Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts

Abstract

Background: The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circulating antibody response can be lost with development of cancer; thus retrospective studies are subject to bias resulting from classification of cases as H pylori negative when they were infected in the past.

Aims: To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with H pylori infection. To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis.

Methods: Studies were eligible if blood samples for H pylori serology were collected before diagnosis of gastric cancer in cases. Identified published studies and two unpublished studies were included. Individual subject data were obtained for each. Matched odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the association between H pylori and gastric cancer.

Results: Twelve studies with 1228 gastric cancer cases were considered. The association with H pylori was restricted to non-cardia cancers (OR 3.0; 95% CI 2.3-3.8) and was stronger when blood samples for H pylori serology were collected 10+ years before cancer diagnosis (5.9; 3.4-10.3). H pylori infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7-1.4).

Conclusions: These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with H pylori infection and that H pylori does not increase the risk of cardia cancer. They also support the idea that when H pylori status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated.

Figure 1

Matched odds ratios (OR) and 95% confidence intervals (CI) for the association between Helicobacter pylori infection and gastric cancer, overall and by study. The area of the square is proportional to the study size. The diamond shows the OR value for all studies combined, with 95% CI represented by the horizontal points. ⁺Unpublished data.

Figure 2

Matched odds ratios (OR) and 95% confidence intervals (CI) for the association between Helicobacter pylori infection and non-cardia gastric cancer, overall and by study. The area of the square is proportional to the study size. The diamond shows the OR value for all studies combined, with 95% CI represented by the horizontal points. ⁺Unpublished data.

Figure 3

Matched odds ratios (OR) and 95% confidence intervals (CI) for the association between Helicobacter pylori infection and cardia cancer, overall and by study. The area of the square is proportional to the study size. The diamond shows the OR value for all studies combined, with 95% CI represented by the horizontal points. ⁺Unpublished data.