Chronic cigarette smoke exposure masks pathological features ofHelicobacter pyloriinfection while promoting tumor initiation

Abstract

AbstractGastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacteriumHelicobacter pyloriis the most prominent gastric cancer risk factor, but only 1-3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, andH. pylori-infected smokers are at a 2-11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke onH. pyloripathogenesis remain unknown. In this study, male C57BL/6 mice were infected withH. pyloriand began smoking within one week of infection. The mice were exposed to cigarette smoke (CS) five days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared to filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly bluntedH. pylori-induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features ofH. pyloriinfection, CS exposures increased DNA damage within the gastric epithelial cells and acceleratedH. pylori-induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms ofH. pyloriinfection but enhance the accumulation of mutations and accelerate gastric cancer initiation.