Individual and joint contribution of family history and Helicobacter pylori infection to the risk of gastric carcinoma

Background: Helicobacter pylori infection and a positive family history of gastric carcinoma have been identified as risk factors for the disease. It is unclear, however, to what degree their impact on the risk of gastric carcinoma is independent, because H. pylori also clusters within families.

Methods: The authors carried out a population-based, statewide case-control study in Saarland, Germany, to assess the individual and joint contributions of family history and H. pylori infection to the risk of gastric carcinoma. Cases included 68 patients with histologically verified gastric carcinoma. Controls included 239 patients with colorectal carcinoma who were matched to the cases by age and gender. Information on family history (defined as gastric carcinoma in at least one first-degree relative) and potential confounders was collected by standardized interviews. Immunoglobulin G antibodies against H. pylori were measured by enzyme-linked immunosorbent assay. In addition, antibodies against the CagA antigen were determined by Western blot analysis.

Results: H. pylori infection and family history were positively related, and both risk factors were more common among cases than among controls. Although the association between family history and gastric carcinoma was somewhat reduced by control for H. pylori infection, both risk factors still showed strong independent relations with gastric carcinoma after control for each other. Compared with uninfected subjects who had no family history, subjects with both a positive family history and infection with a CagA positive H. pylori strain had a more than 8-fold total risk of gastric carcinoma (adjusted odds ratio [OR], 8.2; 95% confidence interval [CI], 2.2-30.4) and a 16-fold risk of noncardia gastric carcinoma (OR, 16.0; 95% CI, 3.9-66.4).

Conclusions: Infection with CagA positive H. pylori strains and a positive family history appear to be strong independent risk factors for gastric carcinoma. They may be useful markers for identifying subjects at high risk for the disease and for targeting efforts of prevention and early detection.