Researchers discover new genetic link to common colon cancer

Blood from families at risk contributed to discovery

A team of researchers from University Hospitals of Cleveland (UHC) and Case Western Reserve University have identified a specific location on a human chromosome that can be linked to familial cases of colon cancer–the type of colon cancer that tends to run in families.

Research published today in the Proceedings of the National Academy of Sciences (PNAS article #2286) identifies a specific stretch of DNA on chromosome 9 that houses a “susceptibility” gene. “Previous studies have shown that colon cancer risk can be inherited,” says Sanford Markowitz, MD, principal investigator for the study. “By analyzing blood samples from 53 families, in which at least one member of the family had a colon cancer or pre-cancerous colon polyp, we were able to find a common link. This moves us much closer to developing a blood test that will identify people who are susceptible to colon cancer well before the cancer ever develops.” Dr. Markowitz is a professor of cancer genetics at Case, a Howard Hughes Medical Institute investigator, and treats patients at University Hospitals Ireland Cancer Center.

Georgia Wiesner, MD, Director of the Center for Human Genetics at UHC and Case, and lead author of the study, notes that at least 200 genes exist on this particular location on chromosome 9. “Future research will focus on finding the one responsible gene,” says Dr. Wiesner. “The research team is looking for more sibling pairs and family members for the crucial next phase of the study, the actual identification of the disease-causing gene.”

In addition to Drs. Markowitz and Wiesner, the research team included Robert Elston, PhD, of the Department of Epidemiology and Biostatistics at Case, and Joseph Willis, MD, of the Department of Pathology at Case and UHC.

More than six years ago, Cleveland researchers began to recruit study participants who had at least one sibling affected with colorectal cancer or large colon polyps (adenomas, which are precursors to cancer) before the age of 65. Participants provided a sample of blood and underwent colon cancer screening. In some cases, study participants who had no symptoms of disease were discovered to have pre-cancerous polyps, and had them removed. Thus, participation in the study itself actually helped some high-risk patients avoid developing colon cancer.

Colon cancer is the second leading cause of cancer death among Americans. Studies have shown that nearly 30% of adults over age 50 have non-symptomatic polyps in the colon, precursors to cancer. Studies also show that brothers and sisters of individuals with colon polyps or cancer have triple the average risk for developing colon cancer themselves.

Previously, researchers at University Hospitals of Cleveland and Case discovered a genetic link to a rare form of colon cancer called Hereditary Nonpolyposis Colon Cancer (HNPCC) that tends to develop in young adults in certain families. The just-published study was designed to identify a genetic connection in more common colon cancers. The “Colon Cancer Sibling Study” combined the expertise of physicians and scientists from the departments of Genetics, Medicine (Oncology and Gastroenterology), Pathology, Epidemiology and Biostatistics at Case and UHC.

The current study received significant support from the National Cancer Institute, the National Colon Cancer Research Alliance (NCCRA) of the Entertainment Industry Foundation, and the Howard Hughes Medical Institute. Anyone interested in participating in the next phase of the “Sibling Study” should contact the Ireland Cancer Center Information Service at University Hospitals at 1-800-641-2422. The goal is to recruit 150 new families into the study to “ultimately provide identification of the putative disease gene that underlies this linkage.”

Media inquiries should be directed to Eileen Korey, Director of News Services at University Hospitals of Cleveland at 216-844-3825 or George Stamatis, Director of Public Affairs at Case School of Medicine at 216-368-3635.