What Is patientINFORM?

Researchers at Ohio State University Comprehensive Cancer Center and Northwestern University's Cancer Genetics Program have found a definitive link between an inherited genetic variation and colorectal cancer risk. The variation, which occurs on a gene known as TGFBR1, significantly increases a person's lifetime risk of getting the disease.

"This is a very exciting study," said Durado Brooks, MD, American Cancer Society Director of Prostate and Colorectal Cancer. "This represents a tremendous opportunity to intervene with intensive colorectal cancer screening and could also have near-term implications for developing new approaches to prevention and treatment."

The variation in question affects the receptor for TGF-beta, a protein that slows cell growth. The researchers found that this genetic variant makes the cell less sensitive to TGF-beta, so the cell doesn't get the signal to stop growth. If a person had colon cancer, those cells could proliferate more easily.

Researchers analyzed genetic samples and clinical data from 242 colorectal cancer patients (90 had a family history of the disease), and 195 cancer-free people who agreed to participate in the trial. All of the participants were white, and the average age fell in the mid-50s.

Ten percent to 20% of cancer patients showed a decreased production of a receptor for TGF-beta. Only 1% to 3% of healthy participants showed lowered numbers. The lifetime colon cancer risk of the patients with the genetic variation could be as much as 9 times that of those without the variation.

"This probably accounts for more colorectal cancers than all other gene mutations discovered thus far," said Boris Pasche, MD, one of the study's authors and Director of the Cancer Genetics Program at the Feinberg School and The Robert H. Lurie Comprehensive Cancer Center at Northwestern University.

While their findings still need to be tested in larger groups and in other racial and ethnic groups, the researchers hope to soon develop a clinical test that can be used to identify people who have the gene variant.

"We will be able to identify a large number of individuals that are at risk of colorectal cancer and in the long term, maybe decrease the cases of colorectal cancer and of people dying from it by being able to screen them more frequently," said Pasche.

While most colorectal cancer occurs in people who don't have a family member with the disease, up to 20% of people who get the disease have a family member who is affected. If you have a family history of colorectal cancer, you should talk to your doctor about colorectal screening before age 50, especially if you have a first-degree relative (parent, sibling, child) with the disease.

For more information about colorectal cancer and colorectal cancer screening, see Detailed Guide: Colon and Rectum Cancer and the American Cancer Society Guidelines for the Early Detection of Cancer.

Citation: "Germline Allele-Specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer." Published online in Science August 14, 2008. Corresponding author: Boris Pasche, MD, Northwestern University.