质子泵抑制剂诱导胃癌风险研究进展

Research progress in the risk of gastric cancer induced by proton pump inhibitors

质子泵抑制剂(PPIs)是一种与H^(+)/K^(+)-ATP酶不可逆结合的强效抑酸药,主要用于治疗胃酸分泌过多引起的酸相关疾病。多项大型临床研究提示长期服用PPIs是胃癌的风险因素,且分子机制不清楚。现有研究显示PPIs参与胃癌高风险因素如高胃泌素血症、幽门螺旋杆菌二次感染和癌症相关靶基因及通路激活的调控,但目前尚无直接证据。因此本文对PPIs诱导胃癌风险的临床及机制研究进行总结,并结合近期对胃癌和癌旁转录组数据挖掘和组织芯片验证发现,系统阐述PPIs诱导胃癌的潜在机制,旨在明确PPIs与胃癌的相关性,并为深入研究PPIs诱导胃癌风险的分子机制提供新的思路和参考依据。

Proton pump inhibitors(PPIs) are a potent class of drugs that effectively reduce acid secretion in stomach by irreversibly binding to H^(+)/K^(+)-ATPase.They are commonly used to treat acid-related diseases caused by excessive acid secretion.However,a number of large clinical studies have suggested that long-term use of PPIs is a key risk factor for gastric cancer,and the molecular mechanisms are still unclear.Current research indicated that PPIs participate in the regulation of high-risk factors for gastric cancer,such as hypergastrinemia,secondary infection with Helicobacter pylori,and activation of cancer-related target genes and pathways.However,there is currently no direct evidence to support those findings.In this article,we summarized the clinical and mechanistic studies on the risk of gastric cancer associated with PPIs,and based on our recent findings from transcriptomic data mining and tissue microarray validation in gastric cancer and its surrounding tissues,we systematically elaborated the potential mechanisms of PPIs in inducing gastric cancer.The aim is to clarify the relationship between PPIs and gastric cancer,and provides new insights and reference for further molecular investigation into the risk of gastric cancer associated with PPIs.