Potential Gene Association Studies of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.
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ABSTRACT:
SUBMITTER: Yang X
PROVIDER: S-EPMC8213036 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Anthracyclines play an important role in the management of patients with cancer but the development of anthracycline-induced cardiotoxicity (ACT) remains a significant concern for most clinicians. Recently, genetic approach has been used to identify patients at increased risk of ACT. This systematic review assessed the association between genomic markers and ACT. A systematic literature search was performed in Medline, PubMed, Cochrane Central Register of Controlled Studies, CINAHL Plus, AMED, EMBASE and HuGE Navigator from inception until May 2016. Twenty-eight studies examining the association of genetic variants and ACT were identified. These studies examined 84 different genes and 147 single nucleotide polymorphisms. Meta-analyses showed 3 risk variants significantly increased the risk for ACT; namely ABCC2 rs8187710 (pooled odds ratio: 2.20; 95% CI: 1.36-3.54), CYBA rs4673 (1.55; 1.05-2.30) and RAC2 rs13058338 (1.79; 1.27-2.52). The current evidence remains unclear on the potential role of pharmacogenomic screening prior to anthracycline therapy. Further research is needed to improve the diagnostic and prognostic role in predicting ACT.
| S-EPMC5428315 | biostudies-literature
Project description:Aims Although chemotherapy agents are used to treating cancers, they have serious side effects, like their harmful effects on the cardiovascular system, limiting the clinical use of these chemotherapy agents. This study aimed to systematically investigate the potential role of ginseng derivatives in the prevention of chemotherapy-induced cardiac toxicity. Methods This systematic review was performed according to PRISMA guidelines strategy in databases till August 2022. First, identify studies related to using search terms in titles and abstracts. After studying and screening 209 articles, 16 articles were selected in this study according to our inclusion and exclusion criteria. Results According to the findings of this study, ginseng derivatives showed significant changes in biochemical, histological, and heart weight loss, as well as a reduction in mortality, which occurred in the groups treated with chemotherapy agents compared to the control groups. Co-administration of ginseng derivatives with chemotherapy agents inhibited or reversed these changes to near-moderate levels. The protective effects of ginseng derivatives can be due to their anti-inflammatory, anti-oxidant, and anti-apoptotic action. Conclusion This systematic review shows evidence that concomitant administration of ginseng derivatives improves chemotherapy-induced cardiac toxicity. However, for better conclusions about the practical mechanisms of ginseng derivatives in reducing the cardiac toxic effects of chemotherapy agents and evaluating the efficacy and safety of the compound simultaneously, it is necessary to design comprehensive studies.
| S-EPMC9946988 | biostudies-literature
Project description:Some randomized controlled trials (RCTs) have tested the efficacy of beta-blockers as prophylactic agents on cancer therapy-induced cardiotoxicity; however, the quality of this evidence remains undetermined. This systematic review and meta-analysis study aims to evaluate the prophylactic effects of beta-blockers, especially carvedilol, on chemotherapy-induced cardiotoxicity. RCTs were identified by searching the MEDLINE (PubMed), Embase (OvidSP), Cochrane CENTRAL (OvidSP), etc., until December 2017. Inclusion criteria were randomized clinical trial and adult cancer patients started beta-blockers before chemotherapy. We evaluated the mean differences (MD) by fixed- or random-effects model and the odds ratio by Peto's method. Primary outcome was the left ventricular ejection fraction (LVEF) of patients after chemotherapy, and secondary outcomes were all-cause mortality, clinically overt cardiotoxicity, and other echocardiographic measurements. In total, we included six RCTs that used carvedilol as a prophylactic agent in patients receiving chemotherapy. The LVEF was not significantly distinct between those using carvedilol and placebo after chemotherapy (MD, 1.74; 95% confidence interval (CI), - 0.18 to 3.66; P = 0.08). The incidence of clinically overt cardiotoxicity was lower in the carvedilol group compared with the control group (Peto OR, 0.42; 95% CI, 0.20-0.89; P = 0.02). Furthermore, after chemotherapy, the LV end-diastolic diameter did not increase in the carvedilol group compared with the placebo group (MD, - 1.41; 95% CI, - 2.32 to - 0.50; P = 0.002). The prophylactic use of carvedilol exerted no impact on the early asymptomatic LVEF decrease but seemed to attenuate the frequency of clinically overt cardiotoxicity and prevent ventricular remodeling.
