Barrett’s to Oesophageal Cancer Sequence: A Model of Inflammatory-Driven Upper Gastrointestinal Cancer

Abstract

Cancer-related inflammation is considered the ‘seventh hallmark of cancer’; many studies show that tumours develop and progress within inflammatory diseases. This review focuses on Barrett’s oesophagus, a common condition in which chronic inflammation and resulting alterations in the stroma can lead to carcinogenesis, specifically oesophageal adenocarcinoma. Changes that occur in the tissue microenvironment during development of this disease are discussed. Infiltration of immune cells facilitates tumour development through production of factors that promote carcinogenesis and by enabling tumours to evade the host immune response. Small molecules including cytokines, chemokines and growth factors play key roles in both inflammation and cancer by promoting proliferation, angiogenesis and carcinogenesis and by recruiting immune cells. The extracellular matrix is altered in inflammation, and provides structural support to developing tumours. Hypoxia is a common state in cancers and inflamed tissues which causes DNA damage and induces tumourigenic factors. Finally, tissue vasculature is a vital part of its microenvironment, supplying oxygen, nutrients and growth factors to rapidly dividing cells, and providing a mechanism for metastatic spread. The cells and molecules outlined here represent potential targets for treatment of this cancer, especially in its pre-cancerous, inflammatory stage.

Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett's oesophagus: a case-control study

“…Visceral abdominal obesity has been associated with increased risk of several disorders such as diabetes, ischaemic heart disease and malignancies including colorectal cancer 23 24. Visceral abdominal fat is metabolically active and has been associated with low serum levels of potentially protective adipokines (eg, adiponectin) and high pro-inflammatory cytokines (eg, interleukin-1β, interleukin-6 and tumour necrosis factor-α) 25. These cytokines may potentially increase the inflammation and hence the malignant transformation in patients with BE 26.…”

Glutathione Peroxidase 7 Suppresses Bile Salt-Induced Expression of Pro-Inflammatory Cytokines in Barrett's Carcinogenesis

“…The incidence rate for EAC has increased 4-10% per year among men since 1976, more rapidly than for any other type of cancer 1. The current paradigm suggests that EAC develops through chronic gastro-esophageal reflux disease (GERD), Barrett's esophagus (BE), dysplasia, and adenocarcinoma sequence 2-4. GERD is a condition whereby esophageal epithelium of the lower esophagus is abnormally exposed to a mixture of acid and bile salts 3, 5.…”

Ischemic heart disease, factor predisposing to Barrett’s adenocarcinoma: A case control study

“…Nevertheless, as those angiogenetic factors enter general circulation they can produce BE hyperproliferation and augment BE malignant potential [4] . After all, tissue hypoxia has been related to cancer development [31] and epidermal growth factor up-regulation due to cardiac ischemia [32] , can favor carcinogenesis within BE [33] . Finally, oxidative phosphorylation up-regulation [34] and subsequent reactive oxygen species overproduction, due to peripheral hypoperfusion increases the mutagenic pressure and raises genetic instability [35] .…”

“…The study included all BE or AdE cases, aged over 18 years living permanently either in Blackpool-Wyre-Fylde (BWF) NHS area (318886 inhabitants during 1991 census), between August 1, 1996 and July 31, 2001 or in the prefecture of Trikala (132689 inhabitants during 2001 census), between January 1, 2002 and December 31,2005. Study design was similar in both study periods [19] .…”