Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
BMJ Open. 2024 Jul 2;14(7):e079591. doi: 10.1136/bmjopen-2023-079591.
We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.
Retrospective cohort study.
This research was conducted at the national level, encompassing the entire population of Sweden.
This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years.
Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (HRA) use.
The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus HRA use.
Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance HRA users (IRR 1.05, 95% CI=0.87 to 1.27, <0.05).
Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.
我们旨在评估质子泵抑制剂（PPIs）长期使用与结直肠癌腺瘤（CRA）风险之间的关系，这是一项在全国范围内进行的大型队列研究。
回顾性队列研究。
本研究在全国范围内进行，涵盖了瑞典的全部人口。
该研究利用瑞典全国性登记处，确定了所有在 2005 年 7 月至 2012 年 12 月期间累积使用 PPI 至少 180 天的成年人，排除了随访时间不足 1 年的参与者。共纳入了 754118 名维持性 PPI 使用者，最长随访时间为 7.5 年。
维持性 PPI 使用（累积使用≥180 天），以维持性组胺 2 受体拮抗剂（HRA）使用作为对照。
主要结局指标是 CRA 的风险，以标准化发病率比（SIR）和 95%置信区间（CI）表示。进行了亚组分析，以探讨适应证、肿瘤部位、肿瘤分期和随访时间的影响。采用多变量泊松回归模型估计 PPI 与 HRA 使用的发病率比（IRR）和 95%CI。
与一般人群相比，男性和女性维持性 PPI 使用者的 CRA 风险略高（SIR 1.10，95%CI=1.06 至 1.13）。18-39 岁（SIR 2.79，95%CI=1.62 至 4.47）和 40-49 岁（SIR 2.02，95%CI=1.65 至 2.45）人群的风险明显高于一般人群。右侧 CRA 的风险高于一般人群（SIR 1.26，95%CI=1.20 至 1.32）。维持性 PPI 使用者和维持性 HRA 使用者的 CRA 风险无显著差异（IRR 1.05，95%CI=0.87 至 1.27，<0.05）。
维持性 PPI 使用可能与 CRA 风险增加有关，但需要更长的观察时间。
