Pioglitazone and the Risk of Bladder Cancer: A Meta-Analysis.
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ABSTRACT: Funding
Tchaikapharma High Quality Medicines Inc.
SUBMITTER: Filipova E
PROVIDER: S-EPMC5544610 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta-analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose-response relationship with a generalized least-squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever-users of pioglitazone versus never-users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time- (P = 0.003) and dose-dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose- and time-dependent manner. Patients with long-term and high-dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.
| S-EPMC5911601 | biostudies-literature
Project description:Pioglitazone has been reported to increase the risk of bladder cancer but the conclusions of published clinical studies are confusing. We conducted a systematic review and meta-analysis of all eligible randomized controlled trial (RCT) studies and observational studies, in order to identify a more precise relationship between pioglitazone and risk of bladder cancer. We searched for publications up to January 24, 2018, in PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles and relevant reviews were also checked. Relative risk and 95% confidence interval (CI) were used to assess this correlation. A dose-related meta-analysis was performed as well. Data on RCT studies showed a null association between pioglitazone and bladder cancer. The pooled RR estimates of the 12 included studies illustrated that pioglitazone is associated with a 14% increased risk of bladder cancer (95% CI 1.03-1.26). No evidence of publication bias was detected. In the dose effect analysis, patients who used a higher dose of pioglitazone had an increased risk of bladder cancer. In conclusion, this meta-analysis indicated that pioglitazone is associated with an increased risk of bladder cancer. Further research should be conducted to confirm our findings and reveal the potential biological mechanisms.
| S-EPMC6021001 | biostudies-literature
Project description:BackgroundStudies investigating bladder cancer risk in pioglitazone-treated type 2 diabetes mellitus patients report conflicting results. Previous meta-analyses on this topic utilized publications prior to 2013. More long-term observational studies have been published since then. We reviewed the accumulated evidence and updated findings from previous meta-analyses.MethodsThis meta-analysis was based on a systematic review of peer-reviewed observational studies published prior to September 30, 2016. Eligible studies were identified using a specified MEDLINE search. References from included studies and from previous meta-analyses were screened for additional records. Meta-analysis hazards ratios were derived using a random-effects model. Several sensitivity analyses including hierarchical Bayesian meta-analysis with country-specific effects were conducted.ResultsOf 363 identified records, 23 studies were included in this review and 18 in the actual meta-analyses. For bladder cancer outcome, the estimated effect size for ever vs. never use of pioglitazone was 1.16 [95% confidence interval (CI), 1.04-1.28]. In the cumulative dose and duration analyses, highest effect was observed in the highest/longest exposure group, but substantial heterogeneity was present. In the sensitivity analysis, only studies adjusted for lifestyle-related factors were included and the frequentist effect size was 1.18 (95% CI, 1.00-1.40, p = 0.054). However, the risk was not verified in the Bayesian framework with an effect size of 1.17 [95% credible interval (CrI), 0.94-1.54].ConclusionsIn line with previous meta-analyses, we observed a small but statistically significant association between ever (vs. never) use of pioglitazone and bladder cancer risk; however, causality is not established and alternative explanations cannot be ruled out.
| S-EPMC6357234 | biostudies-literature
Project description:ObjectiveTo determine whether pioglitazone compared with other antidiabetic drugs is associated with an increased risk of bladder cancer in people with type 2 diabetes.DesignPopulation based cohort study.SettingGeneral practices contributing data to the United Kingdom Clinical Practice Research Datalink.ParticipantsA cohort of 145,806 patients newly treated with antidiabetic drugs between 1 January 2000 and 31 July 2013, with follow-up until 31 July 2014.Main outcome measuresThe use of pioglitazone was treated as a time varying variable, with use lagged by one year for latency purposes. Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident bladder cancer associated with pioglitazone overall and by both cumulative duration of use and cumulative dose. Similar analyses were conducted for rosiglitazone, a thiazolidinedione not previously associated with an increased risk of bladder cancer.ResultsThe cohort generated 689,616 person years of follow-up, during which 622 patients were newly diagnosed as having bladder cancer (crude incidence 90.2 per 100,000 person years). Compared with other antidiabetic drugs, pioglitazone was associated with an increased risk of bladder cancer (121.0 v 88.9 per 100,000 person years; hazard ratio 1.63, 95% confidence interval 1.22 to 2.19). Conversely, rosiglitazone was not associated with an increased risk of bladder cancer (86.2 v 88.9 per 100,000 person years; 1.10, 0.83 to 1.47). Duration-response and dose-response relations were observed for pioglitazone but not for rosiglitazone.ConclusionThe results of this large population based study indicate that pioglitazone is associated with an increased risk of bladder cancer. The absence of an association with rosiglitazone suggests that the increased risk is drug specific and not a class effect.
