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Blood test for colon cancer risk to be goal of Hopkins project

e hasn't translated yet into a broadly applicable way to identify individuals most at risk," says Feinberg. "The BRCA1 and BRCA2 genes implicated in breast and ovarian cancers are great examples, but they are applicable only to a small percentage -- less than one percent -- of women."

But while the troublesome BRCA1 and BRCA2 genes stem from changes in the sequence of the DNA itself, the problems with IGF-2 are epigenetic -- changes in what is attached to the DNA.

The IGF-2 gene normally is controlled by an epigenetic process called "imprinting," in which the copy that used to make proteins depends on which parent the copy came from, rather than the Mendelian notion of dominant or recessive. For IGF-2, only the gene copy inherited from the father should be turned on, and that from the mother should be off. In about five percent to 10 percent of people, however, both copies of the gene are turned on -- a problem called loss of imprinting.

To check for loss of imprinting in people, the researchers will be looking for small methyl groups that should be attached to the DNA near the IGF-2 gene in blood cells from study participants. If neither gene copy has these methyl groups, both will be turned on, resulting in loss of imprinting.

The new project will build on the team's earlier work, funded by a planning grant from the Foundation, which shows that altered IGF-2 status can be detected in blood samples from Caucasians, African-Americans and Hispanics, and that the extra IGF-2 also seems to increase the number of primitive cells that allow the colon to regenerate its lining.

In addition to the practical science, the team will also evaluate the effectiveness of the informed consent process.

"All research investigators are required to obtain informed consent from human subjects. But there is a lot evidence that most consent forms are difficult to read and understand and that relying on the form alone is inadequate to inf
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
9-Sep-2005


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