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Acid Reflux and Esophageal Cancer

© David Olle

How could acid reflux lead to esophageal adenocarcinoma?

Acid reflux, commonly known as heartburn, occurs when the lower esophageal sphincter (a valve between the esophagus and the stomach) fails to close properly. This permits stomach contents such as acids, bile and food to enter the lower esophageal region, particularly after meals. Heartburn is characterized by a burning pain behind the breastbone. When the condition is long-standing, it can lead to inflammation and ulceration of the esophagus.

When acid reflux occurs over the long-term it can lead to a condition known as Barrett's esophagus. This condition changes the outer epithelial layer of the lower esophagus so that it assumes characteristics of intestinal cells. This may be a protective mechanism by the body against the effects of acid reflux. Barrett's esophagus is believed to be a forerunner to the development of esophageal cancer, since it involves cellular changes that are unnatural for esophageal tissue.

Under conditions of acid reflux, stomach acids and bile acids can result in proliferation of cells and can be carcinogenic. Inflammation can cause oxidative stress and the increased formation of free radicals. Free radicals, in turn, are notable in their ability to cause DNA damage, a hallmark of cancer genesis.

Studies that demonstrate the relationship

Lagergren and associates reported their findings on a comprehensive study that demonstrated that there was a strong association between the symptoms of gastrointestinal reflux and the risk of esophageal adenocarcinoma. The risk increased with increased frequency and duration of symptoms. The researchers found that Barrett's esophagus was a common, but not necessary step in the development of esophageal adenocarcinoma.

Prevention

Although it would seem that treatment of reflux disease would reduce the risk of esophageal cancer, there are no studies to demonstrate that this is the case. The Lagergren study, surprisingly, showed a higher risk in patients that received treatment.

The question whether patients at risk should submit to endoscopic screening is hotly debated. Lagergren estimated that if 1400 patients at high risk submitted to screening, only one case of cancer might be encountered. Obviously, a cost-benefit assessment needs to be done. Screening could be more cost-effective if researchers could find biomarkers that are less invasive and simpler. Microarray and proteomic technologies are promising in this regard.

Since cancers of the epithelium are characterized by an increased expression of cyclooxygenase 2(COX-2), drugs that inhibit COX-2 are showing promise in prevention of the diseases. Corley and associates recently reported on the results of a meta-analysis that indicated that aspirin and NSAIDs (non-steroidal anti-inflammatory drugs) had a protective effect. A meta-analysis is a compilation and statistical analysis of data from many studies to determine if there is an overall treatment benefit.

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