Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma.
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ABSTRACT:
SUBMITTER: Loeb S
PROVIDER: S-EPMC5437700 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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
Project description:Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up to February 2017, and a random effects model was used to calculate the summary risk estimates. Five observational studies were included. Five studies reports encompassed a total of 15,979 melanoma cases occurring among 1, 188,414 participants. The pooled multivariable-adjusted RR of melanoma in patients with using PDE5 inhibitors was 1.12 (95% CI: 1.03-1.21, I2 = 0.48). Findings from this systematic review support that PDE5 inhibitor use is associated with increased risk of melanoma in ED patients, the result remains inclusive and warrants further study in the future.
| S-EPMC5542281 | biostudies-other
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.
| S-EPMC5046205 | biostudies-literature
Project description:Background and purposeData on the association between PDE4D SNP 87 and the risk of ischemic stroke are contentious and debatable. The present meta-analysis was undertaken to systematically summarize the possible association.MethodsBased on comprehensive search of PubMed, Embase, and CNKI databases, we identified 18 eligible articles examining the relationship between PDE4D SNP 87 and ischemic stroke risk. We evaluated the strength of relationship using odds ratios (ORs) with 95% confidence intervals (CIs).ResultsIn the overall analysis, PDE4D SNP 87 was not found to have effects on the risk of ischemic stroke. The null association persisted in the subgroup analyses according to ethnicity and sample size.ConclusionsOur meta-analysis suggests that PDE4D SNP 87 may not represent an independent risk factor for ischemic stroke development.
| S-EPMC4402747 | biostudies-literature
Project description:This meta-analysis was conducted to determine the potential association between adiposity and glaucoma incidence.A comprehensive literature search was performed in PubMed and ISI Web of Science. A meta-analysis was conducted using STATA software.Fifteen eligible studies involving 2,445,980 individuals were included to investigate the association between adiposity and glaucoma incidence. The relative risks (RRs) were pooled with 95% confidence intervals (CI) by using a random-effects model. The pooled RR between adiposity and elevated intraocular pressure (IOP) was 1.73 (95% CI, 1.18-2.54), whereas that between adiposity and open-angle glaucoma (OAG) was 0.97 (95% CI, 0.83-1.13). The pooled RR between abdominal adiposity and glaucoma was 1.28 (95% CI, 1.15-1.41), whereas that between general adiposity and glaucoma was 1.09 (95% CI, 0.87-1.37). Results of subgroup analysis by sex indicated the association between adiposity and glaucoma in the female group (RR, 1.31; 95% CI, 1.05-1.64), but not in the male group (RR, 1.11; 95% CI, 0.77-1.60). The pooled RR of cohort studies and cross-sectional studies were 1.00 (95% CI, 0.84-1.20) and 1.22 (95% CI, 0.89-1.66), respectively.Adiposity has a higher risk of elevated IOP, and abdominal adiposity has a positive association with glaucoma, especially in female patients.
| S-EPMC5485359 | biostudies-other
Project description:Phosphodiesterase type 5 inhibitors (PDE5-Is) are first-line drugs for erectile dysfunction. Non-arteritic anterior ischemic optic neuropathy (NAION) has been linked with PDE5-I use. However, no meta-analysis or conclusive review has explored the association between NAION and PDE5-I use.To investigate the association between PDE5-I use and risk of NAION.A comprehensive literature search was conducted using online databases in October 2017 to obtain studies researching the association between PDE5-I application and occurrence of NAION. Summarized unadjusted risk ratios (RRs) with 95% CIs were calculated for the strength of this association. This study was conducted in accordance to Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and registered in PROSPERO under number CRD42017080865.The strength of association between PDE5-I use and risk of NAION was assessed through pooled unadjusted RRs and 95% CIs.5 original articles with 6 clinical observations were included in the meta-analysis. No significant higher risk of NAION was observed after the use of PDE5-Is within a 1-month period (RR = 1.16, 95% CI = 0.98-1.39, P = .09). Subgroup analyses indicated 2 PDE5-Is were significantly related to NAION (tadalafil: RR = 2.14, 95% CI = 1.20-3.84, P = .01; sildenafil: RR = 2.25, 95% CI = 1.29-3.94, P = .004).Although we found no association between NAION and PDE5-I use, our results should be interpreted cautiously because we included only observational studies and could not control for potential confounders. Because NAION is a rare ocular disease and difficult to diagnose, this association should be confirmed in prospective comparative studies with larger samples and more rigorous designs. Liu B, Zhu L, Zhong J, et al. The Association Between Phosphodiesterase Type 5 Inhibitor Use and Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis. Sex Med 2018;6:185-192.
| S-EPMC6085407 | biostudies-other
Project description:IntroductionThe use of proton-pump inhibitors (PPI) may be associated with an increased risk of gastric cancer (GC).ObjectiveTo review and meta-analyse available literature investigating the association between PPI use and GC risk.MethodsTwo independent reviewers systematically searched Ovid MEDLINE, EMBASE, and Cochrane Library (inception to July 2020) for case-control and cohort studies assessing the association between PPI use and GC according to a predefined protocol in PROSPERO (CRD42018102536). Reviewers independently assessed study quality, extracted data, and meta-analysed available and newly calculated odds ratios (ORs) using a random-effects model, and stratified for GC site (cardia versus non-cardia) and PPI duration (<1 year, 1-3 years, >3 years).ResultsWe screened 2,396 records and included five retrospective cohort and eight case-control studies comprising 1,662,881 individuals in our meta-analysis. In random-effect models, we found an increased GC risk in PPI users [OR: 1.94, 95% confidence interval (95% CI): 1.47-2.56] with high statistical heterogeneity (I 2 = 82%) and overall moderate risk of bias. Stratified analyses indicated a significant risk increase in non-cardia (OR: 2.20, 95% CI: 1.44-3.36, I 2 = 77%) with a similar non-significant trend in cardia regions (OR: 1.77, 95% CI: 0.72-4.36, I 2 = 66%). There was no GC increase with longer durations of PPI exposure (<1 year: OR: 2.29, 95% CI: 2.13-2.47, I 2 = 0%; 1-3 years: OR: 1.46, 95% CI: 0.53-4.01, I 2 = 35%; >3 years: OR: 2.08, 95% CI: 0.56-7.77, I 2 = 61%).ConclusionWe found a twofold increased GC risk among PPI users, but this association does not confirm causation and studies are highly heterogeneous. PPI should only be prescribed when strictly indicated.
