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Background: Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma.

Methods: This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay.

Results: Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0).

Conclusions: Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved. (N Engl J Med 1994;330:1267-71.)

Owned, published, and (C) copyrighted, 1994, by the MASSACHUSETTS MEDICAL SOCIETY