Morris Maeve T, Piazuelo M Blanca, Olfert I Mark, Xu Xiaojiang, Hussain Salik, Peek Richard M, Busada Jonathan T
bioRxiv. 2024 Aug 7:2024.08.05.604297. doi: 10.1101/2024.08.05.604297.
Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacterium is 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, and infected smokers are at a 2-11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke on pathogenesis remain unknown. In this study, male C57BL/6 mice were infected with and 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 blunted induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features of infection, CS exposures increased DNA damage within the gastric epithelial cells and accelerated induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms of infection but enhance the accumulation of mutations and accelerate gastric cancer initiation.
胃癌是全球第五大常见癌症，也是癌症死亡的第五大主要原因。幽门螺杆菌的慢性感染是最突出的胃癌危险因素，但只有1%-3%的感染者会患上胃癌。吸烟是另一个独立的胃癌危险因素，感染幽门螺杆菌的吸烟者患胃癌的风险增加2至11倍，但香烟烟雾对幽门螺杆菌发病机制的直接影响尚不清楚。在本研究中，雄性C57BL/6小鼠感染幽门螺杆菌，并在感染后一周内开始吸烟。小鼠每周5天暴露于香烟烟雾（CS）中，持续8周。与假感染小鼠中暴露于过滤空气（FA）的对照组相比，CS暴露对胃大体形态或炎症状态没有显著影响。然而，CS暴露显著减弱了幽门螺杆菌诱导的胃炎症反应，减少了胃萎缩和幽门化生的发生。尽管CS暴露减弱了幽门螺杆菌感染的这些经典病理特征，但在INS-GAS胃癌模型中，CS暴露增加了胃上皮细胞内的DNA损伤，并加速了幽门螺杆菌诱导的发育异常的发生。这些数据表明，吸烟可能在临床上使幽门螺杆菌感染的经典临床症状消失，但会增加突变的积累并加速胃癌的发生。