| S-EPMC8586163 | biostudies-literature
Project description:C-reactive protein (CRP) has been indicated to be associated with the pathogenesis of schizophrenia (SZ) and other psychiatric disorders. The aim of this study is to investigate whether peripheral blood CRP levels are associated with the risk of SZ. We searched literature from databases of Pubmed, Embase and the Cochrane Library from inception to November 1, 2016 for studies that reported serum or plasma CRP levels in patients with SZ and non-SZ controls. At least two reviewers decided on eligibility and extracted data from included studies. Random effects meta-analyses were performed using standardized mean difference (SMD) as the effect estimate of the differences in CRP levels between subjects with SZ and healthy controls. We identified 18 studies representing 1963 patients with SZ and 3683 non-SZ controls. Compared with non-schizophrenics, blood CRP levels were moderately increased in people with SZ (SMD 0.53, 95% CI 0.30 to 0.76) irrespective of study region, sample size of included studies, patient mean age, age of SZ onset and patient body mass index. Publication bias was not detected through Egger's linear regression test (P = 0.292). We noticed that patients in Asia or Africa (n = 6, SMD 0.73, 95% CI 0.26 to 1.21) and whose age less than 30 years (n = 5, SMD 0.76, 95% CI 0.07 to 1.58) had substantially higher CRP levels. Our study provides evidence that higher CRP levels are associated with increased risk of SZ, especially for young adult patients less than 30 years. Further large-scale studies are strongly warranted to further confirm this association.
| S-EPMC5650435 | biostudies-other
Project description:Quantification of the association between the intake of cholesterol and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to summarize the evidence from epidemiological studies of cholesterol intake and the risk of pancreatic cancer. Pertinent studies were delivered by PubMed and Web of Knowledge issued through April of 2014. A random effects model was used to process the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. With 4513 pancreatic cases exemplified, 16 articles were applied in the meta-analysis. Pooled results suggest that cholesterol intake level was significantly associated with the risk of pancreatic cancer [summary relative risk (RR) = 1.371, 95%CI = 1.155-1.627, I(2) = 58.2%], especially in America [summary RR = 1.302, 95%CI = 1.090-1.556]. A linear dose-response relation was attested that the risk of pancreatic cancer rises by 8% with 100 mg/day of cholesterol intake. [summary RR = 1.08, 95% CI = 1.04-1.13]. In conclusion, our analysis suggests that a high intake of cholesterol might increase the risk of pancreatic cancer, especially in America.
| S-EPMC4316166 | biostudies-other
Project description:BACKGROUND:Murine double minute 2 homolog (MDM2) plays an important role in the downregulation of P53 tumor suppressor gene. MDM2 inhibits P53 transcriptional activity and thereby results in accelerated tumor formation. Overexpression of MDM2 has been found in several cancer types including endometrial cancer. SNP309 is located in the promoter region of MDM2 and contributes to the overexpression of MDM2. The association between MDM2 SNP309 polymorphism and endometrial cancer risk has been investigated in several studies; however, the conclusion remains controversial. OBJECTIVES:We performed the present meta-analysis to give a comprehensive conclusion of the association between MDM2 SNP309 polymorphism and endometrial cancer susceptibility. METHODS:We conducted a literature research on PubMed, Embase, Cochrane Library, OVID, Web of Science, Wan Fang, CNKI, and CQVIP databases up to July 31, 2018. Newcastle-Ottawa scale was used to assess the quality of studies. We evaluated the strength of association by combining odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models under a fixed-effect model or random-effect model. We further conducted subgroup analysis by ethnicity, source of control, histological type, clinical type, grade, and stage of tumor. Sensitivity analysis and publication bias were also performed. RESULTS:Nine eligible studies were finally included in our meta-analysis. We found MDM2 SNP309 polymorphism increased the risk of endometrial cancer under allele model (OR: 1.23, 95% CI: 1.06-1.41, P?=?.005), homozygote model (OR: 1.43, 95% CI: 1.13-1.81, P?=?.003) and recessive model (OR: 1.55, 95% CI: 1.17-2.04, P?=?.002). Subgroup analysis suggested a similar elevated risk in both Asians and Caucasians. We identified a strong association of enhanced susceptibility to endometrial cancer in endometrioid group (OR: 2.13, 95% CI: 1.28-3.54, P?=?.004) and Type I group (OR: 1.89, 95% CI: 1.25-2.86, P?=?.002) under dominant model. We identified no significant publication bias according to Egger's test. CONCLUSIONS:Our meta-analysis suggested that MDM2 SNP309 polymorphism increased the risk of endometrial cancer significantly, especially in endometrioid and Type I endometrial cancer, indicating MDM2 could serve as a potential diagnostic factor marker for endometrial cancer.
| S-EPMC6310604 | biostudies-other