Barrett’s oesophagus identified as universal precursor to oesophageal cancer, study finds

A major new study has found the strongest evidence yet that Barrett’s oesophagus is the starting point for all cases of oesophageal adenocarcinoma, even when visible signs of the condition are absent at diagnosis.

Published in Nature Medicine, the findings could reshape how oesophageal cancer is detected and prevented. For patients, the study underscores the importance of identifying early, often hidden, precancerous changes, particularly as the disease is frequently diagnosed at an advanced stage when treatment options are limited.

Oesophageal cancer, including its most common form oesophageal adenocarcinoma, is rising in western countries and remains difficult to treat due to late detection. Barrett’s oesophagus has long been associated with the disease, typically identified during endoscopy as a visible abnormal patch in the oesophagus.

However, up to half of patients with oesophageal adenocarcinoma do not show detectable signs of Barrett’s oesophagus at diagnosis, raising uncertainty over whether it is always the precursor.

To address this, researchers led by Rebecca Fitzgerald at the University of Cambridge analysed epidemiological and clinical data from 3,100 patients undergoing surgery across 25 centres in the United Kingdom. They also examined genomic data, including whole genome sequencing from 710 patients and whole exome sequencing from multiple samples in 87 patients, to trace tumour development.

The analysis showed that cancers were genetically indistinguishable regardless of whether Barrett’s oesophagus was detected. DNA mutations, genomic patterns and cellular characteristics were consistent across cases, suggesting a single pathway of disease progression.

Although only 35 per cent of participants had a confirmed diagnosis of Barrett’s oesophagus, researchers identified molecular markers, including proteins TFF3 and REG4, in oesophageal cells across all stages of disease. This indicates that tumours may erase visible traces of the original precancerous tissue over time.

Patients without detectable Barrett’s oesophagus were more likely to present with advanced-stage tumours, reinforcing the challenge of late diagnosis.

Professor Fitzgerald said that cancer develops over many years, offering a window for early detection, but warned that screening programmes depend on clear links between precancerous stages and cancer to be effective and safe. Dr Shahriar Zamani, joint first author, said the study found no evidence of an alternative pathway to oesophageal adenocarcinoma beyond Barrett’s oesophagus, strengthening the case for earlier detection of the condition.

 Dr Dani Skirrow from Cancer Research UK said the findings highlight that early signs of cancer risk can be detected even when not visible, opening pathways for new diagnostic approaches.

The study provides a clearer framework for understanding how oesophageal cancer begins and points to a shift towards molecular screening. Detecting Barrett’s oesophagus earlier, even in its hidden forms, could play a critical role in preventing one of the most challenging cancers to treat.