Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.
Health Research Institute, University of Canberra, Canberra, Australian Capital Territory, Australia.
Int J Colorectal Dis. 2021 Dec;36(12):2577-2584. doi: 10.1007/s00384-021-04022-5. Epub 2021 Sep 10.
Experimental evidence has revealed that phosphodiesterase five inhibitors (PDE5is) increase epithelial barrier function and suppress intestinal carcinogenesis. Few epidemiological studies have investigated the role of PDE5i in increasing the risk of colorectal cancer (CRC); however, these studies have proffered varying conclusions. We therefore aimed to perform a comprehensive review and meta-analysis to investigate whether PDE5i use is associated with the incidence of CRC.
Databases, namely, PubMed, Scopus, Embase, and Web of Science, were used for literature search. Observational studies (published until January 31, 2021) that assessed the association of PDE5i use with CRC incidence were considered. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model.
We identified four retrospective studies that involved 965,044 participants and 3,518 CRC cases detected during a mean follow-up of 12.7 years. Pooled results indicated a significantly reduced CRC risk among all PDE5i users (RR, 0.85; 95% CI, 0.76-0.95; P = 0.004, I = 63%). Moreover, continuous use of PDE5i was associated with a significantly reduced risk of CRC (RR, 0.63; 95% CI, 0.59-0.68; P < 0.001, I = 0.0%). However, the type of PDE5i exhibited no association with the risk of CRC (RR, 1.00; 95% CI, 0.98-1.02; I = 84.7%).
Our findings suggest that continuous use of PDE5i was associated with a significantly reduced risk of CRC development. Future studies with a longitudinal design and adequate control of confounding factors are required to clarify whether a longer duration of PDE5i use alters the risk of CRC.
实验证据表明，磷酸二酯酶 5 抑制剂（PDE5i）可增加上皮屏障功能并抑制肠道癌发生。少数流行病学研究调查了 PDE5i 在增加结直肠癌（CRC）风险中的作用，但这些研究得出的结论不一。因此，我们旨在进行全面的综述和荟萃分析，以调查 PDE5i 使用是否与 CRC 的发生有关。
使用数据库，即 PubMed、Scopus、Embase 和 Web of Science，进行文献检索。评估 PDE5i 使用与 CRC 发生率相关性的观察性研究（截至 2021 年 1 月 31 日发表）被纳入考虑。使用 DerSimonian-Laird 随机效应模型计算汇总相对风险（RR）估计值及其相应的 95%置信区间（CI）。
我们确定了四项回顾性研究，共涉及 965044 名参与者和 3518 例在平均 12.7 年随访期间检测到的 CRC 病例。汇总结果表明，所有 PDE5i 使用者的 CRC 风险显著降低（RR，0.85；95%CI，0.76-0.95；P=0.004，I=63%）。此外，连续使用 PDE5i 与 CRC 风险显著降低相关（RR，0.63；95%CI，0.59-0.68；P<0.001，I=0.0%）。然而，PDE5i 的类型与 CRC 风险无关（RR，1.00；95%CI，0.98-1.02；I=84.7%）。
我们的研究结果表明，连续使用 PDE5i 与 CRC 发生风险显著降低有关。需要进行具有纵向设计和充分控制混杂因素的未来研究，以阐明 PDE5i 使用时间的延长是否会改变 CRC 的风险。
