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

<jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p> The magnitude of the association between <jats:italic>Helicobacter pylori</jats:italic> and incidence of gastric cancer is unclear. <jats:italic>H pylori</jats:italic> 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 <jats:italic>H pylori</jats:italic> negative when they were infected in the past. </jats:p> </jats:sec> <jats:sec> <jats:title>AIMS</jats:title> <jats:p> To combine data from all case control studies nested within prospective cohorts to assess more reliably the relative risk of gastric cancer associated with <jats:italic>H pylori</jats:italic> infection. To investigate variation in relative risk by age, sex, cancer type and subsite, and interval between blood sampling and cancer diagnosis. </jats:p> </jats:sec> <jats:sec sec-type="methods"> <jats:title>METHODS</jats:title> <jats:p> Studies were eligible if blood samples for <jats:italic>H pylori</jats:italic> 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 Identified published studies and two unpublished studies were included.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 <jats:italic>H pylori</jats:italic> and gastric cancer. </jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p> Twelve studies with 1228 gastric cancer cases were considered. The association with <jats:italic>H pylori</jats:italic> was restricted to non-cardia cancers (OR 3.0; 95% CI 2.3–3.8) and was stronger when blood samples for <jats:italic>H pylori</jats:italic> serology were collected 10+ years before cancer diagnosis (5.9; 3.4–10.3). <jats:italic>H pylori</jats:italic> infection was not associated with an altered overall risk of cardia cancer (1.0; 0.7–1.4). </jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p> These results suggest that 5.9 is the best estimate of the relative risk of non-cardia cancer associated with <jats:italic>H pylori</jats:italic> infection and that <jats:italic>H pylori</jats:italic> does not increase the risk of cardia cancer. They also support the idea that when <jats:italic>H pylori</jats:italic> status is assessed close to cancer diagnosis, the magnitude of the non-cardia association may be underestimated. </jats:p> </jats:sec>