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

BMJ 2023; 382 doi: (Published 13 September 2023) Cite this as: BMJ 2023;382:e076017

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Non-erosive reflux disease and oesophageal carcinoma

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Important to consider the effects of visceral obesity

Dear Editor,

The link between symptoms of gastro-oesophageal reflux (GORD), such as heartburn and regurgitation and risk of oesophageal adenocarcinoma (OAC) are well established, as are the putative pathophysiological mechanisms (1). This study is reassuring in that those with reflux symptoms but no endoscopic stigmata of reflux seem to have a risk equivalent to the population risk and although erosive disease is associated with a risk of OAC, the magnitude of the risk is relatively low and in isolation, is not a justification for surveillance.

It is important to stress that not all so-called erosive changes in the oesophagus are equivalent; whilst Los Angeles C-D grade are unequivocally diagnostic of GORD (2), and more recent ambulatory pH studies have confirmed that B-grade changes are also consistent with reflux (3), minor or grade A changes can be seen in the absence of pathological reflux.

Additionally, even classical or so-called typical symptoms of GORD are commonly not actually associated with pathological reflux (perhaps 30-50% of cases depending on context,) as both functional heartburn and reflux hypersensitivity are common (2). So pure symptom-based assessment is probably a poor determinant of cancer risk.

Obesity (especially visceral obesity) is the other important factor. Obesity amplifies the risk of OAC in conjunction with reflux as seen in both epidemiological and experimental studies and is probably a more important driver of risk than endoscopic stigmata of reflux (4,5). The current British Society Guidelines advocate case finding in those at highest risk of Barrett’s oesophagus (the main, if not only precursor lesion to OAC), with screening gastroscopy to those over age 50 and long history of GORD-symptoms combined with 2 additional risk factors, male sex, cigarette smoking or obesity (6).


1. Long E, Beales IL. The role of obesity in oesophageal cancer development. Therapeutic advances in gastroenterology 2014;7(6):247-68. doi: 10.1177/1756283x14538689 [published Online First: 2014/11/05]
2. Katzka DA, Pandolfino JE, Kahrilas PJ. Phenotypes of Gastroesophageal Reflux Disease: Where Rome, Lyon, and Montreal Meet. Clinical Gastroenterology and Hepatology 2020;18(4):767-76. doi: 10.1016/j.cgh.2019.07.015
3. Visaggi P, Del Corso G, Gyawali CP, et al. Ambulatory pH-Impedance Findings Confirm that Grade B Esophagitis Provides Objective Diagnosis of Gastroesophageal Reflux Disease. Official journal of the American College of Gastroenterology | ACG 9900
4. Alexandre L, Long E, Beales IL. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma. World journal of gastrointestinal pathophysiology 2014;5(4):534-49. doi: 10.4291/wjgp.v5.i4.534 [published Online First: 2014/11/18]
5. Beales IL, Ogunwobi OO. Leptin synergistically enhances the anti-apoptotic and growth-promoting effects of acid in OE33 oesophageal adenocarcinoma cells in culture. Molecular and cellular endocrinology 2007;274(1-2):60-8. doi: 10.1016/j.mce.2007.05.017 [published Online First: 2007/07/10]
6. Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut 2014;63(1):7-42. doi: 10.1136/gutjnl-2013-305372 [published Online First: 2013/10/30]

Competing interests: No competing interests

16 September 2023
Ian L. P. Beales
Clinical Associate Professor
Medical School, University of East Anglia