Major Advance in Search for Genes Associated with Colon Cancer

A 10-year study involving thousands of Israeli Jews and Arabs, led by researchers from American and Israeli institutions, has yielded important new information in the search for the genes that make a person more likely to develop colon cancer.

In a paper to be published in the July issue of Cancer Biology and Therapy, the international research team reports finding a significant link between genetic variation in a single region of human chromosome 8 and the risk of colorectal cancer.

The link was found by detailed comparisons of genetic material from thousands of colon cancer patients and non-patients, and by evaluating the incidence of colon cancer among the immediate family members of colon cancer patients.

In all, people who carry the specific genetic variation, called a marker, were found to be 23 percent more likely to have colon cancer than individuals without the marker. The researchers estimate that this single genetic variation might account for 14 percent of colorectal cancer cases in Israel, where colon cancer is the leading cause of cancer deaths. The specific marker is called the C allele of rs10505477.

Three other research teams are reporting similar findings today in the journal Nature Genetics, having simultaneously found their way to the same small area of chromosome 8, called 8q24, in the search for colon cancer genetic links. The fact that these studies were performed among other populations around the world suggests that this one genetic marker is highly influential across ethnic groups.

The new Cancer Biology and Therapy paper is by an international group of scientists from the University of Michigan Medical School and U-M School of Public Health, the Catalan Institute of Oncology in Spain, the CHS National Israeli Cancer Control Center and Technion - the Israel Institute of Technology.

It’s the product of an ongoing Michigan-Israel collaboration, the Molecular Epidemiology of Colorectal Cancer project, which for 10 years has searched for clues to colon cancer’s genetic roots using samples from large numbers of people in Israel with known ancestral heritage. The project is funded by the National Cancer Institute, with additional funding from the Irving Weinstein Foundation.

The researchers compared the genetic makeup and family history of more than 1,800 colorectal cancer patients with that of 1,900 healthy people with the same breakdown of age, gender and ethnicity - either Ashkenazi Jew, Sephardic Jew or Arab/non-Jew. Samples of tumor tissue from many cancer patients were also tested. The genetic link between the marker and colon cancer was especially strong among patients diagnosed with colon cancer at a young age, under 50 years.

Stephen Gruber, M.D., Ph.D., the co-leader of the Michigan-Israeli team and first author of the new paper, says that the new finding is particularly interesting when considered alongside recent discoveries in the genetics of prostate and breast cancer.