Case Western Reserve wins NCI grant to study genetic determinants of esophageal cancer

Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center are proud to announce the receipt of a highly competitive $5.4 million grant to study genetic determinants of Barrett's esophagus and esophageal adenocarcinoma. This five-year award from the National Cancer Institute will support the Barrett's Esophagus Translational Research Network (BETRNet), which consists of multiple centers collaborating to develop an understanding of the basis of Barrett's esophagus and its conversion to esophageal carcinoma. Researchers will also work to determine the role genetics and environmental factors play in the development and progression of these diseases, with the ultimate goal of reducing the mortality associated with this deadly cancer.

The BETRNet will be led by Amitabh Chak, MD, professor of medicine at the School of Medicine and a gastroenterologist at University Hospitals (UH) Case Medical Center, a leading figure nationally in translational clinical gastrointestinal cancer research.

"Dr. Chak has assembled a world-class group of investigators, bringing this group to the forefront of teams in the country to address an exceptionally important public health issue," says Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the Case Comprehensive Cancer Center, and director of the Seidman Cancer Center at UH Case Medical Center.

"The awarding of this grant by the NCI now is truly a recognition that the best cancer research is performed most effectively by a team of expert investigators," says Dr. Chak.

The BETRNet will be co-directed by other leaders in cancer research: co-principal investigators Sanford Markowitz, MD, PhD, Ingalls Professor of Cancer Genetics at Case Western Reserve and oncologist at the Seidman Cancer Center at UH Case Medical Center; Nathan A. Berger, MD, Hanna-Payne Professor of Experimental Medicine at Case Western Reserve and oncologist at the Seidman Cancer Center at UH Case Medical Center; and Robert Elston, PhD, Amasa B. Ford, MD Professor of Geriatric Medicine and chair of the Department of Epidemiology and Biostatistics; and consortium co-principal investigators Dr. William Grady, Professor of Medicine at the University of Washington and Fred Hutchinson Cancer Research Center and Dr. Nicholas Shaheen, Professor of Medicine at the University of North Carolina at Chapel Hill.

"The group of investigators assembled by Dr. Chak is world-class," says Dr. Grady. "I am honored to be a part of this group, and I am looking forward to the progress we will make in understanding and treating Barrett's esophagus."

Dr. Chak first developed an interest in esophageal cancer in the 1990s when he lost a patient to metastatic esophageal cancer, a fairly uncommon disease at its time. "I began to think that there has to be a genetic reason for why this cancer affected someone so young," remembers Dr. Chak. He credits early collaborative efforts with researchers in both in Cleveland and nationally for helping to expand research on Familial Barrett's esophagus to what it is today. The Familial Barrett's Esophagus Consortium (FBEC), developed by Dr. Chak, is now active in seven major institutions nationally, including Fred Hutchinson Cancer Research Center, University of North Carolina at Chapel Hill, Johns Hopkins University, Washington University in St. Louis, University of Pennsylvania, and the Mayo Clinic.

"Collaborations such as these between basic and translational scientists and clinical researchers will be essential to unravel the complex interplay between environmental and genetic influences on cancer development," says Dr. Shaheen.

Although the rate of many common cancers has declined in recent years, the rate of esophageal cancer has increased greater than six-fold over the past three decades. The prognosis for this cancer remains poor, accounting for more than one in 50 adult male cancer-related deaths. Though Barrett's esophagus, a precursor of esophageal cancer, can be easily recognized at endoscopy, current medical strategies of performing endoscopy based on the close association of Barrett's with chronic heartburn in adults are very inadequate. Nearly 40 percent of patients who develop esophageal cancer have no preceding symptoms of heartburn, and most people with heartburn never have endoscopy. Less than 5 percent of cancers are diagnosed at an early stage in patients whose Barrett's was recognized prior to cancer diagnosis.

The BETRNet will build upon Dr. Chak's work that has contributed to novel discoveries in the management of Barrett's esophagus and esophageal adenocarcinoma, such as defining the role of endoscopic ultrasound in the management of esophageal adenocarcinoma, developing unsedated transnasal endoscopy as a method for Barrett's screening, defining the clinical syndrome of familial Barrett's esophagus and demonstrating that it has a genetic basis, and recently discovering a role for insulin and insulin-like growth factors as mediators of obesity-associated cancers.

The BETRNet projects include discovery of genes that cause familial Barrett's esophagus, those which become targets of DNA methylation in Barrett's and in esophageal cancers, and those that are either turned on or turned off in Barrett's esophagus and in esophageal cancers. 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.