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| |  Scientists Discover New Link To Colon Cancer CLEVELAND, OH -- July 21, 1998 -- In a discovery that could lead to new ways to treat and even prevent colon cancer, a team of researchers at the Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University School of Medicine has identified a gene that, when it becomes defective and shuts off, causes colon cancer to develop in people who appear to have no family history of the disease. Even more significant, these researchers have demonstrated that the gene can be turned on again by a drug, making the colon cancer more vulnerable to be destroyed. The research was published in today’s issue of the Proceedings of the National Academy of Sciences. The study reaffirms the importance of a gene known as hMLH1, which had previously been linked to the development of hereditary non-polyposis colon cancer. "Now we know that when this gene is not working right, it leads to the more common form of colon cancer, the kind of cancer we see in people with no family history," said Sanford Markowitz, MD, principal investigator. "When the gene is working properly, it keeps cell DNA from being damaged. The gene produces an enzyme which detects a threatened breakdown of the DNA and, similar to a spell-checker in a computer, fixes the problem before the DNA is completely damaged." When the gene shuts down, the DNA becomes painted with a substance called methylation and the cell replicates abnormally. When a drug called 5-azacytidine is added to the gene, it works to strip the DNA of methylation and return the cell to a normal growth pattern. "We know the drug 5-azacytidine is toxic to people, so we need to develop a safer version of the drug. That's the next step in this research," Dr. Markowitz said. The discovery was made after analysing tissue samples from several colon cancer patients treated at Cleveland's Ireland Cancer Center. All the patients had presented with symptoms while in their 50s or 60s, the average age of onset for the most common kind of colon cancer. "We have proven that the hMLH1 gene is shut off in these patients' tumour tissue and we've shown how to turn it back on, to make it work the way it's supposed to," Dr. Markowitz explained. "We know that if we can turn this gene back on in people with colon tumours we can make their colon cancer more responsive to chemotherapy, more likely to be destroyed. "We also may be able to prevent the cancer from developing in the first place, if we can fix the gene as soon as it begins to shut down and protect the cell's DNA."
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