Peptic ulcer as mediator of the association between risk of gastric cancer and socioeconomic status, tobacco smoking, alcohol drinking and salt intake

Background: Peptic ulcer disease (PUD) and gastric cancer (GC) are more prevalent in individuals with low socioeconomic status (SES) and share several risk factors. The aim of this study was to investigate the mediating role of PUD in the association between established risk factors and GC. Methods: We conducted a pooled analysis of 12 studies from the Stomach Cancer Pooling Project Consortium, including a total of 4877 GC cases and 11 808 controls. We explored the mediating role of PUD in the association between SES, tobacco smoking, heavy alcohol drinking and salt intake, and GC. Also, we assessed the ORs and 95% CIs of the risk factors and both PUD and GC. Results: PUD mediated 36% of the smoking effect mainly among men. Other risk factors were only slightly mediated by PUD (SES, 5.3%; heavy alcohol drinking, 3.3%; and salt intake, 2.5%). No significant difference was found when excluding PUD diagnosed within 2 years from GC. Conclusions: Our study provides innovative information on the mechanism of stomach mucosal damage leading to PUD and GC, with respect to the effect of tobacco smoking in particular.