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Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer.

ABSTRACT: Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. We aimed to explore whether post-diagnostic use of PDE5 inhibitors was associated with a better prognosis among male patients with colorectal cancer (CRC) and the role of open surgery in the association. Here we show that post-diagnostic use of PDE5 inhibitors is associated with a decreased risk of CRC-specific mortality (adjusted HR?=?0.82, 95%?CI 0.67-0.99) as well as a decreased risk of metastasis (adjusted HR?=?0.85, 95%?CI 0.74-0.98). Specifically, post-operative use of PDE5 inhibitors has a strong anti-cancer effect. The reduced risk of metastasis is mainly due to distant metastasis but not regional lymphatic metastasis. PDE5 inhibitors have the potential to be an adjuvant drug for patients with CRC to improve prognosis, especially those who have undergone open surgery.

SUBMITTER: Huang W

PROVIDER: S-EPMC7314744 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer.

Huang Wuqing W Sundquist Jan J Sundquist Kristina K Ji Jianguang J

Nature communications 20200624 1

Phosphodiesterase-5 (PDE5) inhibitors are suggested to have anti-tumor effects and to inhibit surgery-induced immunosuppression. We aimed to explore whether post-diagnostic use of PDE5 inhibitors was associated with a better prognosis among male patients with colorectal cancer (CRC) and the role of open surgery in the association. Here we show that post-diagnostic use of PDE5 inhibitors is associated with a decreased risk of CRC-specific mortality (adjusted HR = 0.82, 95% CI 0.67-0.99) as well a ...[more]

PMID: 32581298

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Phosphodiesterase 5 Inhibitor Use and Risk of Conventional and Serrated Precursors of Colorectal Cancer.

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| S-EPMC7867618 | biostudies-literature

Use of sildenafil or other phosphodiesterase inhibitors and risk of melanoma.

Project description:Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma.We conducted two parallel case-control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic health records. Identifying men with histologically verified melanoma (cases) matched on birth year to 10 cancer-free controls, we estimated odds ratios (OR) for melanoma associated with high use of PDEIs (?100 tablets filled), adjusting for available confounders.We identified 7045 DNHR and 2972 KPNC cases with invasive melanoma. The adjusted OR for invasive melanoma associated with high PDEI use was 1.22 (95% confidence interval (CI), 0.99-1.49) in DNHR and 0.95 (95% CI, 0.78-1.14) in KPNC. Odds ratios were highest for localised invasive melanoma in DNHR (OR, 1.21) and melanoma in situ in KPNC (OR, 1.15), and lowest for non-localised disease in both populations (ORs 0.75 and 0.61, respectively). The increased ORs were slightly attenuated upon adjustment for markers of health-care utilisation.We found little evidence for a causal association between PDEI use and risk of melanoma. The marginally increased risk of early stage disease likely resulted from more frequent health-care contacts among PDEI users.

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Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-12 | GSE81582 | GEO

Prediagnostic use of low-dose aspirin and risk of incident metastasis and all-cause mortality among patients with colorectal cancer.

Project description:AimsPrevious studies suggest that the use of low-dose aspirin before a colorectal cancer (CRC) diagnosis may be associated with a decreased risk of CRC progression. Data supporting this association, however, have been inconsistent. We evaluate whether the use of prediagnostic low-dose aspirin is associated with a lower risk of metastases and all-cause mortality in CRC patients.MethodsUsing a large Italian population-based primary care database, we identified a cohort of 7478 patients newly diagnosed with nonmetastatic CRC between 2000 and 2013. Use of prediagnostic low-dose aspirin was compared with no use of low-dose aspirin. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident metastasis and of all-cause mortality associated with prediagnostic low-dose aspirin use, both overall and by duration of use.ResultsThere were 314 incident metastatic events and 2189 deaths during a mean follow-up time of 4.4 and 4.7 years, respectively. Overall prediagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis (HR 0.88; 95% CI 0.63-1.22) or all-cause mortality (HR 1.09; 95% CI 0.96-1.22) in CRC patients. Cumulative duration of aspirin use was not associated with a decreased risk of incident metastasis (P-trend = .22) or all-cause mortality (P-trend = .38). These findings remained consistent in sensitivity analyses.ConclusionIn this real-world, population-based study, the prediagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis or all-cause mortality in CRC patients.

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Genomic characterization of liver metastases from colorectal cancer patients.

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Prognostic factors for ovarian metastases in colorectal cancer patients.

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Genomic characterization of liver metastases from colorectal cancer patients [PrimeView]

Project description:Metastatic dissemination is the most frequent cause of death sporadic colorectal cancer (sCRC) patients. The genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluate the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases while expressed at normal levels in their primary tumors, suggesting an increased genomic instability of neoplastic cells from metastatic versus primary tumor samples. Of note, once tumoral samples were normalized vs. non-tumoral colorectal tissue, only three mRNAS (i.e.: DEFB1, COL12A and PTGER3) and one miRNA (i.e.: miR-572) emerged as significantly deregulated in the liver metastases vs. the primary tumor. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlight the activation of genes associated with the TGFβ signaling pathway, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis.

2017-06-12 | GSE81558 | GEO

Liver metastases originating from 4 colorectal cancer patients (CRC-LM).

Project description:Using liver metastases from 4 colorectal cancer patients (CRC-LM), we explored one receptor: EGFR whose signaling triggers cell proliferation and is exacerbated in many tumors.

2023-06-14 | GSE217414 | GEO

Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies.

Project description:BackgroundPhosphodiesterase type 5 inhibitor (PE5i) administration may stimulate the proliferation and survival of melanocytes. However, discrepancies remain regarding the association between PDE5i use and melanoma risk in observational studies in humans.AimTo evaluate the association between PDE5i use and melanoma in a meta-analysis.Materials and methodsStudies were identified by searching the PubMed and Embase databases. A random-effects model was applied to synthesize the data. A stratified study was performed to evaluate the influence of study characteristics on outcomes.ResultsFour prospective cohort studies and three case-control studies with 1,534,615 male participants and 16,053 melanoma cases were incorporated. Patients who received a PDE5i had a significantly increased risk for melanoma (adjusted risk ratio [RR] =1.12, 95% CI =1.03-1.33, P=0.008) with moderate heterogeneity (I2=54%). Cohort studies (adjusted RR =1.22, 95% CI =1.02-1.46, P=0.03) largely contributed to this result rather than case-control studies. Subsequent stratified analyses revealed that sildenafil was associated with an increased risk of melanoma (adjusted RR =1.26, 95% CI =1.07-1.50, P=0.007), but tadalafil and vardenafil were not. Also, PDE5i use was associated with a significantly increased risk of in situ melanoma (adjusted RR =1.31, 95% CI =1.01-1.69, P=0.04), but not of localized or nonlocalized melanoma.ConclusionPDE5i use may be associated with a significantly increased risk for melanoma in men. However, further research is needed to determine whether the association is causative.

| S-EPMC5804137 | biostudies-literature

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