Abstract:We report a modifying effect of a polymorphism of CELF4 (rs1786814) on the dose-dependent association between anthracyclines and cardiomyopathy, which possibly occurs through a pathway that involves the expression of abnormally spliced TNNT2 variants.
“…Five studies included both children and adults in their report 36–39, 44 . Nineteen studies described the ethnicity of their participants 20, 23, 30–40, 43–45, 47, 50, 51 but, there were inconsistencies in reporting of race/ethnicity. For example, Weiss et al
33 described their participants either as Caucasian or not while Blanco et al
34 described their participants as White, Black and others.Figure 1PRISMA flow diagram showing the selection process and criteria of the included studies.
…”
Section: Resultsmentioning
confidence: 99%
“…Most studies using subjective outcomes defined cardiotoxicity as the presence of signs and symptoms requiring intervention 21–23, 30, 31, 33, 35–37, 41, 47–49 . In addition, some studies have used the left ventricular ejection fraction (LVEF) or shortening fraction (SF) as an objective measure, but the cut-off points varies.…”
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.
“…Five studies included both children and adults in their report 36–39, 44 . Nineteen studies described the ethnicity of their participants 20, 23, 30–40, 43–45, 47, 50, 51 but, there were inconsistencies in reporting of race/ethnicity. For example, Weiss et al
33 described their participants either as Caucasian or not while Blanco et al
34 described their participants as White, Black and others.Figure 1PRISMA flow diagram showing the selection process and criteria of the included studies.
…”
Section: Resultsmentioning
confidence: 99%
“…Most studies using subjective outcomes defined cardiotoxicity as the presence of signs and symptoms requiring intervention 21–23, 30, 31, 33, 35–37, 41, 47–49 . In addition, some studies have used the left ventricular ejection fraction (LVEF) or shortening fraction (SF) as an objective measure, but the cut-off points varies.…”
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.
“…Among the most extensively studied long‐term outcomes to date is anthracycline‐induced cardiotoxicity. Genes in which polymorphisms have been associated with cardiomyopathy and/or congestive heart failure include, but are not limited to, solute carrier family 2 member 3 ( SLC2A3) , ATP binding cassette (ABC) subfamily B member 1 ( ABCB1 ), ABCB4 , and ABCC1 , which are involved in drug transport; carbonyl reductase 3 ( CBR3 ), which is associated with the 2‐electron reduction of anthracyclines, a main route of anthracycline metabolism; CUGBP Elav‐like family member 4 ( CELF4 ), a regulator of alternate protein splicing, including cardiac troponin; and hyaluronan synthase 3 ( HAS3 ) and neutrophil cytosolic factor 4 ( NCF4 ), both of which are implicated in defense against reactive oxygen species . Similarly, studies among ALL survivors have indicated that polymorphisms in genes likely to affect the action of antileukemia medications, such as vitamin D receptor ( VDR ) and thymidylate synthetase ( TYMS ), are associated with osteonecrosis, while corticotropin‐releasing hormone receptor 1 ( CRHR1 ) polymorphisms alter the risk of bone density deficits .…”
The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapyrelated risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152.
“…Ten cohort studies reported cardiotoxicity outcomes across Europe and North America (Table 3). 3,[31][32][33][34][35][36][37][38][39] Two studies incorporated the ATP binding cassette subfamily C member (ABCC) family, with a risk associated with rs7627754, 31 rs3743527 TT genotype and in combination with the rs246221 TC/TT genotype. 34 Blanco et al found the expression of carbonyl reductase 3 (CBR3) was associated with cardiotoxicity, 36 whilst no association was found in the authors' previous study.…”
Many paediatric patients with cancer experience significant chemotherapy side effects. Predisposition to drug reactions is governed by single nucleotide polymorphisms (SNPs). We performed a systematic review of the literature from 2006 through 2016. Outcomes of interest included patient characteristics, cancer type drug of interest, genes investigated, toxicity identified and genetic polymorphisms implicated. The primary toxicities studied were neurotoxicity cardiotoxicity, osteonecrosis, and thromboembolism and hypersensitivity reactions. The retrieved studies were grouped according to toxicity reported and SNP associations. This review highlights the discoveries to date in pharmacogenomics and paediatric oncology along with highlighting some of the important limitations in the area.
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