Objective: Helicobacter pylori infection is the most important risk factor for gastric cancer, but no association with cardia cancer has been recognized. However, a heterogeneous distribution of etiologically distinct types of cardia cancer may contribute to explain conflicting findings between studies in high- and low-risk settings. We aimed to quantify the association between H. pylori infection and gastric cardia cancer through meta-analysis, and to provide an explanation for the expected heterogeneity of results.
Methods: We systematically reviewed published studies addressing the association between H. pylori infection and gastric cardia cancer (up to June 2009), and extracted relative risk (RR) estimates for the association with cardia and non-cardia cancers. Summary RR estimates and 95% confidence intervals (95% CI) were computed using random-effects models. Subgroup analyses were conducted, namely according to gastric cancer risk settings.
Results: Thirty-four articles were considered for meta-analysis. For cardia cancer, summary RR was 1.08 (95% CI 0.83-1.40; I (2) = 52.8%), higher in high-risk (RR = 1.98; 95% CI 1.38-2.83; I (2) = 18.4%) than in low-risk settings (RR = 0.78; 95% CI 0.63-0.97; I (2) = 11.6%). For non-cardia cancer, RR estimates were similar in high- (RR = 3.02; 95% CI 1.92-4.74; I (2) = 90.7%) and low-risk settings (RR = 2.56; 95% CI 1.99-3.29; I (2) = 46.6%). These observations were consistent across different inclusion criteria and when accounting for the virulence of the infecting strains.
Conclusions: In high-risk settings, a positive association between H. pylori infection and gastric cancer was observed both for cardia and non-cardia cancers. The results support the hypothesis of a heterogeneous distribution of etiologically distinct types of cardia cancer.