The incidence of gastric cancer varies widely worldwide. The highest incidence (>20 per 100,000 in men) is seen in Japan, China, Eastern Europe, and South America, while the lowest incidence (<10 per 100,000 in men) is seen in Northern America, parts of Africa, and Northern Europe (1). In the United States, 24,590 new cases of gastric cancer are estimated in 2015, with 10,720 deaths (2). Gastric cancers occur at a median age of 69 years for men and 73 years for women (3). African Americans, Hispanic Americans, and Native Americans are 1.5 to 2.5 times more likely to develop gastric cancer than whites (3). In the United States, there are changing epidemiologic patterns regarding the anatomic location of esophagogastric cancers, with a trend of decreased occurrence of distal or noncardia gastric cancers (4). The reason for the decline is not known but may be related to change in dietary habits and food preservation. However, an increase in the incidence of gastric cardia cancers has been observed, from 2.4 cases per 100,000 individuals (1977-1981) to 2.9 cases per 100,000 individuals (2001-2006) in the white population (4). Similarly, the Surveillance, Epidemiology, and End Results (SEER) cancer registry program in the United States shows an approximate 2.5-fold increase in the incidence of gastroesophageal junction (GEJ) adenocarcinomas from 1973 to 1992, from 1.22 cases per 100,000 individuals (1973-1978) to 2.00 cases per 100,000 individuals (1985-1990), with rates stabilizing in the last two decades, with an incidence of 1.94 cases per 100,000 individuals (2003-2008) (3,5).
Population studies suggest that proximal cancers have a different pathogenesis than distal cancers (6). Potential causes of distal gastric cancers include Helicobacter pylori infection or E-cadherin expression loss, whereas proximal gastric cancers may behave similarly to distal esophageal and GEJ cancers, which progress from Barrett metaplasia to dysplasia to invasive adenocarcinoma. Only 26% of newly diagnosed gastric cancers are localized. The 5-year overall survival (OS) rate is 28.3%, which has not changed significantly over the past 30 to 40 years (1). Surgery is still the only chance for cure, and survival can be improved with multimodality therapy. The 5-year OS rate of patients with advanced disease remains dismal at less than 5%. Thus, despite decreasing incidence, gastric cancer remains a public health concern in the United States because of its high fatality rate.
Etiologic Characteristics and Risk Factors
The most frequent type of gastric cancer is adenocarcinoma, which consists of two main histologic variants: intestinal and diffuse. Intestinal-type gastric adenocarcinoma likely begins with an H pylori infection that leads to multistep progression (chronic active nonatrophic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia, and invasive adenocarcinoma) (7). More than 40% to 50% of distal gastric adenocarcinomas are associated with H pylori...