University of Oulu

Holmberg, D., Santoni, G., Von Euler-Chelpin, M., Färkkilä, M., Kauppila, J. H., Maret-Ouda, J., Ness-Jensen, E., & Lagergren, J. (2023). Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries: Population based cohort study.BMJ 2023; 382: e076017.

Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma in three Nordic countries : population based cohort study

Saved in:
Author: Holmberg, Dag1; Santoni, Giola1; von Euler-Chelpin, My2;
Organizations: 1Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
2Department of Public Health, University of Copenhagen, Copenhagen, Denmark
3Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
4Department of Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland
5Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
6Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
7Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim/Levanger, Norway
8Medical Department, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
9School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link:
Language: English
Published: BMJ, 2023
Publish Date: 2023-10-24


Objective: To assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.

Design: Population based cohort study.

Setting: All patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019.

Participants: 486 556 adults (>18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease.

Exposures: Non-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy.

Main outcome measures: The incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period.

Results: Among 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15–31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up.

Conclusions: Patients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.

see all

Series: BMJ
ISSN: 0959-8146
ISSN-E: 1756-1833
ISSN-L: 0959-8146
Volume: 382
Issue: 8398
Article number: e076017
DOI: 10.1136/bmj-2023-076017
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: Swedish Research Council (2019-00209), Swedish Cancer Society (180684), and Nordic Cancer Union (186058). The funding sources had no role in the study design, analysis, interpretation of results, or writing of the manuscript.
Copyright information: © The Author(s) 2023. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: