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

Background-The magnitude of the association between Helicobacter pylori and incidence of gastric cancer is unclear. H pylori infection and the circula ting antibody response can be lost with development of cancer; thus retrosp ective studies are subject to bias resulting from classification of cases a s H pylori negative when they were infected in the past. Aims-To combine data from all case control studies nested within prospectiv e cohorts to assess more reliably the relative risk of gastric cancer assoc iated 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 c ollected 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 Identified published studies and two unpublished studies were included.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 interv als (95% CI) were calculated for the association between H pylori and gastr ic 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 infe ction 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 rela tive 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.