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Discovery of genetic biomarker could improve diagnosis and treatment of cancer of the esophagus

November 13, 2000

Researchers at the University of Maryland School of Medicine and the University of Southern California have discovered a genetic biomarker that may help doctors to better diagnose and treat cancer of the esophagus, one of the most aggressive and deadly forms of cancer. The biomarker is an altered gene that can be detected and measured in the tumor itself and in the patient's bloodstream.

The research findings, published in the November 15th issue of the Journal of the National Cancer Institute, will help doctors more accurately determine the stage of the cancer, monitor the effectiveness of treatment, and check for a recurrence of disease.

"We hope our research will eventually lead to a dramatic increase in the survival rate for esophageal cancer," says Stephen J. Meltzer, M.D., professor of Medicine at the University of Maryland School of Medicine in Baltimore, and the study's senior investigator. "Although the treatment and understanding of this devastating disease is improving, more than 70 percent of patients die within three years of diagnosis."

Esophageal cancer is a malignant cell growth in the lining of the esophagus, the tube that connects the throat and the stomach. Risk factors for esophageal cancer include smoking, alcohol abuse, and long-term inflammation or irritation, such as chronic gastroesophageal reflux disease (GERD), a severe form of heartburn.

By analyzing tumor tissue DNA from patients diagnosed with two types of esophageal cancer, researchers found that the APC gene--normally responsible for suppressing cancer--had been deactivated. Within tumor tissues, the altered gene was found in 92 percent of patients diagnosed with esophageal adenocarcinoma, and in 50 percent of patients with squamous cell carcinoma of the esophagus.

The altered APC gene was also found in tissues from 40 percent of patients with Barrett's esophagus, a pre-cancerous condition caused by chronic severe reflux disease. In Barrett's esophagus, the normal lining of the esophagus is replaced by abnormal tissue. No altered genes were found in normal esophageal tissues.

"Gene alterations can occur randomly and as a result of exposure to carcinogens," says Peter V. Danenberg, Ph.D., professor of Biochemistry and Molecular Biology at the University of Southern California, and co-investigator. "But tumor cells lack the growth controls found in normal cells."

Dr. Meltzer and his colleagues have developed a blood test to detect the presence and the amount of altered APC genes in the bloodstream. "When high levels of the altered gene were found in the bloodstream, the survival rate was poor," says Dr. Meltzer, who is also director of the Aerodigestive Oncology Program at the University of Maryland Greenebaum Cancer Center."Conversely, the prognosis improves dramatically for patients with low or undetectable blood levels of the altered gene."

In newly diagnosed cases, this information may help doctors to more accurately determine the extent of the cancer, and decide on an appropriate course of treatment. For patients who have already been treated, the test could be used to detect a recurrence or to help reassure patients who are cancer-free. However, Dr. Meltzer cautioned that more research is needed to confirm the potential value of the blood test before it can be used in a clinical setting.

The American Cancer Society predicts that there will be more than 12,000 new cases of esophageal cancer diagnosed in the United States this year. About 12,000 people will die of the disease this year. Some countries such as Iran, northern China, India, and southern Africa, have rates that are 10 to 100 times higher than that of the United States.

"We hope our research will ultimately help improve the quality of life for those who suffer from esophageal cancer and eventually lead to better methods of early detection and treatment," says Dr. Meltzer. ###
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Contact: Larry Roberts(lroberts@som.umaryland.edu)
410-706-7590
Ellen Beth Levitt (eblevitt@umm.edu)
410-328-8919

University of Maryland Medical Center

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