Germline NF1 Mutation Carriers, Neurofibromatosis Type 1 Patients May Be Predisposed to the Development of Barrettʼs Esophagus

Abstract

Purpose: One of the common genomic alterations of Barrett's esophagus (BE) is somatic loss of the q11 region of chromosome 17. This region of chromosome 17 is known to contain the tumor suppression gene NF1. Germline NF1 mutations are the cause of neurofibromatosis type 1 (NF type 1). Our aims were (1) to determine the prevalence of BE in patients with NF type 1 and (2) compare it to the prevalence in patients with cancer syndromes whose causative genes are not reported to be altered in initial development of BE. Methods: Patients with one of four cancer syndrome diagnoses were studied: NF type 1, Lynch syndrome, familial adenomatous polyposis, and hereditary breast ovarian cancer. Records were reviewed from Mayo Clinic Arizona, Florida and Rochester. Cancer syndrome patients who had had an upper endoscopy or documented history of BE were included in the data set. Results: BE was more common in the NF type 1 group than in other cancer syndrome groups. 30% of NF type 1 patients had BE (7 of 23), compared to 11% for Lynch syndrome (6 of 53, odds ratio [OR] 3.43; 95% CI 1.00-11.7), 6% for familial adenomatous polyposis (9 of 162, OR 7.44; 95% CI 2.44-22.7), and 0% for hereditary breast ovarian cancer syndrome (0 of 48). Five of 7 NF type 1 patients with BE were male. The mean age at diagnosis of BE was 52 years (range 19-71 years). Five patients had non-dysplastic BE, while one patient had low grade dysplasia and one high grade dysplasia. None of the seven patients had progression of their BE while under observation, however, only two patients had the results of more than one upper endoscopy recorded. Conclusion: BE was commonly found in NF type 1 patients who underwent endoscopy, compared with other cancer syndromes. The association is plausible as both BE and NF type 1 are associated with loss of NF1 function. Molecular studies and higher quality clinical studies are needed to confirm this association.Table: Table. Comparison of patients with eosinophilic infiltration with and without refluxTable: Table. Sensitivity, specificity, and predictive values of different maximum esophageal diameters