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It's not all genetic: Common epigenetic problem doubles cancer risk in mice

In experiments with mice, a team of scientists from the United States, Sweden and Japan has discovered that having a double dose of one protein is sufficient to change the normal balance of cells within the lining of the colon, thereby doubling the risk that a cancer-causing genetic mutation will trigger a tumor there. Roughly 10 percent of people have this double protein dose as well.

In the Feb. 24 online version of Science, the researchers report that mice engineered to have a double dose of insulin-like growth factor 2 (IGF2) develop more so-called precursor cells within the lining of the colon than normal mice. When these mice also carried a colon-cancer-causing genetic mutation, they developed twice as many tumors as those with normal IGF2 levels, the researchers report.

"Both clinically and scientifically, this discovery should expand attention in colon cancer research to earlier events, situations present well before tumors appear," says the study's leader, Andrew Feinberg, M.D., M.P.H., professor of medicine and director of the Center for Epigenetics in Common Human Disease at Johns Hopkins.

"In the mice with a double dose of IGF2, everything is pretty normal except for the extra precursor cells," says Christine Iacobuzio-Donahue, M.D., assistant professor of pathology and oncology. "But when the genetic mutation is present, too, we found a clear cost for what otherwise appears to be a benign effect of extra IGF2."

The team's analysis of colon tissue samples from a dozen or so Johns Hopkins patients with suspected colon cancer suggests that IGF2's effect in people may be similar, the researchers report. A larger study of samples from patients with and without suspected colon cancer is underway, Feinberg notes.

In the mice -- as well as in about 30 percent of colon cancer patients and 10 percent of the general population -- the extra IGF2 stems not from a genetic problem, or mutation, but an "epigenetic" prob
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
24-Feb-2005


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