An estimated 20 million Americans have chronic heartburn. About 2 million of these people have Barrett's esophagus, a precancerous condition that affects the tube that carries food from the mouth to the stomach.
Barrett's-related esophageal cancer strikes about 10,000 Americans each year, and for unknown reasons the incidence of this cancer is rising faster than that of any other cancer in the U.S. More than 80 percent of patients with invasive esophageal adenocarcinoma die within five years of diagnosis.
While the condition is most prevalent in middle-aged white men, the incidence of Barrett's-related esophageal cancer is rising in women and African-Americans.
Fred Hutchinson Cancer Research Center is home to the Seattle Barrett's Esophagus Program, a multidisciplinary effort conducted in collaboration with researchers at Brigham & Women's College and the University of California at San Francisco. This research team has shown that a systematic approach to early cancer detection can boost five-year survival rates from about 15 percent to more than 80 percent.
Other promising findings from the Seattle Barrett's Esophagus Program suggest that modifiable lifestyle factors - from reducing obesity to quitting smoking - also may prevent progression of Barrett's.
Below are highlights of research findings, all of which were made possible by funding from the National Cancer Institute, which suggest ways to prevent the condition from progressing to esophageal cancer.
An aspirin a day may keep cancer away
A Fred Hutch study published in 2007 in PLOS Medicine found that people with the most aggressive form of Barrett's may benefit the most from preventive therapy with aspirin, ibuprofen and other nonsteroidal anti-inflammatory drugs, or NSAIDs. The same study, which followed about 250 Barrett's patients over 10 years, also identified a cluster of four known cancer biomarkers, or genetic abnormalities, in people with Barrett's that significantly increased their risk of developing esophageal cancer.
The researchers found that those with three or more of the cancer biomarkers upon enrollment in the study who also used aspirin or other NSAIDs had a 30 percent risk of developing esophageal cancer after 10 years, while those with the same biomarkers who did not use NSAIDs had a 79 percent risk of developing cancer within a decade of joining the study.
Ultimately the researchers hope that these biomarkers one day could be used in the clinic to identify which patients are most likely to develop esophageal cancer and therefore benefit from aggressive cancer surveillance via endoscopy and chemoprevention with aspirin and other NSAIDs. "Many Barrett's patients are subjected to overdiagnosis and overtreatment," said Brian Reid, M.D., Ph.D., director of the Seattle Barrett's Esophagus Program and member of the Human Biology Division at Fred Hutch. "These findings ultimately may help us identify high-risk patients who truly require frequent surveillance and low-risk patients who need no or less-frequent surveillance." The findings also may help determine which Barrett's patients may benefit most from a very cost-effective, noninvasive therapy in the form of aspirin or NSAIDs, Reid said.
It is hypothesized that aspirin and other NSAIDs may fight cancer by reducing chronic inflammation, which is a driving force behind the development of many cancers and other diseases. Specifically, NSAIDs have been shown to inhibit the production of the cyclooxygenase-2 (COX-2) enzyme. Disruption of this pathway slows the growth of abnormal cells and facilitates the normal process of programmed cell death, or apoptosis, both of which can thwart cancer development. NSAIDs are also believed to decrease the proliferation of cells and decrease the growth of blood vessels that supply blood to tumors.
Because this was a long-term observational study and not a clinical trial, the investigators cannot recommend NSAIDs for people with Barrett's and they advise anyone who considers taking these medications to do so under the direction of a physician, as they can cause side effects such as gastrointestinal bleeding.
Cholesterol-lowering drugs associated with reduced risk
Another Fred Hutch study published last year in Cancer Epidemiology, Biomarkers & Prevention that involved more than 400 patients with Barrett's found that overall, those who took statin drugs to lower their cholesterol had a 32 percent reduced risk of developing esophageal cancer. Among a subgroup of Barrett's patients with high-grade dysplasia, or cellular abnormality, those who took statins had a 59 percent reduced risk of esophageal cancer as compared to those who did not take such drugs. Those with high-grade dysplasia who took both statins and NSAIDs also had an 81 percent reduced risk of esophageal cancer as compared to patients who took neither.
Smoking and obesity - in particular belly fat - are other modifiable risk factors
Fred Hutch researchers earlier this year published a paper in PLOS One that looked at a variety of lifestyle factors - from smoking and obesity to alcohol use - to see whether they were associated with progression to esophageal cancer among a group of more than 400 patients with Barrett's.
They found that heavy smokers with Barrett's were more than twice as likely to develop esophageal cancer as non-smokers with Barrett's. The mechanisms underlying this relationship are unclear. In addition to the carcinogenic components of cigarette smoke and its potential effects on inflammation and cell proliferation, cigarette smoke also is thought to relax the esophageal sphincter, which could result in acid reflux, or chronic heartburn.
However, alcohol consumption did not appear to be a risk factor for esophageal adenocarcinoma among people with Barrett's. (Alcohol use is, however, associated with a 10-fold increase is risk of esophageal squamous cell carcinoma, the other major type of esophageal cancer.)
The researchers also found that abdominal obesity, or belly fat, was more strongly associated with progression from Barrett's to cancer as compared to a high body-mass index. While this finding needs to be confirmed, if there is indeed an association between abdominal fat and progression to cancer, it may be due to the inflammatory effects of fatty tissue and/or an increase in chronic acid reflux due to the intra-abdominal pressure exerted by extra belly fat.
SIDEBAR
Tips for managing the symptoms of chronic acid reflux, a risk factor for Barrett's
More than 20 million Americans experience chronic heartburn, or gastroesophageal-reflux disease. Of these, between 1 million and 2 million develop Barrett's esophagus, a premalignant condition of the esophagus.
"We know that most cases of Barrett's are caused by long-term, chronic acid reflux and that reflux probably influences progression of the condition toward esophageal cancer," said Thomas L. Vaughan, M.D., M.P.H., head of the Epidemiology Program and member of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center in Seattle.
Vaughan and colleagues offer the following suggestions to reduce the symptoms of acid reflux:
•Don't smoke.
•Keep your weight down.
•Get regular exercise.
•Eat a diet rich in fruits and vegetables.
•Refrain from eating four hours before bedtime.
•If you're having heartburn, sleep with the head of your bed elevated (talk to your doctor about how to do this).
•Avoid foods and beverages that promote heartburn, including alcohol, caffeine, chocolate, peppermint, onions, green peppers and foods that are high in fat, all of which can relax the muscle that prevents stomach acid from washing up into the esophagus.
•Take antacids as needed for occasional heartburn. Talk to your doctor if you have frequent heartburn or if over-the-counter medications don't relieve your symptoms.
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