Center in Philadelphia, called the latest Hopkins finding "very significant." The gene may be either mutated or missing in at least 50 percent of all colon cancer, Dr. Knudson said. Further

research may find that in the inherited form of colon cancer, the gene is severely damaged, while in the non-hereditary colon cancers, the gene is only slightly mutated, he suggested.

Dr. Vogelstein said it is likely that many colon cancer patients have inherited a gene such as the newly identified mutated gene that "predisposes them to cancer."

In addition to the Hopkins team, other researchers involved in discovery of the MCC gene included scientists from Japan, Britain and the University of Utah.

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