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Pathology and molecular pathogenesis of gastric cancer

Pelayo Correa, MD
Section Editor
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Gastric adenocarcinoma is one of the few malignant neoplasms for which infectious agents have been recognized as having an important etiologic role [1]:

In 1994, based mostly upon epidemiologic evidence, the International Agency for Research on Cancer (IARC), a part of the World Health Organization (WHO), recognized infection by Helicobacter pylori (H. pylori) as a primary cause of gastric adenocarcinoma [2]. Left untreated, H. pylori infection leads to life-long chronic active gastritis, which is a risk factor for both intestinal and diffuse gastric adenocarcinomas [3].

However, H. pylori-associated preneoplastic lesions are a feature of intestinal-type gastric cancer and not the diffuse-type. The diffuse type is more likely to have a primary genetic etiology, and the involvement of H. pylori is probably limited to a subset of sporadic cases [4].

Outcomes of H. pylori infection vary individually, and only a small minority of infected subjects develop gastric cancer (estimated at approximately three cases per year for every 10,000 infected persons). There are approximately 1,000,000 gastric cancer cases per year and 3.25 billion people infected with H. pylori worldwide. It is thought that modulation of the effects of H. pylori by genetic susceptibility, external (mostly environmental) forces, and possibly bacterial strain differences influence its evolution into a neoplastic or nonneoplastic process. (See "Association between Helicobacter pylori infection and gastrointestinal malignancy".)

Epstein–Barr virus (EBV) is detected in 2 to 16 percent of gastric adenocarcinomas worldwide; there is a higher frequency in tumors of the proximal and middle portion of the stomach [5-8]. Several EBV-related genes (including EBER-1, EBER2, EBNA1, LMP2A, BARF0, and BARF1) are expressed in gastric cancers. However, in contrast to H. pylori, their role in gastric carcinogenesis is not yet established.

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Literature review current through: Oct 2017. | This topic last updated: Nov 03, 2014.
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