Phosphodiesterase type 5 inhibitors use and risk of colorectal cancer: a systematic review and meta-analysis

Bhagavathula, Akshaya Srikanth; Tesfaye, Wubshet; Vidyasagar, Kota

doi:10.1007/s00384-021-04022-5

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…Pooled results from this meta-analysis of six studies suggest that PDE5 inhibitors have a protective role in preventing CRC and advanced colorectal polyps. These findings concur with those of a previously published meta-analysis of four studies examining the relationship between PDE5 inhibitor use and CRC incidence [37].…”

Section: Discussionsupporting

confidence: 92%

“…These findings concur with those of a previously published meta‐analysis of four studies examining the relationship between PDE5 inhibitor use and CRC incidence [37]. Bhagavathula et al [37] reported that users of PDE5 inhibitors had a significantly reduced risk of developing CRC (RR 0.85, CI 0.76–0.95, p = 0.004). However, omission of two relevant studies [22, 29], exclusion of subgroup analysis on primary and secondary prevention and lack of prospective PROSPERO registration of the previous meta‐analysis warranted the conduction of a more comprehensive review on this subject area.…”

Section: Discussionsupporting

confidence: 89%

“…Bhagavathula et al [37] reported that users of PDE5 inhibitors had a significantly reduced risk of developing CRC (RR 0.85, CI 0.76-0.95, p = 0.004). However, omission of two relevant studies [22,29],…”

Section: Discussionmentioning

confidence: 99%

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The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta‐analysis

Cullinane,

Brett,

Devane

et al. 2023

Colorectal Disease

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AimInflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti‐inflammatory properties, phosphodiesterase‐5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta‐analysis of published peer‐reviewed studies whether an association exists between PDE5i use and CRC risk.MethodThis study was guided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i ‘ever‐users’ and PDE5i ‘never‐users’. Meta‐analysis was performed using RevMan version 5.ResultsFour observational cohort studies and two case–control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever‐users. Patients who were PDE5i ever‐users had a significantly lower incidence of CRC or advanced colorectal polyps than never‐users (OR 0.88, CI 0.79–0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75–0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never‐users.ConclusionOur study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

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The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta‐analysis

Cullinane,

Brett,

Devane

et al. 2023

Colorectal Disease

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“…Besides, it is no efficient in controlling parameters other than hemodynamic system (HbA1c, endothelin 1 serum level, high sensitivity C-reactive protein plasma level and interleukin six serum level) in type II diabetes patients ( Santi et al, 2015 ; Poolsup et al, 2016 ). Lastly, according to the pooled results of a meta-analysis, sildenafil did not lower the risk of colorectal cancer based on results of amount of population based studies ( Bhagavathula et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Function of sildenafil on diseases other than urogenital system: An umbrella review

Chen

Huang²,

Cao³

et al. 2023

Front. Pharmacol.

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Background: To investigate the function of sildenafil on diseases other than urogenital system, an umbrella review was conducted.Methods: Meta-analysis and systematic reviews on this topic were comprehensively evaluated in this umbrella review. Quality of evidence was evaluated through AMSTAR and the Grading of Recommendations, Assessment, Development and Evaluation system to generate a reliable and valid conclusion.Results: 77 out of 1164 meta-analysis were enrolled. 33 significant outcomes and 41 non-significant outcomes were extracted from all eligible articles. We found sildenafil did significant help in reducing arterial systolic pressure, mean pulmonary arterial pressure, pulmonary arterial pressure, systolic pulmonary arterial pressure in patients with pulmonary and cardiovascular diseases. Besides, sildenafil also improved exercise capacity or performance in patients with pulmonary and cardiovascular diseases. Other than these patients, this drug contributed great help in pregnant women with fetal growth restriction and preeclampsia by increasing the weight of newborns and lowering uterine and umbilical pulsatility indices. Additionally, it was reported that utilization of sildenafil has brought increased risk of melanoma.Conclusion: We can conclude from our study that sildenafil played an important role in many fields, especially in vascular protection. This finding provides a strong evidence for further expansion of sildenafil utilization in other diseases.

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How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme

et al. 2022

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Phosphodiesterase type 5 inhibitors use and risk of colorectal cancer: a systematic review and meta-analysis

Cited by 4 publications

References 19 publications

The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta‐analysis

The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta‐analysis

Function of sildenafil on diseases other than urogenital system: An umbrella review

How do phosphodiesterase-5 inhibitors affect cancer? A focus on glioblastoma multiforme

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