W hen David Kelsen embarked on a search in the late 1970s for potent chemotherapy drugs to        fight cancers of the esophagus, everyone in his research trial had squamous cell carcinoma, caused principally by smoking and alcohol abuse. Ten years later, Kelsen, chief of gastrointestinal oncology at Memorial Sloan-Kettering Cancer Center in New York City, was the lead investigator of a national trial designed to compare the effectiveness of surgery alone to chemotherapy followed by surgery. This time, though, many patients screened for the study had adenocarcinoma, an unusual cell type for a tumor at the junction of the esophagus and stomach. What’s more, most appeared to be otherwise quite healthy. “It was striking people who didn’t smoke, didn’t drink and exercised like crazy—very healthy guys in the prime of life,” says Kelsen.

The rapid proliferation of esophageal adenocarcinoma has continued, its rate of occurrence in the U.S. population growing faster than the rate for any other cancer. During the past 30 years, the number of new cases annually has skyrocketed more than 300%, and among white men, once only rarely diagnosed with the disease, the increase is almost 600%. “That kind of growth is unprecedented,” says Thomas Vaughan, head of epidemiology at the Fred Hutchinson Cancer Research Center in Seattle. Meanwhile, the once predominant type of esophagus cancer—squamous cell carcinoma—has been steadily dropping 3% to 4% each year as smoking and alcohol abuse also decline.

Even now, esophageal adenocarcinoma has hardly reached epidemic proportions. There were 14,520 new cases of esophagus cancer diagnosed in 2005 in the United States, 60% of which were esophageal adenocarcinoma. Those numbers pale in comparison to the incidence of other cancers among Americans that year—145,290 new cases of colorectal cancer, 172,570 of lung cancer and 211,240 of breast cancer. “But if you extend the growth curve of esophageal adenocarcinoma over the next 10 years, the numbers get pretty big,” Vaughan says.

Although white men have become the primary target of this disease (82% of all cases now involve Caucasian males), increasing numbers of black men and white women are also developing the tumor. “At the Cleveland Clinic, one in four of those with esophageal adenocarcinoma is a woman, and the disease is now affecting men younger than 50,” says Gary Falk, professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. And though the numbers remain small, this is a cancer you really don’t want to have. The average five-year survival rate is a grim 13%, and most patients die within a year of being diagnosed. But if the cancer is caught very early, the five-year survival rate jumps to 70%.

No one is sure why the rate of esophageal adenocarcinoma is spiking. Already, though, much is known about this relatively new disease. Its development tends to follow a linear progression: To get it, you will likely first have gastroesophageal reflux disease, or GERD, followed by a complication of GERD known as Barrett’s esophagus that may, in turn, lead to cancer. Having traced that path, scientists are hoping to put up roadblocks—stopping GERD from developing into Barrett’s esophagus, identifying those who have Barrett’s, determining whether they’re likely to get cancer and developing treatments. Yet each step of that seemingly straightforward approach has brought its own complications.

Barrett’s esophagus is characterized by elongated “goblet” cells resembling those in the intestines rather than the flat, smooth cells of the esophagus’s epithelium. “The normal lining is icy pink and looks like tile under the microscope,” says Yvonne Romero, a gastroenterologist at the Mayo Clinic Cancer Center in Rochester, Minn. “Barrett’s looks red to the naked eye and like shag carpet under the microscope.”

Being diagnosed with Barrett’s increases the risk of esophageal adenocarcinoma by as much as 125 times (though in a given year, only one in 200 people with Barrett’s esophagus will advance to full-blown adenocarcinoma). Part of the reason for the link, Romero suggests, is that as the damaged cells try to heal, they divide more frequently than normal and thus have a greater likelihood of mutating into cancer cells.

Once Barrett’s is diagnosed, patients can be watched closely, with biopsies of anything that looks suspicious, followed by aggressive treatment if cancer is found. But diagnosis is a major stumbling block. Of the 60 million Americans with GERD, only about 7% develop Barrett’s. And while those who have suffered years of chronic reflux are most at risk, 40% of people who develop esophageal adenocarcinoma have no symptoms at all. In Olmsted County, Minn.—one of only a handful of “enumerated” counties in which records are kept about every health care procedure for every citizen—just one in seven people with Barrett’s knew he or she had the disorder. “Using symptoms as an indicator of Barrett’s is not terribly helpful,” says Romero.