| S-EPMC6476829 | biostudies-literature
Project description:Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.
| S-EPMC8649276 | biostudies-literature
Project description:BackgroundBenign prostate hyperplasia (BPH) is the most common urological problem in elderly males. Recent studies have reported polymorphism in various metabolic genes in BPH. However, their association with the susceptibility of BPH is still inconsistent. Here, we systematically reviewed and performed a meta-analysis of CYP17, VDR, and ACE genes to determine their precise association with the risk of BPH.MethodsA comprehensive literature search for published studies on candidate gene associations involving vitamin D receptor (VDR), angiotensin-converting enzyme (ACE), and CYP17 genes with the risk of BPH was done up to April 2020 in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. Fixed/random effects models were used to estimate the odd's ratio (OR) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias.ResultsWe found a total of 23 studies containing 3461 cases and 3833 controls for these gene polymorphisms. A significant association of ACE gene polymorphism was observed under the recessive (II vs. ID + DD) model for BPH susceptibility compared to control subjects (overall OR = 1.67, 95% CI = 1.03-2.73). Similar trends were observed for ACE gene polymorphism in Caucasian (OR = 6.18, 95% CI = 1.38-27.68) and Asian (OR = 1.42, 95% CI = 0.99-2.03) populations under study. No significant association was observed in VDR and CYP17 gene polymorphisms in any dominant or recessive models.ConclusionSignificant OR demonstrated the implication of ACE gene polymorphism in the proliferation of prostate tissue, which in turn is associated with BPH susceptibility. However, prospective studies at large scale and sample size are needed to confirm the current findings.
| S-EPMC8985373 | biostudies-literature
Project description:Importance:Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy-related cardiac dysfunction (CTRCD) has not been performed, to our knowledge. Objective:To explore the prognostic value of GLS for the prediction of CTRCD. Data Sources:Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018. Study Selection:Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD. Data Extraction and Synthesis:Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Main Outcomes and Measures:The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms. Results:Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from -21.0% to -13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27; 95% CI, 7.73-19.47; area under the HSROC, 0.86; 95% CI, 0.83-0.89). For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82; 95% CI, 5.84-42.85; area under the HSROC, 0.86; 95% CI, 0.83-0.89). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity. Conclusions and Relevance:In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.
| S-EPMC6705141 | biostudies-literature
Project description:Purpose of reviewThe goal of this review is to summarize current understanding of pharmacogenetics and pharmacogenomics in chemotherapy-induced cardiotoxicity.Recent findingsMost of the studies rely on in vitro cytotoxic assays. There have been several smaller scale candidate gene approaches and a handful of genome-wide studies linking genetic variation to susceptibility to chemotherapy-induced cardiotoxicity. Currently, pharmacogenomic testing of all childhood cancer patients with an indication for doxorubicin or daunorubicin therapy for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is recommended. There is no recommendation regarding testing in adults. There is clear evidence pointing to the role of pharmacogenetics and pharmacogenomics in cardiotoxicity susceptibility to chemotherapeutic agents. Larger scale studies are needed to further identify susceptibility markers and to develop pharmacogenomics-based risk profiling to improve quality of life and life expectancy in cancer survivors.
