Khaberni - A group of researchers at the University of Cambridge in the UK has clarified the precise relationship between Barrett's Esophagus and adenocarcinoma of the esophagus.
Barrett's Esophagus is a medical condition in which the lining of the lower esophagus changes so that it becomes similar to the tissues found in the intestines, as a result of chronic exposure to stomach acids, especially in patients with gastroesophageal reflux disease.
This change is not cancerous in itself, but it is important because it may be the first stage that precedes the onset of adenocarcinoma of the esophagus.
The disappearance of Barrett's cells in patients with this type of cancer at the time of diagnosis has puzzled scientists for nearly two decades, despite evidence confirming the association of these cells with the development of adenocarcinoma of the esophagus.
A recent observational study published in the journal Nature in April, led by Professor Rebecca Fitzgerald, has revealed indicators that support considering Barrett's Esophagus as a predictive marker for the onset of adenocarcinoma of the esophagus, making it a potential tool for early detection of this type of cancer.
Fitzgerald is a prominent British researcher and physician in the field of cancer prevention and early detection, holding the position of Professor of Cancer Prevention and Director of the Early Cancer Institute at the University of Cambridge. She is one of the scientific figures who has transformed esophageal and stomach cancer screenings through her pioneering diagnostic innovations.
The study, which included 3100 patients, was divided into two groups: the first included patients who clearly had Barrett's cells, and the second with no signs of them.
The researchers based their analysis on the clinical and epidemiological data of the participants, alongside conducting genome sequencing for samples from 710 patients, with the aim of exploring genetic aspects related to the disease's origin.
Revealing the pathway of the development of adenocarcinoma of the esophagus
The researchers assumed the existence of more than one pathway to understand the origin of cancer cells in the esophagus. They believe there are two main pathways that may provide an initial explanation for the development of adenocarcinoma of the esophagus.
The first pathway assumes that the disease may originate whether Barrett's Esophagus is present or not, indicating a difference in genetic factors and risk factors among patients.
The second pathway suggests the possibility of a single common starting point for the disease, which means similarity in genetic characteristics and risk factors among patients, thereby supporting the hypothesis that Barrett's Esophagus represents the primary path for the development of this type of cancer.
What did the results show?
No genetic differences between the cancer cells were found after their examination and the detection of their characteristics and genetic material inside them, which supports the second hypothesis that Barrett's Esophagus is the source of the onset of adenocarcinoma of the esophagus.
However, it is notable that only 35% of patients were confirmed to have Barrett's Esophagus, while the examinations of the rest were negative, showing no signs of Barrett's Esophagus especially in advanced cases of cancer.
In their quest to explain these findings, the researchers uncovered proteins called TFF3 and REG4 that were present in the esophageal cells of all patients even before cancer developed in them. This means - according to the researchers - that cancerous tissues consumed Barrett's cells and destroyed them during their growth, as the more these cells grew and spread, the more Barrett's cells dwindled and disappeared, which is why they were not found in advanced cases of adenocarcinoma of the esophagus.
Dr. Shahriar Zamani - one of the lead researchers in the study - asserts that adenocarcinoma of the esophagus follows a single path through Barrett's cells, meaning that one of the ways to prevent it begins with combating and treating Barrett's Esophagus.
Furthermore, the study led to a recommendation to rely on the TFF3 and REG4 proteins as one of the promising diagnostic biomarkers for predicting the likelihood of developing esophageal cancer.
Previous studies confirmed and supported
This study comes as a continuation of previous research that investigated the origin of esophageal cancer cells and tried to understand the mysterious relationship that links the increased risk of Barrett's Esophagus with adenocarcinoma of the esophagus specifically.
One of the most notable of these studies was published by the same researcher, Professor Fitzgerald, and her team in 2021 in the journal Science about the origin of adenocarcinoma of the esophagus cells, where the study revealed a series of changes that the cells in the upper stomach - called the gastric cardia - undergo to gradually transform into what is known as Barrett's cells that may start the cancerous proliferation causing adenocarcinoma of the esophagus.
The study at that time did not reveal the reasons for the disappearance of concrete evidence indicating Barrett's condition before esophageal cancer, but it confirmed that it might be an indicator that reveals the disease early, due to its role as an inevitable and primary mediator in the transformation of Barrett's Esophagus into adenocarcinoma of the esophagus.
The researchers relied on analyzing tissue samples from the lower part of the esophagus - between the stomach and the esophagus - in patients with adenocarcinoma of the esophagus, those with Barrett's Esophagus, and healthy individuals, then using advanced techniques for genetic analysis and detecting the origin of the cells.
The results showed an unexpected similarity between the stomach tissues and Barrett's cells, which - according to the researchers - means that all cancer cells of adenocarcinoma of the esophagus originate from gastric cells before undergoing genetic mutations led by the gene c-MYC and the gene HNF4A that drive them to radical transformations and assume the identity of intestinal cells despite their location above the stomach, on their way to form Barrett's tissues and cells.
What is Barrett's Esophagus and how common is it?
Barrett's Esophagus is a medical condition that affects about 0.8% of people around the world. In this condition, the lining of the lower esophagus changes, and pinkish-red mucosal tissues appear that extend at least one centimeter near the juncture of the esophagus with the stomach.
Although this condition is not cancerous, less than 5% of those affected may later develop adenocarcinoma of the esophagus, making it a significant medical concern.
The main reason: Chronic gastroesophageal reflux
Doctors believe that the most important cause of Barrett's Esophagus is chronic gastroesophageal reflux, which is behind about 15% to 20% of cases.
When esophageal cells are continuously exposed to stomach acids, permanent irritation occurs, leading to a change in the nature of these cells, so that they transform into cells similar to intestinal cells, performing functions close to them, known as goblet cells.
Can Barrett's Esophagus be avoided?
Despite the availability of various treatment options for Barrett's Esophagus, it is difficult to determine the most effective among them due to the absence of supporting evidence so far. However, the numerous scientific indicators that enhance the risk of Barrett's cells transforming into adenocarcinoma of the esophagus and confirm that it is the first step for this, necessitate understanding the causative factors of Barrett's Esophagus to try avoiding it and thereby reduce the risk of developing adenocarcinoma of the esophagus.
According to a massive Japanese study that included more than 600,000 people conducted by a group of researchers and published their results in the journal Nature in February 2026, a set of factors confirmed their association with Barrett's Esophagus independently of other influences:
Gastroesophageal reflux.
Esophageal diaphragmatic hernia.
Peripheral vascular disease.
Liver disease.
Helicobacter pylori infection.
Long-term use of acid-suppressing medications.
The incidence rate also increased among men and people aged between 50 and 79 years, indicating that age advancement plays a role, and while some factors such as age and gender cannot be avoided, others can be, encouraging regular screenings to detect some issues that may not accompany clear symptoms.
It should be noted that the study provided an impression of one Asian country - represented by Japan - and the association of certain factors with Barrett's Esophagus, but the dominance of a particular type of Barrett's Esophagus (Short-segment BE) among the Japanese population, along with the lack of histological data that allows distinguishing between the short and long types of Barrett's Esophagus, makes it one of the weak points that could limit the generalization of the results of this study.
