INTRODUCTION Proton pump inhibitors (PPIs) are commonly used for gastrointestinal disorders; given they increase the systemic levels of gastrin, a trophic hormone, there is a concern about their carcinogenicity. This study evaluated the associations PPI use and the risks of gastrointestinal cancers compared with the users. METHODS We performed a nested case-control study in a large, community-based integrated healthcare setting. Cases were adults with gastric (n = 1,233), colorectal (n = 18,595), liver (n = 2,329), or pancreatic cancers (n = 567). Each case was matched with up to 10 controls by age, sex, race/ethnicity, medical facility, and enrollment duration. The primary exposure was defined as ≥2-year cumulative PPI supply. Data were obtained from pharmacy, cancer registry, and electronic medical record databases. Associations were evaluated using conditional logistic regression and adjusted for multiple confounders. We also evaluated the cancer risks separately by PPI dose, duration of use, and dose and duration. RESULTS PPI use of ≥2-years was not associated with the risks of gastric (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.81-1.42), colorectal (OR: 1.05, 95% CI: 0.99-1.12), liver (OR: 1.14, 95% CI: 0.91-1.43), or pancreatic cancers (OR: 1.22, 95% CI: 0.89-1.67), compared with the users. In exploratory analyses, elevated cancer risks were primarily restricted to those with ≥10 years of PPI use, but no consistent associations were found for increasing PPI dose and/or duration of use. DISCUSSION PPI use of ≥2 years was not associated with increased risks of gastrointestinal cancers. The cancer risks associated with PPI use of ≥10 years were further studied.

中文翻译：

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社区人群中质子泵抑制剂的使用和胃癌、结直肠癌、肝癌和胰腺癌的风险

简介 质子泵抑制剂 (PPI) 常用于治疗胃肠道疾病。鉴于它们会增加胃泌素（一种营养激素）的全身水平，人们担心它们的致癌性。本研究评估了 PPI 使用与胃肠癌风险之间的关联，并与使用者进行了比较。方法 我们在一个大型的、基于社区的综合医疗机构中进行了一项巢式病例对照研究。病例为患有胃癌 (n = 1,233)、结直肠癌 (n = 18,595)、肝癌 (n = 2,329) 或胰腺癌 (n = 567) 的成人。每个病例根据年龄、性别、种族/民族、医疗设施和入组持续时间与多达 10 名对照者匹配。主要接触定义为≥2 年累积 PPI 供应。数据来自药房、癌症登记处和电子病历数据库。使用条件逻辑回归评估关联并针对多个混杂因素进行调整。我们还通过 PPI 剂量、使用持续时间以及剂量和持续时间分别评估了癌症风险。结果 ≥ 2 年的 PPI 使用与胃（比值比 [OR]：1.07，95% 置信区间 [CI]：0.81-1.42）、结直肠（OR：1.05，95% CI：0.99- 1.12)、肝癌 (OR: 1.14, 95% CI: 0.91-1.43) 或胰腺癌 (OR: 1.22, 95% CI: 0.89-1.67)，与使用者相比。在探索性分析中，癌症风险升高主要限于使用 PPI ≥ 10 年的患者，但未发现增加 PPI 剂量和/或使用持续时间的相关性。讨论 ≥2 年的 PPI 使用与胃肠道癌症风险增加无关。