Brusselaers Nele, Wahlin Karl, Engstrand Lars, Lagergren Jesper
Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
BMJ Open. 2017 Oct 30;7(10):e017739. doi: 10.1136/bmjopen-2017-017739.
Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs. Concerns have been raised about a potentially increased risk of gastric cancer following long-term use. Our aim is to assess the risk of gastric cancer associated with PPI use, taking into account underlying indications.
This is a population-based cohort study. Standardised incidence ratios (SIRs) and 95% CIs were calculated to compare the risk of gastric cancer among long-term PPI users with the corresponding background population, while taking confounding by indication into account.
Population-based study in Sweden (2005-2012).
This study included virtually all adults residing in Sweden exposed to maintenance therapy with PPIs.
EXPOSURE/INTERVENTION: Maintenance use of PPIs, defined as at least 180 days during the study period. Maintenance use of histamine 2 receptor antagonist was evaluated for comparison reasons.
Gastric cancer (cardia and non-cardia), and subgroup analysis for gastric adenocarcinoma, as defined by the Swedish Cancer Registry.
Among 797 067 individuals on maintenance PPI therapy, the SIR of gastric cancer was over threefold increased (SIR=3.38, 95% CI 3.23 to 3.53). Increased SIRs were found in both sexes and all age groups, but were especially increased among PPI users younger than 40 years (SIR=22.76, 95% CI 15.94 to 31.52). Increased SIRs were found for each indication studied, including those without an association with gastric cancer, for example, gastro-oesophageal reflux (SIR=3.04, 95% CI 2.80 to 3.31), and those with a supposedly decreased risk, for example, aspirin users (SIR=1.93, 95% CI 1.70 to 2.18). The association was similar for cardia and non-cardia gastric cancer. Analyses restricted to adenocarcinoma showed similar results to those for all gastric cancers. Long-term users of histamine 2 receptor antagonists, which have the same indications as PPIs, were not at any increased risk.
Long-term PPI use might be an independent risk factor for gastric cancer. This challenges broad maintenance PPI therapy, particularly if the indication is weak.
质子泵抑制剂（PPIs）是最常用的处方药之一。长期使用后胃癌风险可能增加，这引发了人们的担忧。我们的目的是评估使用PPIs相关的胃癌风险，并考虑潜在的适应症。
这是一项基于人群的队列研究。计算标准化发病率比（SIRs）和95%置信区间（CIs），以比较长期使用PPIs的人群与相应背景人群患胃癌的风险，同时考虑适应症的混杂因素。
瑞典的一项基于人群的研究（2005 - 2012年）。
本研究几乎纳入了瑞典所有接受PPIs维持治疗的成年人。
暴露/干预：PPIs的维持使用，定义为研究期间至少180天。为了进行比较，评估了组胺2受体拮抗剂的维持使用情况。
瑞典癌症登记处定义的胃癌（贲门癌和非贲门癌），以及胃腺癌的亚组分析。
在797067名接受PPIs维持治疗的个体中，胃癌的SIR增加了三倍多（SIR = 3.38，95% CI 3.23至3.53）。男女和所有年龄组的SIR均升高，但40岁以下的PPI使用者中升高尤为明显（SIR = 22.76，95% CI 15.94至31.52）。在所研究的每种适应症中均发现SIR升高，包括那些与胃癌无关联的适应症，例如胃食管反流（SIR = 3.04，95% CI 2.80至3.31），以及那些据推测风险降低的适应症，例如阿司匹林使用者（SIR = 1.93，95% CI 1.70至2.18）。贲门癌和非贲门癌的关联相似。仅限于腺癌的分析结果与所有胃癌的结果相似。与PPIs有相同适应症的组胺2受体拮抗剂的长期使用者没有任何风险增加。
长期使用PPIs可能是胃癌的一个独立危险因素。这对广泛的PPIs维持治疗提出了挑战，特别是如果适应症不明确。
