Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Shantou University Medical College, Shantou 515041, China.
Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Eur J Cancer. 2021 Oct;156:190-201. doi: 10.1016/j.ejca.2021.07.030. Epub 2021 Sep 1.
For the past two decades, dispute on whether proton pump inhibitor (PPI) leads to digestive tract cancer remains, and emerging studies in recent years still demonstrate inconsistent results, which continues to perpetuate concerns over the safety of PPI use. We performed a systematic review and meta-analysis, with comprehensive evaluation by Bradford Hill criteria of causation, to assess the effect of PPI use on digestive tract cancers.
Medline, Embase and Web of Science databases were searched for observational studies published up to 15th January 2021. Pooled relative risks (RRs) were estimated via random effects models. Cumulative defined daily dose- and duration-risk relationships using restricted cubic spline and fractional polynomial models were investigated. Bradford Hill criteria were applied to evaluate causation. PROSPERO Registration: CRD42020211103.
Thirty-two publications containing 4,355,254 participants were included. PPI use is associated with an increased risk of overall digestive tract cancers (RR = 1.63, 95% confidence interval (CI) 1.33 to 2.00). PPI use is correlated with increased risks of gastric cancer (RR = 1.78, 95% CI 1.38 to 2.31), pancreatic cancer (RR = 1.72, 95% CI 1.05 to 2.82) and liver cancer (RR = 1.62, 95% CI 1.04 to 2.52), but not of esophageal cancer (RR = 2.06, 95% CI 0.65 to 6.57) and colorectal cancer (RR = 1.24, 95% CI 0.93 to 1.66). The association between PPI and digestive tract cancers is stronger in people with minimal exposure. When cumulative defined daily dose or duration increases, the risks decline and become non-significant. Evaluation by Bradford Hill criteria indicates weak evidence of causation.
A causal relationship between PPI use and digestive tract cancers is not supported by the evidence in the current review. Concerns over carcinogenic side-effects of PPI might be unfounded.
在过去的二十年中，质子泵抑制剂（PPI）是否会导致消化道癌症一直存在争议，近年来的新兴研究结果仍不一致，这继续引发了人们对 PPI 使用安全性的担忧。我们进行了系统评价和荟萃分析，并通过因果关系的布拉德福·希尔标准进行了全面评估，以评估 PPI 使用与消化道癌症的关系。
检索了截至 2021 年 1 月 15 日发表的观察性研究的 Medline、Embase 和 Web of Science 数据库。通过随机效应模型估计汇总相对风险（RR）。使用限制性立方样条和分数多项式模型研究累积定义日剂量和持续时间风险关系。应用布拉德福·希尔标准评估因果关系。PROSPERO 注册：CRD42020211103。
共纳入 32 篇文献，包含 4355254 名参与者。PPI 使用与总体消化道癌症风险增加相关（RR=1.63，95%置信区间（CI）1.33 至 2.00）。PPI 使用与胃癌（RR=1.78，95%CI 1.38 至 2.31）、胰腺癌（RR=1.72，95%CI 1.05 至 2.82）和肝癌（RR=1.62，95%CI 1.04 至 2.52）风险增加相关，但与食管癌（RR=2.06，95%CI 0.65 至 6.57）和结直肠癌（RR=1.24，95%CI 0.93 至 1.66）无关。在暴露最少的人群中，PPI 与消化道癌症之间的关联更强。当累积定义日剂量或持续时间增加时，风险下降且变得不显著。通过布拉德福·希尔标准评估表明因果关系的证据较弱。
目前的综述结果不支持 PPI 使用与消化道癌症之间存在因果关系。对 PPI 致癌副作用的担忧可能是没有根据的。
