Precision prevention of oesophageal adenocarcinoma

Abstract

Summary A rapid and continuous rise in incidence of esophageal adenocarcinoma over the past four decades has been well documented in many developed countries across three continents. Among white males, who are in the highest risk demographic, incidence has risen 10-fold in the U.S. since the early 1970s. Incidence among males in the U.K. are among the highest in the world, and 50% higher than in the U.S. Unfortunately, treatments have not kept pace; unless their cancer is identified at a very early stage, most individuals will not survive a year after diagnosis. The beginnings of this widespread problem were first recognized over 25 years ago, yet rates have continued to rise against a backdrop of much improved understanding and management including the introduction of medical and surgical treatments aimed at reducing acid reflux, one of the most important risk factors; the availability of screening and surveillance programs for the precursor lesion Barrett’s metaplasia; and the development of endoscopic therapies for prevention or treatment of early invasive cancer. We estimate that only about 7% of the 10,000 cases of esophageal adenocarcinoma diagnosed annually in the U.S. are identified through current approaches to cancer control, and trace pathways by which the remaining 93% are “lost.” Based on emerging data on etiology and predictive factors coupled with new diagnostic tools, we suggest a five-tier strategy for prevention and control that begins with a wide population base and triages individuals into progressively higher risk strata, each with risk-appropriate prevention, screening and treatment options.

Risk stratification of Barrett's oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study

“…1 The burden of OAC could be reduced by diagnosing more cases of the precursor lesion Barrett's oesophagus (BO) while identifying those at increased risk for cancer development before treating them endoscopically. 2 However, this is a formidable task since the incidence of gastro-oesophageal reflux is approximately 5 per 1000 person-years in the UK. 3 Furthermore, despite clinical guidelines for endoscopic referral, primary care practice varies and low endoscopy referral rates correlate with poor outcomes.…”

Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma

“…The incidence of esophageal adenocarcinoma (EA) has risen rapidly over recent decades in Western countries [1, 2]. EA typically arises within a metaplastic precursor epithelium known as Barrett’s esophagus (BE) [3].…”

Transitional basal cells at the squamous–columnar junction generate Barrett’s oesophagus

“…Barrett’s oesophagus is the precursor lesion of oesophageal adenocarcinoma which has registered an approximately 800% increase in incidence over the past four decades 9 . Histologically, BE is characterized by the replacement of the stratified squamous epithelium of the distal oesophagus with simple columnar epithelial cells which often express characteristics of intestinal differentiation (e.g.…”