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Gastric Cancer: Local and Global Burden
Lynne Lederman, PhD
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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
Gastric cancer is estimated to be the fifth most frequently diagnosed cancer in the world, and the third leading cause of cancer-related death. In the United States alone, gastric cancer is responsible for more than 26,000 diagnoses and nearly 11,000 deaths each year. Both new diagnoses and deaths occur disproportionately in men, most often in older patients. The average age of diagnosis in patients with stomach cancer is 69 years, with more than half (60%) of diagnoses occurring in those 65 years or older. Although rates of gastric cancer have been declining around the world since the late 1930s, disparities in the incidence and prevalence of gastric cancer among countries indicate that there are potential important differences in genetics and lifestyle that may be contributing factors.1,3-5

In the United States, gastric cancer is a relatively uncommon cancer type with the lifetime risk of developing stomach cancer estimated at less than 1%, far lower than in other countries.1,2 Of the more than 1.4 million new cancer cases that occur each year in the United States, gastric cancer accounts for approximately 1.5%.4 The United States incidence of gastric cancer has fallen dramatically since the 1930s, when the estimated incidence was 35 cases per 100,000 individuals in the population per year. By 2003, the incidence had fallen nearly 10-fold, with approximately 4 cases diagnosed per 100,000 individuals per year (Figure 14).2,5

Although the factors behind the lowered gastric cancer risk are not fully understood, they may relate to an increased availability of refrigeration, which has both increased the availability of fruits and vegetables and reduced intake of salted or smoked foods. Other factors may include the use of antibiotics, which may kill Helicobacter pylori (H. pylori) bacteria in the stomach, a potential contributing factor in some stomach cancer cases.1,2,6
The Heterogeneous Nature of Gastric Cancers
Understanding gastric cancer begins with knowledge of the stomach’s 5 parts: cardia, fundus, corpus (or body), antrum, and pylorus. Together, the cardia, fundus, and corpus are known as the proximal stomach, located towards the top of the stomach, closest to the esophagus. These 3 stomach parts produce acid and digestive enzymes, as well as intrinsic factor, which is critical for absorption of vitamin B12. The 2 lower areas, the antrum and pylorus, are collectively known as the distal stomach (Figure 22,7).2,7

The stomach’s anatomy also includes its 5-layer wall. The mucosa is the innermost layer, followed by the submucosa, the muscularis propria, the subserosa, and then the outermost layer, the outer serosa. The outer serosa serves a protective function, and the muscularis propia mixes and agitates stomach contents. The mucosa produces digestive enzymes and acids, and this is where gastric cancers typically originate.2,8 As gastric cancer progresses, abnormal cells progress from inner layers of the stomach to outer layers of the stomach. As stomach cancer infiltrates the outer layers of the stomach, prognosis worsens.1,2
Geographic Trends in Gastric Cancer
Examination of the age-adjusted death rate per 100,000 individuals in the population by country makes apparent that certain regions of the world—Russia, Eastern Europe, and parts of Asia—are more prone to a high incidence and prevalence of gastric cancer. Conversely, North America, Africa, the United Kingdom, Australia, and New Zealand have the lowest rates of gastric cancer.1,5,9

Japanese men have the highest incidence rate of gastric cancer in the world, with 116 cases occurring per 100,000 individuals. Of all new cancer diagnoses, nearly 1 in 5 new cancers diagnosed in Japan are gastric cancers.5,9 In considering incidence by country, including both genders, the overall incidence of gastric cancer is highest in China.1 Gastric cancer is rarely diagnosed early in the disease, with most diagnoses occurring late, in the advanced stages of disease.1

Just as the incidence and prevalence of gastric cancer vary regionally, rates of gastric cancer vary by ethnic population. For example, in the United States, the incidence of gastric cancer is 21.6 cases per 100,000 among those of Native American ancestry, and 20 cases per 100,000 in those of Asian background. However, the 5-year overall survival rate in patients of all ethnic backgrounds who develop gastric cancer does not vary substantially.4,5,10

Although the incidence of gastric cancer varies internationally, incidence rates do not necessarily correlate to mortality. In European Union countries, for example, mortality rates are higher than in non-Western populations, because gastric cancer is encountered more commonly in non-Western populations and thus is often detected earlier in the disease process. Delayed diagnosis of gastric cancer in Western populations contributes to the presence of later-stage disease at initial diagnosis, resulting in increased rates of mortality, despite its lower incidence and prevalence.1,5,11

Gastric cancers may also be classified by their histologic characteristics: undifferentiated (intestinal-type histology) or well differentiated and diffuse. Importantly, the incidence of diffuse histologic cell types in gastric cancer is observed with approximately equal incidence and prevalence throughout the world, and is associated with diffuse gastritis without tissue atrophy. Gastric cancers with histologic characteristics of an intestinal type are observed more frequently in areas with abnormally high incidence and prevalence of gastric cancer. Gastric cancers of an intestinal subtype predictably progress from metaplasia to cancer in a well-characterized step-wise process.5,12

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