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Gastric Cancer: Understanding its Burden, Treatment Strategies, and Uncertainties in Management
Michael R. Page, PharmD, RPh; and Shriya Patel, PharmD
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David H. Ilson, MD, PhD

Gastric Cancer: Understanding its Burden, Treatment Strategies, and Uncertainties in Management

Michael R. Page, PharmD, RPh; and Shriya Patel, PharmD
Types of Gastric Cancer
There are 4 main types of gastric cancers, the most common by far of which is adenocarcinoma, diagnosed in 90% to 95% of cases. Adenocarcinomas typically develop in the mucosal layer and grow slowly.

The other gastric cancer types most often seen are lymphoma, gastrointestinal stromal tumors, and carcinoid tumors.2,13 Lymphomas account for approximately 4% of all gastric cancers. They have a heterogeneous pattern of pathogenesis and prognosis, with patient outcomes varying widely depending on the lymphoma’s specific characteristics. Even rarer are gastrointestinal stromal tumors, which form in a set of cells located in the stomach wall known as the interstitial cells of Cajal, and carcinoid tumors, which occur in hormone-producing cells of the stomach. Other cancer types that occur exceedingly rarely in the stomach include squamous cell carcinoma, small cell carcinoma, and leiomyosarcoma.2

Gastric Cancer and H. Pylori
Another factor associated with gastric cancer in certain populations is a high frequency of infection with H. pylori. Although it is not fully understood how H. pylori might increase the risk of gastric cancer, this rod-shaped helical bacterium has been classified since 1994 as a type I carcinogen by both the International Agency for Research on Cancer and the World Health Organization.11,14 Notably, H. pylori infection is most often associated with gastric cancers of the intestinal histologic subtype, which are observed more frequently in some areas of the world than others. Additionally, infection with H. pylori is not associated with all types of gastric cancer. H. pylori infection is only an independent risk factor for distal gastric cancer, and is not an independent risk factor for proximal forms of gastric cancer.5 Finally, although H. pylori infection is associated with 3- to 6-fold increase in the risk of developing gastric cancer, the vast majority of individuals infected with H. pylori—more than 99%—will never develop gastric cancer.5

The role of H. pylori in gastric cancer does not explain other epidemiologic factors and relationships. For example, risk factors for gastric cancer of the diffuse histologic subtype or of the cardia (a proximal form of gastric cancer) include higher socioeconomic class, obesity, and having type A blood.5,15 The complexity of gastric cancer epidemiologic factors point to an integrated understanding of the underlying causes.

Comorbidities associated with gastric cancer beyond H. pylori infection include adenomatous polyposis of the gastric tissue, chronic atrophic gastritis, intestinal metaplasia, and pernicious anemia. Other factors are related to diet, environment, occupation, and lifestyle. For example, frequent intake of heavily salted, smoked, and high-fat foods, in combination with low fruit and vegetable consumption, is a characteristic dietary pattern associated with gastric cancer. Smoking and frequent consumption of alcohol may also be related.1,5,10
Other Risk Factors for Gastric Cancer
Environmental factors—such as acidic agricultural soil; use of nitrate fertilizers; and increases in water-supply levels of nitrates, lead, or zinc—may also be associated with increased risk for gastric cancer. Workers in certain occupations, too, including mining and metallurgical work, may be at increased risk.5,10

Certain genetic factors increase risk. Specific mutated genes, such as MCC, APC, and p53, are found in a significant percentage of gastric cancer tumors. Another gene whose presence increases risk is cadherin-1 (CDH1), which is an adhesion molecule that depends on calcium and serves to facilitate binding of adjacent cells. The genetic locus that encodes E-cadherin, CDH1, is often mutated in families that have increased susceptibility to gastric cancer, possibly due to the CDH1 mutations causing increased permeability of cells.1,5,15

Other syndromes associated with gastric cancer include familial adenomatous polyposis, Cowden disease, hereditary diffuse gastric carcinoma, Li-Fraumeni syndrome, and hereditary nonpolyposis colorectal cancer syndrome. Many other genetic alterations are also often identified in gastric cancer with varying frequency.5

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