| S-EPMC6371783 | biostudies-literature
Project description:Genetic susceptibility to methamphetamine use disorder is poorly understood. No twin or adequately powered genome-wide association studies (GWASs) have been conducted. However, there are a large number of hypothesis-driven candidate gene association studies, which were systematically reviewed herein. Seventy-six studies were identified, investigating markers of 75 different genes. Allele frequencies, odds ratios, 95 % confidence intervals and power were calculated. Risk of bias was also assessed as a quality measure. Meta-analyses were conducted for gene markers if three or more studies were available. Eleven markers from adequately powered studies were significantly associated with methamphetamine use disorder, with Fatty Acid Amide Hydrolase (FAAH) and Brain Derived Neurotrophic Factor (BDNF) representing promising targets. Limitations of these studies include unclear rationale for candidate gene selection, low power and high risk of bias. Future research should include replications to enable more meta-analyses, well-powered GWASs or whole exome or genome sequencing, as well as twin and family studies to further complement the findings of this review to uncover genetic contributions toward methamphetamine use disorder.
| S-EPMC7856253 | biostudies-literature
Project description:To evaluate the contribution of association studies of candidate polymorphisms to inherited predisposition to Hodgkin lymphoma (HL), we conducted a systematic review and meta-analysis of published case-control studies. Of the variants examined more than once in candidate gene association studies, we identified 21 studies that reported on 12 polymorphic variants in 10 genes. Data were also extracted from a published genome wide association study to allow analysis of an additional 47 variants in a further 30 genes. Promising associations were seen in nine of the variants (p < 0.05). Given that the estimated false positive report probabilities (FPRPs) for all associations are high (i.e. FPRP > 0.2), these findings should be interpreted with caution. While studies of candidate polymorphisms may be an attractive means of identifying risk factors for HL, future studies should employ sample sizes adequately powered to identify variants having only modest effects on HL risk. Furthermore, because of aetiological heterogeneity within HL, stratification of genotyping according to age, tumour Epstein-Barr virus status and histology is essential. Copyright © 2015 John Wiley & Sons, Ltd.
| S-EPMC6175040 | biostudies-literature
Project description:Background Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact of chemotherapeutic agents on the integrity and function of the right ventricle (RV). Objectives The current metanalysis compared pre- chemotherapy versus post- chemotherapy RV parameters measured on 2D echocardiography in patients receiving anthracycline and/or trastuzumab across all breast cancer patients. Methods A systematic search across PubMed, EMBASE and Cochrane databases were performed from inception of the databases until November 2021 for relevant studies. We used the inverse variance method with a random effect model and DerSimonian and Laird method of Tau2 generation to calculate mean difference [MD] with 95% confidence interval [CI]. The analysis was carried out using RevMan Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Results Fifteen studies, constituting total of 644 patients, met the inclusion criteria, with most studies having a follow up period of less than 12 months from initiation of chemotherapy. Anthracycline and/or Trastuzumab chemotherapy resulted in a statistically significant reduction in right ventricular ejection fraction (RVEF) at follow-up [MD: 2.70, 95% CI: 0.27 to 5.13, P-value- 0.03, I2- 71%, χ2P-value < 0.05]. Treatment with Anthracycline and/or Trastuzumab chemotherapy resulted in a significant reduction in RV fractional area change (RVFAC) at follow-up [MD: 3.74, 95% CI: 1.33 to 6.15, P-value < 0.01, I2- 68%, χ2P-value < 0.05]. RV free wall longitudinal strain (RVFWLS) was lower at baseline, while LVEF was significantly reduced at follow-up [MD: -1.00, 95% CI: -1.86 to -0.15, P-value < 0.05, I2- 0%, χ2P-value-0.40], [MD: 4.04, 95% CI: 2.08 to 6.01, P-value < 0.01, I2- 91%, χ2P-value < 0.05], respectively. However, treatment with Anthracycline and/or Trastuzumab chemotherapy had no statistically significant effect on Tricuspid annular plane systolic excursion (TAPSE) at follow-up [MD: 0.53, 95% CI: -0.11 to 1.17, P-value-0.11, I2- 98%, χ2P-value < 0.05]. Conclusions Chemotherapy with anthracyclines and trastuzumab negatively affects right ventricular function leading to decline in RVEF, RVFAC, RVFWLS and LVEF.
| S-EPMC10434797 | biostudies-literature