Study Finds Association Between Increased Esophageal COX-2 Expression and Barrett’s Esophagus, Obesity, and Smoking


Key Points

  • Overexpression of cyclooxygenase-2 (COX-2) has been reported in both Barrett’s esophagus and esophageal adenocarcinomas.
  • In a case-control study, a significantly higher median COX-2 expression level was reported in Barrett’s esophagus tissue than in squamous tissue.
  • Elevated COX-2 expression levels were found to be associated with high waist-to-hip ratios and current tobacco smoking.

Elevated esophageal mucosa cyclooxygenase-2 (COX-2) levels appear to be associated with the presence of Barrett’s esophagus as well as high waist-to-hip ratios and current tobacco smoking, according to the results of a study reported by Nguyen et al in Digestive Diseases & Sciences. These novel mechanistic connections may help clinicians to identify patients who may benefit from chemoprevention with COX-2 inhibitors.

The membrane-bound glycoprotein COX-2 has been implicated in the development of many gastrointestinal cancers, such as esophageal adenocarcinoma. Although overexpression of COX-2 has been reported in both Barrett’s esophagus and esophageal adenocarcinomas, little is known about the clinical or sociodemographic determinants that may influence the levels of COX-2 in subgroups of patients at high risk of developing such cancers.

Study Details

Nguyen and colleagues conducted a case-control study to explore the link between several clinical and sociodemographic factors and esophageal COX-2 expression in the development of Barrett’s esophagus. Recruited from the Michael E. DeBakey Veteran Affairs Medical Center in Houston, eligible study participants were scheduled for elective esophagogastroduodenoscopy. In addition, patients eligible for screening colonoscopy were recruited from seven primary care clinics at the Center.

Among the study inclusion criteria were age between 40 and 80 years (mean age, 61.2 years), no prior gastroesophageal cancer or surgery, and no history of major stroke. Approximately two-thirds of patients were white, and most (93%) were men.

Participants with definitive Barrett’s esophagus served as cases, from whom 39 Barrett’s esophagus tissue samples and 47 squamous tissue samples were obtained. Patients who did not have endoscopically suspected Barrett’s esophagus served as controls, and 240 squamous tissue samples were obtained from them. Furthermore, patients’ body weight and height were measured, and their waist-to-hip ratio was calculated. Immunohistochemical staining for the presence of esophageal COX-2 was performed.

Higher COX-2 Expression Levels in Heavier Patients, Current Smokers

The investigators reported a significantly higher median COX-2 expression level in Barrett’s esophagus tissue than in squamous tissue from cases or controls (P < .001). However, they found no difference in COX-2 expression between squamous tissue from cases and controls (P = .950).

In addition, they found a trend of higher median COX-2 expression levels in tissue samples from those with a waist-to-hip ratio in the second (0.93–0.98) and third tertiles (> 0.98) than in tissue samples from patients in the first tertile (< 0.93; P = .053). For patients in the second and third tertiles, the unadjusted odds ratio (OR) was 2.04 and 2.24, respectively, and the 95% confidence interval (CI) was 1.17–3.57 and 1.20–4.16, respectively.

Median COX-2 expression levels tended to be higher in current smokers than in never or former smokers (P = .075). However, the investigators noted that the levels of COX-2 expression did not appear to differ significantly with age, gender, race, Helicobacter pylori status, proton pump inhibitor use, and alcohol consumption.

Closing Thoughts

The investigators reported a possible connection between elevated levels of COX-2 expression and an increased risk of Barrett’s esophagus. A relationship between increased COX-2 expression and high waist-to-hip ratios and current tobacco smoking also was revealed in this study.

“In addition to a possible mechanistic association between abdominal obesity and Barrett’s esophagus, these results point toward potential subgroups who may be targeted for chemoprevention using [aspirin] or [nonsteroidal anti-inflammatory drugs] or who may benefit from antireflux surgery,” concluded the investigators.

Hashem B. El-Serag, MD, MPH, of the Department of Medicine, Baylor College of Medicine, Houston, Texas, is the corresponding author of this article in Digestive Diseases & Sciences.

This research was supported in part by the Veterans Affairs Health Services Research and Development Center for Innovations in Quality, Effectiveness, and Safety, at the Michael E. DeBakey Veterans Affairs Medical Center, in Houston. This work also was funded in part by the National Institutes of Health, the Houston Veterans Affairs Health Services Research and Development Center of Excellence, and the Texas Digestive Disease Center. The authors reported no potential conflict of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.