Helicobacter pylori infection and the risk of development of esophageal adenocarcinoma

Background. An increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these 2 phenomena are associated is unknown. Methods. We conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964-1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three randomly chosen control subjects from the MHC cohort were matched to each case subject, on the basis of age at the MHC, sex, race, and the date and site of the MHC. Data on cigarette smoking, alcohol consumption, body mass index (BMI), and education level were obtained at the MHC. Serum samples collected at the MHC were tested for IgG antibodies to H. pylori and to the H. pylori CagA protein. Results. Subjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma (odds ratio [OR], 0.37 [95% confidence interval (CI), 0.16-0.88]). This significant association was restricted to case subjects and control subjects <50 years old at the MHC (OR, 0.20 [95% CI, 0.06-0.68]). In patients with H. pylori infections, the OR for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. BMI >= 25 and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma. Conclusion. The absence of H. pylori infection, independent of cigarette smoking and BMI, is associated with a markedly increased risk of development of esophageal adenocarcinoma.