H. pylori—What Makes It a Friend or Foe in Cancer Risk?

How does infection with Helicobacter pylori (H. pylori) increase risk for gastric cancer but reduce risk for esophageal cancers? One proposed mechanism is that H. pylori induces gastric atrophy and hypochlorhydria—these promote gastric cancer but reduce acid exposure to the lower esophagus, which protects against esophageal adenocarcinoma. However, many people with H. pylori infections do not develop gastric cancer and others are not protected from esophageal cancers. What modifiers of risk, such as genetic and environmental factors, are involved?

Illustration of H. pylori

In the July issue of Gastroenterology, David C. Whiteman et al. investigated the mechanisms by which H. pylori infection promotes and prevents cancer, comparing data from almost 800 patients with esophageal cancers with that from about 1300 control participants. They associated H. pylori infection with a more than 2-fold reduction in adenocarcinomas (but not squamous cell cancer) of the esophagus.

Previous studies associated polymorphisms that affect expression of the pro-inflammatory cytokines interleukin (IL)-1B and tumor necrosis factor (TNF)-a with gastric atrophy, reduced stomach acid, and increased risk for gastric cancer in individuals with H. pylori infection. However, Whiteman et al. found no evidence that these polymorphisms modified the association between H. pylori and esophageal cancers. Nor did environmental factors, such as smoking or use of proton pump inhibitors, affect the association.

So, does H. pylori infection reduce esophageal cancer risk by mechanisms beyond inflammation and gastric acid production? Whiteman et al. performed their study in an Australian population; Australians have a low prevalence of H. pylori infection, and the gastric phenotypes of the study participants were not determined, so it is not clear if they had all the features of H. pylori infection that affect cancer risk. It is also possible that expression of other mediators of inflammation, such as the IL-1 receptor, is involved.

Further studies are required to clarify the role of H.pylori-induced inflammation in GI cancer susceptibility; alterations in the microbial flora or expression of hormones such as ghrelin or leptin might affect carcinogenesis. Nonetheless, the interaction between H. pylori infection and cancer risk are clear—as incidence of infection decreases among developed countries, incidence of esophageal adenocarcinoma continues to increase.

Whiteman DC, Parmar P, Fahey P, et al. Association of Helicobacter pylori infection with reduced risk for esophageal cancer is independent of environmental and genetic modifiers. Gastroenterology 2010;139:73-83.

Read the article online at Gastroenterology. This article has accompanying CME.

Read the accompanying editorial:
McLean MH and El-Omar E. Esophageal cancers and Helicobacter pylori: do host genes matter? Gastroenterology 2010;139:17-19.