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. 2023 Sep 13:382:e076017.
doi: 10.1136/bmj-2023-076017.

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

Dag Holmberg  1 , Giola Santoni  1 , My von Euler-Chelpin  2 , Martti Färkkilä  3 , Joonas H Kauppila  1   4 , John Maret-Ouda  5   6 , Eivind Ness-Jensen  1   7   8 , Jesper Lagergren  9   10
Affiliations

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

Dag Holmberg et al. BMJ. .

Abstract

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.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted.

Figures

Fig 1
Fig 1
Standardised incidence ratios of oesophageal adenocarcinoma over follow-up time among patients with non-erosive (dashed line) and erosive (solid line) gastro-oesophageal reflux disease compared with the general population of the same age, sex, and calendar period
See this image and copyright information in PMC

Comment in

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Supplementary concepts