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Medicineworld.org: How Acid Reflux Leads To Esophageal Cancer

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How Acid Reflux Leads To Esophageal Cancer

How Acid Reflux Leads To Esophageal Cancer
A particular enzyme is significantly higher in cancer cells that have been exposed to acid, leading to the overproduction of hydrogen peroxide, and offering a possible explanation for how acid reflux may lead to cancer of the esophagus, as per a recent study in the Journal of Biological Chemistry.

The study observed that the enzyme NOX5-S is affected by exposure to acid and that it produces stress on cells, activating genes that lead to DNA damage. For the first time, scientists have outlined the signaling pathway from cells damaged by acid, to the progression of esophageal cancer. They believe the same process may happen in the body when cells are exposed to acid reflux.

"The role of acid is controversial. But we show that by exposing cells to acid for short periods of time, that affects a particular enzyme, triggering a chain of events that possibly leads to cancer of the esophagus. Now that we have a better understanding of the signaling pathway, we can possibly identify who is at risk of developing cancer by determining the levels of this enzyme," says senior author Weibiao Cao, a researcher at Rhode Island Hospital and an assistant professor of medicine and surgery at Brown Medical School.

The study looked at human cancer cells and biopsies from patients with Barrett's esophagus (BE), a condition where cells in the esophagus have been altered by gastroesophageal reflux disease (GERD), or acid reflux. Acid reflux is thought to bea major risk factor for cancer in people with Barrett's esophagus.

However, the mechanisms of the progression to cancer have not been fully understood. In this study, scientists observed that the enzyme NOX5-S is significantly higher in Barrett's esophageal tissues, which creates a pre-malignant condition, as well as in esophageal cancer. Acid exposure leads to an increase in calcium in Barrett's esophageal cancer cells, thus activating a cAMP response element binding protein (CREB). This causes the activation of NOX5-S and overproduction of reactive oxygen species (ROS), thereby increasing cell growth and decreasing cell death - optimal conditions for cancer to develop.

It was previously known that levels of ROS are increased in Barrett's Esophagus and in esophageal cancer and that ROS may play an important role in the development of cancer. However, the sources of ROS had not been defined. Scientists showed that the production of ROS begins with NOX5. When this enzyme was removed, acid-induced production of hydrogen peroxide was reduced, confirming that NOX5 is responsible. Also, when calcium was removed, the prevalence of NOX5 decreased, along with the production of hydrogen peroxide.

"Now that we know the sequence, we may be able to slow down or even block the progression of cancer by blocking these different steps," Cao says. "This may have therapeutic value if we can block this particular enzyme, NOX5, in Barrett's esophageal cancer cells."

Incidences of esophageal cancer correlation to BE have increased over the past three decades at a rate exceeding that of any other cancer in the past 10 years. Patients have a poor prognosis, with a median survival of less than 18 months after diagnosis. The five-year survival rate is less than 20 percent after surgery on operable tumors. The major risk factor is gastroesophageal reflux disease (GERD) complicated by Barrett's esophagus.

Approximately 10 percent of GERD patients develop Barrett's esophagus. A middle-aged person with BE for 20 years or more has a 10 to 20 percent lifetime risk of developing esophageal cancer, which is similar to the risk of lung cancer among heavy smokers or of liver cancer among chronic hepatitis-B virus carriers.

In order to prevent the progression, it may be necessary to increase therapy with proton pump inhibitors in patients with Barrett's Esophagus, the authors write.

"Elucidating the pathways leading from acid exposure to increased ROS production, increased proliferation and decreased apoptosis may provide many potentially useful therapeutic targets," the authors write.



Posted by: Sue    Source




Did you know?
A particular enzyme is significantly higher in cancer cells that have been exposed to acid, leading to the overproduction of hydrogen peroxide, and offering a possible explanation for how acid reflux may lead to cancer of the esophagus, as per a recent study in the Journal of Biological Chemistry.

Medicineworld.org: How Acid Reflux Leads To Esophageal Cancer

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