Researchers have pinpointed the genetic basis of why some people with a serious complication of acid reflux known as Barrett’s esophagus go on to develop esophageal cancer. They believe their discovery, along with a novel non-invasive test, means esophageal cancer could be detected much earlier, thereby improving the prognosis of what is currently a cancer with a poor survival rate.

Writing in the journal Nature Genetics, the large international team, including scientists from the University of Southampton in the UK, describe how they found mutations in two genes mark the progression from Barrett’s esophagus to esophageal cancer.

They also describe how a new non-invasive tool that uses a “sponge-on-a-string” is capable of retrieving cells from the esophagus that can then be tested for mutations in the two genes.

Such a test has the potential to completely change the game for diagnosing esophageal cancer much earlier than at present.

According to the American Cancer Society, esophageal cancer makes up about 1% of all cancers diagnosed in the US, where estimates suggest in 2014, about 18,170 people will discover they have the cancer, and about 15,450 will die of it.

Although survival rates for esophageal cancer have improved since the 1960s and 1970s, when only 5% of patients survived at least 5 years after diagnosis, today that figure is still only about 20%. Survival rates for people with early stage cancer are higher.

There are two types of esophageal cancer: adenocarcinoma and squamous cell carcinoma. People with Barrett’s esophagus – a condition that can develop from prolonged, untreated acid reflux or heartburn – have a higher risk of developing adenocarcinoma of the esophagus.

Unfortunately, Barrett’s esophagus often goes undiagnosed, making it difficult to spot people who are at higher risk of developing esophageal cancer.

In this new study, the team sequenced the DNA of patients with Barrett’s esophagus and patients with esophageal cancer, and mapped out their genetic similarities and differences.

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The team sequenced the DNA of patients with Barrett’s esophagus and patients with esophageal cancer, and mapped out their genetic similarities and differences.

They found mutations in the genes TP53 and SMAD4 offered a way of identifying patients in which Barrett’s esophagus is progressing into cancer.

Another feature of the study was the use of a “non-endoscopic” test to identify high-risk Barrett’s esophagus by retrieving cells from the affected part of the esophagus that could then be checked for presence of the mutated genes.

The “non-endoscopic” test is the cytosponge, or “sponge-on-a-string” test, and involves the patient swallowing a capsule containing a sponge attached to a thread. When the capsule reaches the stomach it dissolves, releasing the sponge, which collects cells from the esophagus wall as it is pulled out by the clinician or nurse.

The cytosponge is still under development, but the researchers believe it could be used to look for mutations in TP53 and SMAD4 to identify patients with early stage esophageal cancer.

In collaboration with University Hospital Southampton NHS Foundation Trust, the University of Southampton provided the researchers with the second largest amount of samples.

Co-author Tim Underwood, a Medical Research Council (MRC) Clinician Scientist at the University, and esophageal surgeon at the Hospital, led the Southampton team. He says:

“This is a landmark study into the genetic basis of why and how some people with Barrett’s esophagus get esophageal cancer and others do not. It is still early, but we very much hope that this information will lead to a game-changer for a cancer with one of the worst outcomes.”

He says the findings also suggest “we may need to look outside the cancer itself to find the next generation of treatments.” He explains Southampton is already leading follow-on research that focuses on “disrupting the interaction between cancer cells and normal cells around the tumor that appear to support cancer growth.”

Co-author Rebecca Fitzgerald, a professor based at the MRC Cancer Unit at the University of Cambridge in the UK, says:

We developed the sponge-on-a-string test as an easy way of getting a sample of the cells that line the esophagus. When combined with powerful gene sequencing technology, this will help us to quickly identify which patients have Barrett’s and which have started to develop esophageal cancer, and we hope the test will soon be routinely available in hospitals.”

Nell Barrie, head of science information at Cancer Research UK, who were involved with funding for the study, says, “The Cytosponge test could be a simple and cheap way to help diagnose the disease earlier, when there’s a greater chance treatment will be effective.”

She also urges anyone who keeps having problems with food getting stuck when they swallow and persistent heartburn to see their doctor: “It probably won’t be cancer, but it’s essential to get checked out,” she says.

The study was funded by The Catalyst Club, which is organized by Cancer Research UK and is made up of philanthropists who have invested in a range of projects that aim to bring forward the day when all cancers are cured.

Meanwhile, Medical News Today recently reported how researchers discovered a promising biomarker for esophageal cancer. Presenting the results of their study at Digestive Disease Week in Chicago in May, the team said the new biomarker showed promise in improving screening for esophageal cancer and Barrett’s esophagus.