Risk Factors and Precancerous Conditions for Gastric Cancer: Implications and Management

Key Takeaways:

• Gastric cancer is the third leading cause of cancer-related deaths worldwide, with risk factors for the majority of cases being environmental in nature

• Helicobacter pylori infection is the most common risk factor for gastric cancer, followed by a high-salt intake, alcohol consumption, smoking, obesity, and a prior history of gastric cancer, with these risk factors responsible for approximately 97% of all cases 

• About 3% of gastric cancers are thought to have a familial aspect

• Approximately 50% of the world’s population is positive for H pylori infection, with 88% to 90% of these individuals being asymptomatic, 10% developing a peptic ulcer, and 1-3% developing gastric cancer

• Gastric cancer can be divided into two types:

  • Diffuse gastric cancer does not have an identifiable sequence  

  • Intestinal gastric cancer is associated with a known sequence of epithelial changes, from chronic gastritis to chronic atrophic gastritis to intestinal metaplasia to dysplasia to gastric cancer

• With targeted and early eradication of H pylori infection—that is, prior to the development of intestinal metaplasia—a decrease of about 50% in the development of gastric cancer has been noted 

• In patients with intestinal metaplasia, an endoscopy should be performed every 3-5 years

Gastric cancer is the third most common cause of cancer-related deaths worldwide.^[1] The majority of these cancers have risk factors that are environmental. The most common risk factor is H pylori, followed by dietary risk factors of a high-salt diet, as well as alcohol; smoking; obesity; as well as a prior history of having a gastric cancer. Those risk factors make up roughly 97% of gastric cancers. Roughly 3% are felt to be familial. 

The difficulty with H pylori being a major risk factor is that roughly half of the world's population is positive for H pylori.^[2] The vast majority of those—88-90%—are asymptomatic. Roughly 10% of those will develop peptic ulcer, and roughly 1-3% will develop gastric cancer. So, the vast majority of patients with H pylori have no risk or very low risk for developing gastric cancer. 

We know H pylori is necessary, but not alone, to cause gastric cancer. There have to be other hits that occur to go on the cascade to produce cancer. There are two types of gastric cancer: There's the diffuse cancer, which does not have an identifiable sequence; and there is the intestinal type, which has a known sequence of epithelial changes, beginning with chronic gastritis, develop[ing] into chronic atrophic gastritis, which develops into intestinal metaplasia, then dysplasia, then cancer. That's a known precancer sequence that's been well established. 

H pylori plays a role, and the H pylori causes both chronic gastritis and chronic atrophic gastritis. In the right patients, if we can target and eradicate H pylori early, there's been shown to be a 50% decrease in development of gastric cancer. But that's only in patients where you can identify the changes before they develop into intestinal metaplasia. If you find H pylori early, when the patient has just gastritis, eradicating H pylori can decrease the incidence of gastric cancer. Once you develop metaplasia, however, even with eradicating H pylori, that cancer risk persists. 

The risk of intestinal metaplasia is low, but it definitely is a precursor to the dysplasia cascade. The exact screening guidelines aren't known. But the feeling is [that] doing endoscopies on an every 3- to 5-year basis with existing metaplasia is a reasonable approach to screen for and prevent the development of gastric cancer.