Evolutionary Theory Predicts Progression of Barrett's Esophagus to Esophageal Adenocarcinoma

Evolutionary Theory Predicts Progression of Barrett's Esophagus to Esophageal Adenocarcinoma
Evolutionary Theory Predicts Progression of Barrett's Esophagus to Esophageal Adenocarcinoma

Applying evolutionary theory improves the accuracy of predicting in which patients Barrett's esophagus (BE) will progress to esophageal adenocarcinoma (AEC), a study published in Nature Communications has shown.1

Barrett's esophagus is damage to the esophageal lining caused by chronic stomach acid reflux. Although the condition can lead to esophageal adenocarcinoma, progression to cancer occurs in less than 5% of people with BE.

Because no known predictors are established to determine disease progression, all people with BE undergo routine endoscopic examinations and biopsy in an attempt to detect precancerous or cancerous lesions at an early stage. Therefore, researchers sought a potential biomarker that could accurately determine which factors indicate a risk of progression to cancer.

Chronic gastro-esophageal reflux transforms the tissue lining the esophagus into tissue resembling the lining of the intestine, resulting in the condition known as Barrett's esophagus. Researchers examined cell samples from the esophageal lining of 320 patients with BE who were cancer-free at the start of this study. Evaluations were conducted for 11 to 130 months. In this time, the condition progressed to cancer in 20 patients (6.3%).

In Barrett's esophagus, cells with mutations form clones. Selection preserves those clones most likely to help a tumor survive and expand over time. This process was not quantified prior to this study, despite its importance in the trajectory of cancerous tumors.

The researchers made an interesting finding regarding Barrett's esophagus: its genetic diversity does not increase over time. A co-existence of multiple clones was seen to come and go, maintaining a balance in genetic diversity, rather than a step-wise expansion of clones over time. Therefore, only BE lesions with a genetic diversity above a specified threshold develop into EAC.

Further analysis confirmed that genetic diversity of the condition does not change over time. Therefore, the risk of cancer for patients with Barrett's esophagus is predetermined by a baseline level of genetic diversity that remains constant. Highly diverse Barrett's esophagus lesions typically progress to cancer, whereas lesions with low genetic diversity do not.

This data has important implications for clinical surveillance and early treatment of Barret's esophagus, conclude the researchers, and further support using genetic diversity as a universal biomarker to assess risk of disease progression in cancer.

Reference

1. Martinez P, Timmer MR, Lau CT, et al. Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus. Nat Commun. 2016 Aug 19. doi: 10.1038/ncomms12158. [Epub ahead of print]

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