Mechanisms of Disease: Carcinogenesis in Barrett's Esophagus

Navtej S Buttar; Kenneth K Wang


Nat Clin Pract Gastroenterol Hepatol. 2004;1(2) 

In This Article

Helicobacter pylori Infection

The decreasing incidence of Helicobacter pylori infection concomitant with the increasing incidence of Barrett's-esophagus-associated esophageal adenocarcinoma prompted investigations into whether H. pylori infection may be protective against esophageal adenocarcinoma.[31] A prospective study[32] compared the prevalence of H. pylori infection among patients with Barrett's esophagus (n = 289) with and without concurrent dysplasia or adenocarcinoma and gastroesophageal reflux controls (n = 217). Of the patients with Barrett's esophagus, 47 had low-grade/indefinite dysplasia, 14 had high-grade dysplasia, and 20 had adenocarcinoma. Only 14% of patients with high-grade dysplasia and 15% of those with adenocarcinoma had H. pylori infection, compared with 44% of patients with GERD, 35% of patients with Barrett's esophagus alone and 36% of those with low-grade dysplasia. The study concluded that H. pylori infection might protect against the development of adenocarcinoma in Barrett's esophagus. There is further epidemiological evidence that patients who are H. pylori cell-surface antibody positive and are infected with the cagA+ strain have reduced risk of esophageal adenocarcinoma.[31,33] However, a recent study that controlled for demographic factors as well as lifestyle factors including BMI and smoking failed to establish a negative relationship between cagA+ H. pylori infection and esophageal adenocarcinoma.[34] Therefore, the epidemiological evidence regarding the protective role of H. pylori in esophageal adenocarcinoma remains controversial.

Changes in gastric reflux modulated by H. pylori colonization may account for its protective effect. Colonization with cagA+ strains of H. pylori produces severe inflammation of the gastric body, resulting in a less acidic gastric reflux, which may be protective against the development of esophageal adenocarcinoma.[33] Unfortunately, many of the studies that are attempting to address the negative association between gastric atrophy related to cagA+ H. pylori infection and esophageal adenocarcinoma fail to control for a common factor like excessive bile reflux, which may decrease the cagA+ H. pylori colonization and may also promote esophageal adenocarcinoma. Furthermore, a well-controlled study that found a negative association between cagA+ H. pylori and esophageal adenocarcinoma showed no association between gastric atrophy and esophageal adenocarcinoma. Although in-vitro experiments have shown that cagA+ H. pylori can cause apoptosis in esophageal cancer cell lines,[35] this may not be clinically relevant because Barrett's esophageal biopsies rarely show H. pylori colonization. The cancer-protective role of H. pylori in Barrett's esophagus therefore remains debatable.


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