Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids

Abstract

Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori–negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids.

The relationship between gastric cancer, its precancerous lesions and bile reflux: A retrospective study

“…22 Another study on the etiology of cardiac cancer found that in environments in which production of acid is low, high concentrations of soluble bile acids may play the role of bactericides for H. pylori in the antrum. 23 However, a study on the inflammation of the remnant stomach after a gastrectomy found that bile reflux was not related to the severity of chronic and active inflammatory cellular infiltration or H. pylori infection. 24 Bile acid may affect the extent of gastric atrophy, regardless of H. pylori infection.…”

Alcohol drinking and gastric cancer risk: a meta-analysis of observational studies

“…Gastric cancer can be classified as cardia and noncardia subtypes according to the anatomic site. Some authors have investigated that the two subtypes are quite different in single-nucleotide polymorphism [ 41 ], causative factors [ 42 ] and risk factors [ 43 ]. In the present meta-analysis, we observed the positive association between alcohol drinking and the risk of gastric noncardia cancer instead of gastric cardia cancer, which strengthened their differences.…”

Fibroblast growth factor receptor 2 expression, but not its genetic amplification, is associated with tumor growth and worse survival in esophagogastric junction adenocarcinoma

“…First, GERD is more closely associated with EGJ adenocarcinoma than with distal gastric cancer. EGJ adenocarcinoma often arises from excessive gastric acid exposure through esophageal reflux, and is not associated with Helicobacter pylori infection [ 23 ]. Gastric cancer, however, arises in an atrophic gastritis setting, with reduced output of gastric acid.…”