Gastrointestinal Oncology
Helicobacter pylori Infection and Gastric Adenocarcinoma Pelayo Correa, MD1
and Maria Blanca Piazuelo, MD2 1. Anne Potter Wilson Professor of Medicine; 2. Research Instructor, Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine
Abstract
Gastric adenocarcinoma is the second leading cause of cancer-related mortality worldwide. Infection with Helicobacter pylori is the strongest recognized risk factor for gastric adenocarcinoma. This bacterial species colonizes the stomach of more than half of the world’s population; however, only a very small proportion of infected subjects develop adenocarcinoma. H. pylori causes a chronic gastritis that may last decades, and a multistep precancerous process is recognized for the most frequent histologic type of gastric adenocarcinoma: the intestinal type. The severity and long-term outcome of this infection is modulated by an increasing list of bacterial, host, and environmental factors, which interplay in a complex manner. Identification of individuals at high risk for gastric cancer that may enter a surveillance program and intervention during the precancerous process is the most suitable strategy for decreasing mortality due to this malignancy.
Keywords Gastric cancer, gastric adenocarcinoma, Helicobacter pylori, CagA, VacA, multifocal atrophic gastritis, intestinal metaplasia, dysplasia
Disclosure: The authors have no conflicts of interest to declare. Acknowledgments: This work was supported by the grant P01-CA28842 from the National Cancer Institute. Received: March 9, 2011 Accepted: June 1, 2011 Citation: US Gastroenterology & Hepatology Review, 2011;7(1):59–64 Correspondence: Pelayo Correa, MD, Division of Gastroenterology, Vanderbilt University School of Medicine, 2215 Garland Avenue, 1030 MRB IV, Nashville, TN 37232. E:
pelayo.correa@
vanderbilt.edu
Although gastric cancer incidence and mortality rates have been slowly decreasing in many countries over the last five decades, gastric cancer is still the second most common cause of cancer-related deaths and the fourth most common malignancy worldwide (see Table 1).1 Approximately one million cases were estimated for 2008, 70% of them in less developed regions.1
Overall, gastric cancer has a poor prognosis. In the US, two-thirds of the cases are diagnosed when the tumor has reached some degree of dissemination through the gastric wall, and the overall five-year survival rate is 25%.2
For most of the 20th century the search for the causes of cancer emphasized the role of ionizing radiation and exposure to chemical carcinogens, especially tobacco smoke, which is a recognized risk factor for malignancy in multiple organs, including the stomach.3
The 21st
century has brought more attention to infectious agents and chronic active inflammation as primary causes of some cancers. Convincing evidence has become available for the oncogenic role of two virus families: papilloma viruses in carcinoma of the uterine cervix and hepatitis viruses in hepatocellular carcinoma. So far, only one bacterial species has been implicated: Helicobacter pylori in gastric carcinoma.4
It has been
estimated that 17.8% of cancers worldwide are due to infectious agents, and H. pylori is estimated to be responsible for 5.5% of all cancer cases and more than 60% of gastric cancer cases.5
Although H. pylori is also © TOUCH BRIEFINGS 2011
implicated as a causative agent in gastric mucosa-associated lymphoid tissue lymphoma, this article is focused on gastric adenocarcinomas, which account for more than 90% of gastric cancer cases. Other infectious agents classified as carcinogens by the International Agency for Research on Cancer (IARC) are: Epstein-Barr virus (EBV or HHV4) in lymphomas and nasopharyngeal carcinoma, herpes virus 8 (HHV8) in Kaposi’s sarcoma, human T-cell lymphotropic virus type I (HTLV-1) in adult T-cell leukemia-lymphoma, Schistosoma haematobium in bladder carcinoma, and Opistorchis viverrini in cholangiocarcinoma.6
Additionally,
chronic inflammation is recognized as a risk factor for developing several types of cancer, including gastric, intestinal, esophageal, prostate, and others.7
This article
summarizes the main aspects concerning gastric adenocarcinomas and the carcinogenic effects of H. pylori infection.
Classification and Pathology of Gastric Adenocarcinomas
Gastric adenocarcinoma is a heterogeneous disease. The most commonly used classification system in the US is the Lauren classification,9
which recognizes two main histologic types: intestinal
and diffuse (see Figure 1). Ten to 15% of gastric adenocarcinomas are mixed, containing features of both types. Although these two types seem to follow different precancerous processes and show clinical and
59
Macrophages, dendritic cells, and lymphocytes are effectors of the inflammatory role in the induction and promotion of the neoplastic process, mostly mediated by cytokines and chemokines.8
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