Anatomical Subsite–Specific Role of Helicobacter pylori in Gastric Adenocarcinoma

Abstract

Introduction: Gastric adenocarcinoma is still one of the major causes of cancer mortality worldwide. Anatomically, it is classified into cardia and non-cardia subtypes with distinct epidemiologic patterns and carcinogenic pathways. In this narrative review, we synthesized subsite-specific evidence from targeted searches of PubMed, Google Scholar, and ScienceDirect, supplemented by selected Persian-language sources, focusing on the role of Helicobacter pylori, gastritis phenotypes, acid- and gastrin-related changes, and eradication-related outcomes. Empirical evidence consistently supports a strong association between Helicobacter pylori infection and non-cardia gastric adenocarcinoma, whereas its relationship with cardia cancer is heterogeneous and appears to depend on the underlying epidemiologic context and coexisting risk factors such as obesity and gastroesophageal reflux disease. Available Iranian data suggest an “intermediate” pattern, with a persistently high burden of distal, infection-associated tumors alongside a substantial proportion of proximal tumors. An anatomical subsite–based framework may therefore help inform prevention planning in Iran; targeted detection and eradication in high-risk populations, together with attention to obesity- and reflux-related pathways in proximal tumors, may help reduce the overall burden of gastric cancer.