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Delineating the pro-carcinogenic pathways activated in Barrett’s Oesophagus associated with obesity and excess adiposity.

Rory Casey, PhD Student
Rory Casey, PhD Student

Oesophageal adenocarcinoma is one of the most deadly human malignancies. Barrett's oesophagus is the only known clinical predicator of oesophageal adenocarcinoma, patients with Barrett's oesophagus are up to 120 times more likely to develop adenocarcinoma of the oesophagus compared to the general population.

Barrett's oesophagus develops in patients when the squamous cells native to the oesophagus are damaged by prolonged gastro-oesophageal reflux disease (GORD), more commonly known as heartburn.

Sometimes, when the cells damaged by GORD heal, they regenerate as columnar intestinal like cells, cells which are generally found lower in the digestive tract, this process is an example of metaplasia.

A major risk factor for the development of Barrett's oesophagus, is obesity. Central obesity (the build up of fatty on the abdomen) causes increased pressure on the stomach, forcing the bile and gastric acids from the stomach up into the oesophagus, subsequently damaging the squamous cells there. While GORD may have an important role in the pathogenesis of Barrett’s disease, the acid alone is not severe enough to account for Barrett’s oesophagus. GORD is relatively common in both sexes and across all ethnicities, but the risk of developing Barrett’s oesophagus and the subsequent progression to oesophageal adenocarcinoma is far greater in men of Caucasian ethnicity compared to any other group, indicating that other factors besides GORD are involved.

Central obesity may also be involved in the development of Barrett’s oesophagus and the progression of oesophageal adenocarcinoma by other mechanisms, and this is the main aspect of my research. Adipose tissue, not only serves as long term energy storage, but is also metabolically active. Adipose tissue is rich in agents that regulate a host of physiological processes related to carcinogenesis. Abdominal fat, is more metabolically active that subcutaneous fat and this observation may partially explain the increase rates of Barrett's oesophagus in men, as abdominal obesity is more common in men than women.

My research involves culturing Barrett's oesophagus cells in vitro, in media generated from visceral fat removed from oesophageal adenocarcinoma patients (to mimic the affect of obesity) and then identifying changes in the gene expression of the Barrett's cells, and relating these changes in gene expression to carcinogenesis. Identifying these genes in Barrett's cells, and then studying these genes in Barrett's oesophagus biopsies from patients, may help elucidate the molecular mechanism by which obesity promotes the progression of Barrett’s oesophagus to oesophageal adenocarcinoma and identify novel therapeutic targets that may limit the progression of Barrett’s oesophagus to Oesophageal Adenocarcinoma.

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Last updated 23 November 2016 Surgery - Web Administrator (Email).