September 11, 2012

Enzyme counters stomach acid attack

Dysfunction or loss of an “antioxidant” enzyme may lead to higher risk for esophageal cancer in patients with gastric reflux disease.


Reflux of stomach acids into the esophagus promotes the buildup of reactive oxygen species (ROS), chemicals that can cause significant damage to cellular structures. ROS-induced damage to cells lining the esophagus can lead to a condition known as Barrett’s esophagus, a major risk factor for esophageal cancer.

Wael El-Rifai, M.D., Ph.D., the H. William Scott Jr. Chair in Surgery, and colleagues previously showed that GPX7, a member of the glutathione peroxidase family of antioxidant enzymes, is often silenced or lost in Barrett’s esophagus and esophageal cancer. However, the specific function of GPX7 was not clear.

In the September issue of Gut, the investigators report that GPX7 neutralizes ROS induced by bile acids and protects esophageal cells from oxidative damage. Loss of GPX7 led to the accumulation of high levels of ROS and oxidative DNA damage in esophageal cells.

The findings suggest that GPX7 protects esophageal cells from acid-induced oxidative damage – and that patients with GPX7 dysfunction could be at higher risk of developing Barrett’s esophagus and, subsequently, esophageal cancer.

The research was supported by grants from the National Cancer Institute (CA106176, CA138833, CA095103, CA068485) and the National Institute of Diabetes and Digestive and Kidney Diseases (DK058404) of the National Institutes of Health.