Myo9B is associated with an increased risk of Barrett's esophagus and esophageal adenocarcinoma

Abstract

Background. Reflux esophagitis (RE) and Barrett's esophagus (BE) are predisposing factors for development of esophageal adenocarcinoma (EAC), the solid tumor with the fastest rising incidence in the Western world. This RE–BE–EAC cascade involves multiple host factors and consequently multiple genes. Polymorphisms in the 3′ region of myosin IXB (Myo9B) are associated with chronic inflammatory gastrointestinal disorders like celiac disease and ulcerative colitis, assuming that variation in Myo9B influences the intestinal permeability. Aim. To determine esophageal expression and the genetic variation of the Myo9B gene in the RE–BE–EAC cascade. Methods. DNA from 886 Caucasian participants (198 non-reflux controls, 305 RE, 254 BE, 129 EAC) was collected for the determination of the Myo9B gene polymorphism (rs2305764). Esophageal Myo9B expression was determined on biopsies from normal, RE, BE and EAC epithelium. Results. Genotype G/G was more common in BE (p = 0.032) and EAC (p = 0.046), but not in RE (p = 0.126) compared with the control group. Cytoplasmic Myo9B expression was determined in RE, BE and EAC, but most prominent in epithelial cells of BE and EAC. Conclusions. Genetic variation of Myo9B may play a role in the etiology of BE and EAC by increasing the permeability of the epithelial barrier.

Key Words::

• Barrett's esophagus
• esophageal adenocarcinoma
• Myo9B
• polymorphism
• reflux esophagitis

Acknowledgements

The authors would like to thank Jan Francke, Angela Heijens and Martine Ouwendijk for their technical assistance. They would also like to thank Dr. H. Geldof and Dr. W.A. Bode, and the nurses of the endoscopy units of the IJsselland Hospital and the Erasmus MC for their assistance in patient occlusion and collecting patient tissues and/or blood samples.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.