Lessons from the epidemiology of Helicobacter pylori and cancer

Abstract

In 1994 the International Agency for Research on Cancer (IARC) declared Helicobacter pylori to be a type I carcinogen, a definite cause of cancer in humans¹. The strongest support for this assertion came from epidemiological studies solidly linking infection with the later development of malignancy. Bolstering these epidemiological findings are a series of laboratory studies demonstrating credible mechanisms for H. pylori-induced carcinogenesis, including: enhanced cell proliferation, induction of reactive oxygen species and intraepithelial formation of mutagenic oxidative DNA adducts^2–4. Similarities between gastric inflammation and other inflammatory precursors to cancer at other sites (e.g. schistosomiasis and hepatitis B infection) reinforce the likelihood for an H. pylori-gastric cancer link. Yet the IARC statement remains controversial, largely because epidemiological studies have not been completely consistent across all populations and because statistical associations are often viewed with some scepticism. In the years before and since the IARC statement, papers have been published refuting a role for H. pylori in adenocarcinoma^5,6. While some negative studies (particularly those presented as abstracts) are of dubious quality, others are well conducted and contain few obvious sources of bias. In this chapter, I will address the question: if H. pylori is so critical to gastric carcinogenesis, why do not all studies show an association?