New research from scientists at UT Southwestern Medical Center and the Dallas Veterans Affairs Medical Center underscores the importance of preventing recurring acid reflux while also uncovering tantalizing clues on how typical acid reflux can turn potentially cancerous.
In research published in July and August, scientists discovered that people with acid reflux disease, particularly those with a complication of acid reflux called Barrett's esophagus, have altered cells in their esophagus containing shortened telomeres, the ending sequences in DNA strands. Combined with related research to be published this month, the findings indicate that the shortened sequences might allow other cells more prone to cancer to take over.
“The research supports why it is important to prevent reflux, because the more reflux you have and the longer you have it, the more it might predispose you to getting Barrett's esophagus. So you want to suppress that reflux,” said Dr. Rhonda Souza, associate professor of internal medicine at UT Southwestern and lead author of the paper which appears in the July issue of the American Journal of Physiology – Gastrointestinal and Liver Physiology.
Heartburn occurs when acid splashes back up from the stomach into the esophagus, the long feeding tube that connects the stomach and throat, causing a burning sensation.
Over time, the persistent acid bath can cause normal skin-like cells in the esophagus to change into tougher, more acid-resistant cells of the type found in the stomach and intestine, a condition called Barrett's esophagus, explained Dr. Stuart Spechler, professor of internal medicine and senior author of the paper. “Unfortunately, those acid-resistant cells are also more prone to cancer,” Dr. Spechler said.
Adenocarcinoma of the esophagus, the cancer that is especially associated with Barrett's esophagus, is currently the most rapidly rising cancer in the U.S., with a sixfold increase in cases during the past 30 years, according to the National Cancer Institute.
Understanding how and why the cells change in some cases and not others has been a major challenge for investigators.
Researchers compared telomere length and telomerase activity in biopsy specimens from 38 patients with GERD and 16 control patients. This new line of research suggests that the continuous acid bath affecting esophageal cells causes them to divide more frequently in order to regenerate the damaged lining. However, each time the cells divide, the telomeres at the end of DNA become shorter. When they become too short, the aging cell can no longer divide, Dr. Souza said.
Scientists suspect that when cells can no longer divide, other cells might infiltrate the area to make up for the loss. And those cells may be more likely to generate the acid-resistance that makes them more likely to turn cancerous.
“If the telomeres get short enough, maybe the cells can't regenerate any more and maybe that's why you start to see this change,” said Dr. Spechler. “Perhaps the esophagus can't regenerate the normal skin-like squamous cells, and instead, it has to recruit cells from somewhere else and that's why you start getting these changes to intestinal-like cells.”
Other studies by this group of UT Southwestern digestive disease specialists suggest the alternate cells that eventually take over might be bone-marrow cells.