No increase in cancer risk for most patients with reflux disease

Reflux disease manifests as acid regurgitation and heartburn and is a known risk factor for oesophageal cancer. However, a new study published in The BMJ by researchers at Karolinska Institutet now reports that the majority of patients do not have a higher risk of cancer. A large-scale study from three Nordic countries shows that the cancer risk is only elevated in patients whom gastroscopy reveals to have changes in the oesophageal mucosa.

­“This is a gratifying result since reflux disease is a very common condition and most patients are found to have a completely normal mucus membrane on gastroscopic examination,” says the study’s first author Dag Holmberg, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet and resident doctor of surgery at Karolinska University Hospital in Sweden.

In reflux disease, acidic stomach contents leak into the oesophagus. This can sometimes cause inflammation in the oesophageal mucus membrane (oesophagitis), which is diagnosed via gastroscopy. It is common knowledge that reflux disease increases the risk of oesophageal cancer, but what the cancer risk is for patients with normal mucosa has remained unknown.

The symptoms of reflux disease can come and go but generally persist, which means that many patients frequently seek medical attention and often undergo repeated gastroscopies to detect mucosal lesions or prodromal cancer.

“Our study suggests that these repeated gastroscopies are probably unnecessary for people with reflux disease who have a normal oesophageal mucosa,” says Dr Holmberg. “These findings should be reassuring for this large patient group and can guide GPs who often treat them.”

The present study is based on national health data registries in Sweden, Denmark and Finland, and included over 285,000 individuals with reflux disease and no gastroscopic evidence of oesophagitis. The patients were followed for up to 31 years and the researchers registered all cases of oesophageal cancer.

The cancer risk was then compared with that for individuals from the general population matched by age and sex and at the same period in the three countries. No increased risk of oesophageal cancer was observed in patients with reflux disease and a normal mucus membrane.

By way of comparison, the researchers also analysed the cancer risk in over 200,000 individuals with reflux disease and oesophagitis. These people were at a clearly increased relative risk of developing oesophageal cancer.

“We now intend to examine what factors other than oesophagitis can be linked to tumour growth in people with reflux disease,” says the study’s last author Jesper Lagergren, professor of surgery at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and consultant surgeon at Karolinska University Hospital.

The study was a collaboration between researchers at Karolinska Institutet and Karolinska University Hospital in Sweden, the University of Copenhagen in Denmark, and the universities of Helsinki and Oulu in Finland. It was financed by the Swedish Research Council, the Swedish Cancer Society and the Nordic Cancer Union. There are no reported conflicts of interest.

Publication: “Non-erosive gastro-oesophageal reflux disease and incidence of oesophageal adenocarcinoma: population-based cohort study in three Nordic countries”, Dag Holmberg, Giola Santoni, My Catarina von Euler-Chelpin, Martti Färkkilä, Joonas H Kauppila, John Maret-Ouda, Eivind Ness-Jensen, Jesper Lagergren. The BMJ, online 13 September 2023, doi: 10.1136/bmj-2023-076017.