Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada.
Gut. 2022 Jan;71(1):111-118. doi: 10.1136/gutjnl-2021-325096. Epub 2021 Jul 1.
To determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs).
The United Kingdom Clinical Practice Research Datalink was used to identify initiators of PPIs and H2RA from 1990 to 2018, with follow-up until 2019. Cox proportional hazards models were fit to estimate marginal HRs and 95% CIs of colorectal cancer. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Prespecified secondary analyses assessed associations with cumulative duration, cumulative dose and time since treatment initiation. The number needed to harm was calculated at five and 10 years of follow-up.
The cohort included 1 293 749 and 292 387 initiators of PPIs and H2RAs, respectively, followed for a median duration of 4.9 years. While the use of PPIs was not associated with an overall increased risk of colorectal cancer (HR: 1.02, 95% CI 0.92 to 1.14), HRs increased with cumulative duration of PPI use (<2 years, HR: 0.93, 95% CI 0.83 to 1.04; 2-4 years, HR: 1.45, 95% CI 1.28 to 1.60; ≥4 years, HR: 1.60, 95% CI 1.42 to 1.80). Similar patterns were observed with cumulative dose and time since treatment initiation. The number needed to harm was 5343 and 792 for five and 10 years of follow-up, respectively.
While any use of PPIs was not associated with an increased risk of colorectal cancer compared with H2RAs, prolonged use may be associated with a modest increased risk of this malignancy.
与组胺 2 受体拮抗剂 (H2RA) 相比，确定质子泵抑制剂 (PPI) 是否会增加结直肠癌的风险。
利用英国临床实践研究数据链接，从 1990 年至 2018 年识别 PPI 和 H2RA 的使用者，并随访至 2019 年。使用 Cox 比例风险模型估计结直肠癌的边缘 HR 和 95%CI。使用按日历时间特定倾向评分标准化死亡率权重对模型进行加权。预设的次要分析评估了与累积持续时间、累积剂量和治疗开始后时间的相关性。计算了五年和十年随访的伤害人数。
队列分别纳入了 1293749 例和 292387 例 PPI 和 H2RA 的使用者，中位随访时间为 4.9 年。虽然 PPI 的使用与结直肠癌的总体风险增加无关（HR：1.02，95%CI 0.92 至 1.14），但 HR 随着 PPI 使用的累积持续时间增加而增加（<2 年，HR：0.93，95%CI 0.83 至 1.04；2-4 年，HR：1.45，95%CI 1.28 至 1.60；≥4 年，HR：1.60，95%CI 1.42 至 1.80）。累积剂量和治疗开始后时间也存在类似的模式。五年和十年随访的伤害人数分别为 5343 人和 792 人。
与 H2RA 相比，任何 PPI 的使用均与结直肠癌风险增加无关，但长期使用可能与这种恶性肿瘤的风险适度增加相关。
