39-10: Gastric Adenocarcinoma

GENERAL CONSIDERATIONS

Gastric adenocarcinoma is the third most common cause of cancer death worldwide. However, its incidence has declined rapidly over the last 70 years, especially in Western countries, which may be attributable to changes in diet (more fruits and vegetables), food refrigeration (allowing more fresh foods and reduced salted, smoked, and preserved foods), reduced toxic environmental exposures, and a decline in Helicobacter pylori infections. The incidence of gastric cancer remains high (62/100,000 males) in Japan and many developing regions, including eastern Asia, Eastern Europe, Chile, Colombia, and Central America. In the United States, there were an estimated 27,600 new cases and 11,010 deaths in 2020. The incidence is higher in Asian Americans, Hispanics, African Americans, and Native Americans (including Native Alaskans).

There are two main histologic variants of gastric cancer: “intestinal-type” (which resembles intestinal cancers in forming glandular structures) and “diffuse” (which is poorly differentiated, has signet-ring cells, and lacks glandular formation). The incidence of intestinal-type gastric cancer has declined significantly, but it is still the more common type (70–80%); it occurs twice as often in men as women, primarily affects older people (mean age 68 years), and is more strongly associated with environmental factors. It is believed to arise through a gradual, multi-step progression from inflammation (most commonly due to H pylori), to atrophic gastritis, to intestinal metaplasia, and finally to dysplasia and cancer. Chronic H pylori gastritis is the strongest risk factor for gastric carcinoma, increasing the relative risk 3.5- to 20-fold. It is estimated that 60–90% of cases of gastric carcinomas may be attributable to H pylori. Other risk factors for intestinal-type gastric cancer include pernicious anemia, a history of partial gastric resection more than 15 years previously, smoking, and diets that are high in nitrates or salt and low in vitamin C. Diffuse gastric cancer accounts for 20–30% of gastric cancer cases. In contrast to intestinal-type cancer, it affects men and women equally, occurs more commonly in young people, is not as strongly related to H pylori infection, and has a worse prognosis than intestinal-type cancer due to early metastasis. Most diffuse gastric cancers are attributable to acquired or hereditary mutations in the genes regulating the E-cadherin cell adhesion protein. Hereditary diffuse gastric cancer accounts for 1–3% of gastric cancers. The cancer may arise at a young age, is often multifocal and infiltrating with signet ring cell histology, and confers poor prognosis. Many of these families have a germline mutation of E-cadherin CDH1, which is inherited in an autosomal dominant pattern and carries a greater than 60% lifetime risk of gastric cancer. Individuals with the CDH1 mutation are also at very high risk for developing breast cancer, and the risk begins at an early age. Prophylactic gastrectomy should be considered in ...