Network Looks at Genetics of Esophageal Cancer

Recognizing the need to stimulate translational research in Barrett’s esophagus and esophageal cancer, the National Cancer Institute is funding a $5.4 million, 5-year grant to support projects through a consortia of institutions. Called the Barrett’s Esophagus Translational Research Network (BETRNet), it will involve projects spanning a number of institutions in the consortia to try to understand the causes of this cancer and develop better ways of preventing, detecting and treating it.

Nicholas Shaheen, M.D., M.P.H., professor in the UNC School of Medicine, adjunct professor in the UNC Gillings School of Global Public Health, director of the UNC Center for Esophageal Diseases and Swallowing and a member of UNC Lineberger Comprehensive Cancer Center, is one of the five co-principal investigators of BETRNet projects.

UNC’s Center for Esophageal Diseases and Swallowing is one of the few dedicated programs for esophageal disease in the U.S. It houses multiple physicians, basic scientists and researchers with a focus on finding the causes and treatments for esophageal diseases. UNC also has one of the largest groups of Barrett’s Esophagus patients under care in the country.

Barrett’s esophagus is a pre-cancerous condition caused by chronic acid reflux disease that can lead to esophageal cancer. Since 1975, the incidence of esophageal cancer has increased by 500 percent and what used to be a rare cancer is now the cause of death in more than 1 out of 50 adult male cancer deaths. Yet methods of prevention and early detection remain elusive.

“The cancer is highly lethal and spreads very quickly. So, if you wait until clinical presentation, the likelihood of cure is very small. That’s what makes me and others in this field very hot to understand prevention and early detection,” said Shaheen.

The reason for the rise in incidence is unclear, but obesity is one of the known risk factors. And, as Americans have become more obese, the incidence of both chronic acid reflux and esophageal cancer has risen as well.

“When you are fat, you have different cytokines circulating in your body. You have more insulin and more insulin-like growth factors. So we think that being overweight puts you at risk for multiple cancers, not just cancer induced by reflux, because you have a totally different biology,” said Shaheen.

The overall aims of the network are to develop new methods of identifying individuals at risk for Barrett's esophagus, early detection of Barrett's and esophageal cancers, and monitoring Barrett's esophagus to recognize when it is likely to progress to cancer.

Shaheen’s group proposed a series of projects to understand the genetics behind the cancer and also try to understand the heritability of this cancer. Earlier work suggests that at least some of the risk for this cancer runs in families.

The other co-principal investigators of the BETRNet consortium are Dr. Amitabh Chak, professor of medicine at the Case Western Reserve University (CWRU) School of Medicine; Dr. Sanford Markowitz, Ingalls Professor of Cancer Genetics at the CWRU School of Medicine; Dr. Nathan A. Berger, Hanna-Payne Professor of Experimental Medicine at CWRU; Dr. Robert Elston, Professor of Epidemiology and Biostatistics at CWRU; and Dr. William Grady, Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center. Roy C. Orlando, M.D., Mary Kay & Eugene Bozymski and Linda & William Heizer distinguished professor of gastroenterology and adjunct professor of cell and molecular physiology at UNC, is also a member of the BETRNet faculty.