Scientists announced on Apr. 16 that Barrett's esophagus is the starting point for all cases of esophageal adenocarcinoma, even when this pre-cancerous condition is no longer visible in patients. The findings were published in Nature Medicine and may help improve early detection and screening for this form of cancer.
Esophageal adenocarcinoma is the most common type of esophageal cancer in developed countries and ranks as the sixth deadliest cancer worldwide. The disease often goes undetected until it reaches an advanced stage, limiting treatment options.
Barrett's esophagus, which appears during endoscopy as a pink patch on the surface of the esophagus, affects about one out of every 100 to 200 people in the United Kingdom. While three to thirteen percent of those with Barrett's will develop cancer over their lifetime, around half of patients diagnosed with esophageal adenocarcinoma do not have detectable signs of Barrett's at diagnosis. This led researchers to question whether all cancers originated from this condition.
Professor Rebecca Fitzgerald from the Li Ka Shing Early Cancer Institute at the University of Cambridge said: "Cancer generally takes many years to evolve, giving us a window of opportunity to catch it before if develops into a life-threatening condition. Screening and preventative strategies can have a massive impact on the number of people who die from cancer, but if the link between precancers and cancer is unproven or unclear, screening programs risk doing more harm than good."
To investigate further, researchers analyzed clinical data from 3,100 patients across 25 UK centers who underwent surgery for their tumors or diseased tissue. They also examined whole genome sequencing data from 710 patients and whole exome sequencing samples from another group to understand tumor evolution.
The study found that DNA mutations and genomic patterns were essentially indistinguishable between cancers with or without visible Barrett's tissue during diagnosis. The main difference was that patients without signs tended to have more advanced tumors at discovery. Researchers identified proteins such as TFF3 and REG4 present throughout disease stages—including before cancer develops—suggesting these could be used as biomarkers for future risk assessment.
Dr Shahriar Zamani said: "We found no evidence for an alternative pathway to esophageal adenocarcinoma other than Barrett's esophagus. Because it seems to be the universal precursor, detecting Barrett's esophagus earlier could offer a clearer route to preventing esophageal cancer." Dr Lianlian Wu added: "What we need now are more sensitive, minimally invasive tests that identify people at risk based on molecular markers rather than relying solely on visible changes found during endoscopy."
The research received support from Cancer Research UK and other medical organizations including the Medical Research Council and National Institute for Health and Care Research Cambridge Biomedical Research Centre.
Professor Fitzgerald leads research efforts at Cambridge Cancer Research Hospital where early detection will be central; she has also developed a capsule sponge test aimed at diagnosing Barrett’s easily within primary care settings.