| S-EPMC4816602 | biostudies-literature
Project description:BackgroundSelenium is considered to be an antioxidant, and its high levels have been inversely associated with cancer risk of several sites. This meta-analysis examined the relationship between levels of selenium measured in serum and toenails, and the risk of bladder cancer.MethodsA meta-analysis using data from seven published epidemiologic studies (three case-control, three nested case-control, one case-cohort) published before March 2010 was done to examine the association between levels of selenium and bladder cancer. Fixed and random effects analyses were done to calculate meta-odds ratio (mOR) and 95% confidence intervals (CI). Heterogeneity among studies was measured by the I(2) statistic.ResultsOverall, the risk of bladder cancer was inversely associated with elevated levels of selenium according to a random-effects model (mOR = 0.61; 95% CI, 0.42-0.87). The mORs were 0.95 (95% CI, 0.69-1.27) and 0.55 (95% CI, 0.32-0.95) among men and women, respectively. Sex, type of sample specimen, smoking status, and study design were found to be potential sources of heterogeneity.ConclusionsA significant protective effect of selenium, observed mainly among women, may result from gender-specific differences in its accumulation and excretion. The heterogeneity found among studies was mainly linked to the different biological sample specimens used to measure the selenium concentrations and the small size of the studies. Although these results suggest a protective effect of selenium for bladder cancer risk, additional large studies are warranted to support these preliminary evidence.ImpactThe present results suggest a beneficial effect of high selenium intake for bladder cancer risk.
| S-EPMC6982398 | biostudies-literature
Project description:BACKGROUND: Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models. RESULTS: A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08-1.54), with significant evidence of heterogeneity among these studies (p<0.001, I(2) = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05-1.77) for diabetic men and 1.28 (0.75-2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14-1.55), with evident heterogeneity between studies (p = 0.002, I(2) = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30-1.82) and women (RR 1.50, 95% CI: 1.05-2.14). CONCLUSION: These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.
| S-EPMC3577653 | biostudies-other
Project description:To determine whether thiazolidinedione use is associated with a risk of bladder cancer.We searched MEDLINE and EMBASE in June 2012 (with PubMed update to July 2013) and conducted meta-analysis on the overall risks of bladder cancer with pioglitazone or rosiglitazone and the risk with different categories of cumulative dose or duration of drug use.We screened 230 citations and included 18 studies, comprising five randomized controlled trials (RCTs) and 13 observational studies. Meta-analysis showed a significantly higher overall risk of bladder cancer with pioglitazone in RCTs [7878 participants; odds ratio (OR) 2.51, 95% confidence interval (CI) 1.09-5.80] and observational studies (>2.6 million patients; OR for 'ever' users vs. non-users 1.21, 95% CI 1.09-1.35). Subgroup analysis of observational studies by cumulative dose showed the risk of bladder cancer to be greatest with >28.0?g of pioglitazone (OR 1.64, 95% CI 1.28-2.12). A significantly increased risk was found with both 12-24 months (OR 1.41, 95% CI 1.16-1.71) and >24 months (OR 1.51, 95% CI 1.26-1.81) cumulative durations of pioglitazone exposure. No significant risk was seen with rosiglitazone in RCTs (OR 0.84, 95% CI 0.35-2.04) or 'ever' users vs. non-users in observational studies (OR 1.03, 95% CI 0.94-1.12); the evidence for any relationship between bladder cancer risk and rosiglitazone cumulative duration is limited and inconsistent. Direct comparison of pioglitazone to rosiglitazone 'ever' users yielded an OR of 1.25 (95% CI 0.91-1.72).A modest but clinically significant increase in the risk of bladder cancer with pioglitazone was found, which appears to be related to cumulative dose and duration of exposure. We recommend that prescribers limit pioglitazone use to shorter durations.
| S-EPMC4137819 | biostudies-other
Project description:To clarify the inconsistent reports of bladder cancer risk in foundry workers, a meta-analytic review of epidemiological studies was undertaken. Summary risk estimates (SRE) were calculated from 40 systematically extracted results. Weakly increased risks were observed overall, with an SRE of 1.11. Twenty three selected study results with better exposure information yielded an SRE of 1.16. This weak increase in risk is consistent with estimates obtained from dose-response trends of PAH exposures in aluminium smelter workers. Summary estimates did not vary substantially with exposure quality, study design, control for smoking, or when limiting the meta-analysis to large study results. Exposure-response findings showed significantly increased risks of about 1.6 to 1.7 after 20 or more years of employment, but this was based on few studies. Occupation specific SREs showed a 40-50% increased risk among moulders, casters, and unskilled foundry labourers. There was limited evidence that bladder cancer risk correlated with lung cancer risk, which is a more established risk among foundry workers. The small increased risk observed is prone to bias and confounding. Further studies of dose-response trends would greatly aid in determining whether this observed association is causal.
| S-EPMC1740225 | biostudies-literature
Project description:BackgroundDespite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) infection and risk of bladder cancer, the studies remain inconclusive.MethodsThe prevalence of HPV in bladder cancer was estimated by pooling data from 52 studies, taking into consideration the heterogeneity from major related parameters including study region, histological type, HPV DNA specimen, publication calendar period, and detection method. Moreover, the association of HPV infection with bladder cancer was tested by a meta-analysis with 19 case-control studies.ResultsAn HPV prevalence of 16.88% (95% confidence interval [CI], 15.53%-18.31%) among the bladder cancer cases was revealed, most of whom were high-risk HPV types (15.82% [95% CI, 14.37%-17.36%]). The prevalence varied by region, types of HPV DNA specimen, and polymerase chain reaction primers used. A significantly increased risk of bladder cancer was shown for the positivity of overall HPV (odds ratio, 2.84 [95% CI, 1.39-5.80]), which was also infuenced by HPV type, study region, HPV DNA specimen, and detection method.ConclusionsInfection of high-risk HPV types, especially HPV16, may play a role in bladder carcinogenesis.
| S-EPMC3114469 | biostudies-literature
Project description:Meta-analysis of genome-wide association studies of bladder cancer risk
| PRJNA993798 | ENA