To create this new test, researchers, like Dr. Grady, in the UW GI Division are identifying the earliest molecular changes that can accompany a normal intestinal cell’s transition into cancer. Some of these changes involve chemical modifications to the DNA, called DNA methylation, and others involve mutations of the DNA. These molecular changes are not only promising molecular markers for colon polyps and cancer, but they are also targets for new therapies for colon cancer. Importantly, theses investigators must also develop strategies to overcome the technical obstacles in detecting minute amounts of cancer-related DNA in a vast sea of normal DNA located in the blood or stool. In order to do that, they have teamed up with researchers across the country, as well as with many of the local biotechnology companies, as a way to springboard these assays into clinical care.

Researchers at UW Medicine and at the Fred Huchinson Cancer Research Center are also studying how these molecular changes cause a normal cell in the colon to change into colon cancer. For instance, Dr. Grady’s lab also investigates the consequences that result when genes become methylated. The answers could lead to the development of new drugs that block methylation or the tumor-promoting effects caused by methylation, thus preventing cancer from ever developing. Several members of Dr. Grady’s lab focus their research on a protien called TGF-beta receptor type 2, a protein often found to be abnormal in colorectal cancer patients that have methylated genes in their tumors. Scientists suspect that abnormalities in the TGF-beta receptor are one of the causes for colon polyps turning into colon cancer.

In addition to the exciting research on the molecular alterations of colon cancer, researchers in the UW GI Division are also actively studying how to improve the prevention and treatment of colon cancer through improving our understanding of the clinical nature of this disease.

In addition to the innovative research going on at UW Medicine and at the Fred Hutchinson Cancer Research Center, the Seattle Cancer Care Alliance has recently started the GI Cancer Prevention Program, a clinic for people, who by their family history, have an increased risk of developing gastrointestinal cancer. The clinic is a multi-disciplinary clinic for people known to be at high risk for colorectal, gastric and pancreatic cancer.

“An example of someone at high risk would be a person who has a family member who has been diganosed with one of these cancers at an early age,” says Dr. Grady, the Medical Director of the GI Cancer Prevention Program. “We will provide a risk assessment for that individual and their family members, including genetic testing and counseling for known hereditary cancer syndromes. Based on the results of the risk assessment, patients will receive individualized cancer surveillance recommendations and will be offered opportunities to participate in clinical trials aimed at cancer prevention and detection.”

Program health-care providers include gastroenterologists, geneticists, genetic counselors, gynecological oncologists, and nutritionists.

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