Morris Maeve T, Duncan Benjamin C, Piazuelo M Blanca, Olfert I Mark, Xu Xiaojiang, Hussain Salik, Peek Richard M, Busada Jonathan T
Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Cancer Prev Res (Phila). 2025 May 1;18(5):271-281. doi: 10.1158/1940-6207.CAPR-24-0378.
Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Chronic infection by the bacterium Helicobacter pylori is the most prominent gastric cancer risk factor, but only 1% to 3% of infected individuals will develop gastric cancer. Cigarette smoking is another independent gastric cancer risk factor, and H. pylori-infected smokers are at a 2- to 11-fold increased risk of gastric cancer development, but the direct impacts of cigarette smoke (CS) on H. pylori pathogenesis remain unknown. In this study, male C57BL/6 mice were infected with H. pylori and began smoking within 1 week of infection. The mice were exposed to CS 5 days/week for 8 weeks. CS exposure had no notable impact on gross gastric morphology or inflammatory status compared with filtered-air (FA) exposed controls in mock-infected mice. However, CS exposure significantly blunted H. pylori-induced gastric inflammatory responses, reducing gastric atrophy and pyloric metaplasia development. Despite blunting these classic pathological features of H. pylori infection, CS exposures increased DNA damage within the gastric epithelial cells and accelerated H. pylori-induced dysplasia onset in the INS-GAS gastric cancer model. These data suggest that cigarette smoking may clinically silence classic clinical symptoms of H. pylori infection but enhance the accumulation of mutations and accelerate gastric cancer initiation. Prevention Relevance: These findings suggest that cigarette smoking suppresses pathophysiological hallmarks of H. pylori infection while accelerating gastric carcinogenesis. Therefore, smokers should receive screening for H. pylori infection to reduce gastric cancer risk. See related Spotlight, p. 257.
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%至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（CS）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1周内开始吸烟。小鼠每周5天暴露于香烟烟雾中，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，暴露于香烟烟雾对胃的大体形态或炎症状态没有显著影响。然而，暴露于香烟烟雾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，暴露于香烟烟雾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不明显，但会增加突变积累并加速胃癌的发生。预防相关性：这些发现表明，吸烟在抑制幽门螺杆菌感染的病理生理特征的同时，加速了胃癌的发生。因此，吸烟者应接受幽门螺杆菌感染筛查，以降低患胃癌的风险。见相关聚焦文章，第257页。
