Evidence map›Paper›PMID 29970035›Full record

ArticleBMC cancer2018

Possible roles of genetic variations in chemotherapy related cardiotoxicity in pediatric acute lymphoblastic leukemia and osteosarcoma.

Judit C Sági, Bálint Egyed, Andrea Kelemen, Nóra Kutszegi, Márta Hegyi, András Gézsi, Martina Ayaka Herlitschke, Andrea Rzepiel, Lili E Fodor, Gábor Ottóffy and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 5 pooled it
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 5 syntheses or guidelines pooled it, 46 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Judit C SágiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Bálint EgyedDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Andrea KelemenDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Nóra KutszegiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Márta HegyiSecond Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, Budapest, H-1094, Hungary.
András GézsiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Martina Ayaka HerlitschkeDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Andrea RzepielSecond Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, Budapest, H-1094, Hungary.
Lili E FodorDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Gábor OttóffyDepartment of Pediatrics, Oncohaematology Division, Pécs University, József Attila út 7, Pécs, H-7623, Hungary.
Gábor T KovácsSecond Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, Budapest, H-1094, Hungary.
Dániel J ErdélyiSecond Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, Budapest, H-1094, Hungary.
Csaba SzalaiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.
Ágnes F SemseiDepartment of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary. semsei.agnes@med.semmelweis-univ.hu.ORCID http://orcid.org/0000-0002-8709-2459
Semmelweis University · HUUniversity of Pecs · HU

Funding

National Research, Development and Innovation Office (NKFIH) K115861National Research, Development and Innovation Office (NKFIH) PD109200
6 · The paper itself

Abstract

backgroundThe treatment of acute lymphoblastic leukemia (ALL) and osteosarcoma (OSC) is very effective: the vast majority of patients recover and survive for decades. However, they still need to face serious adverse effects of chemotherapy. One of these is cardiotoxicity which may lead to progressive heart failure in the long term. Cardiotoxicity is contributed mainly to the use of anthracyclines and might have genetic risk factors. Our goal was to test the association between left ventricular function and genetic variations of candidate genes.

methodsEchocardiography data from medical records of 622 pediatric ALL and 39 OSC patients were collected from the period 1989-2015. Fractional shortening (FS) and ejection fraction (EF) were determined, 70 single nucleotide polymorphisms (SNPs) in 26 genes were genotyped. Multivariate logistic regression and multi-adjusted general linear model were performed to investigate the influence of genetic polymorphisms on the left ventricular parameters. Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) method was applied to test for the potential interaction of the studied cofactors and SNPs.

resultsOur results indicate that variations in ABCC2, CYP3A5, NQO1, SLC22A6 and SLC28A3 genes might influence the left ventricular parameters. CYP3A5 rs4646450 TT was 17% among ALL cases with FS lower than 28, and 3% in ALL patients without pathological FS (p = 5.60E-03; OR = 6.94 (1.76-27.39)). SLC28A3 rs7853758 AA was 12% in ALL cases population, while only 1% among controls (p = 6.50E-03; OR = 11.56 (1.98-67.45)). Patients with ABCC2 rs3740066 GG genotype had lower FS during the acute phase of therapy and 5-10 years after treatment (p = 7.38E-03, p = 7.11E-04, respectively). NQO1 rs1043470 rare T allele was associated with lower left ventricular function in the acute phase and 5-10 years after the diagnosis (p = 4.28E-03 and 5.82E-03, respectively), and SLC22A6 gene rs6591722 AA genotype was associated with lower mean FS (p = 1.71E-03), 5-10 years after the diagnosis.

conclusionsGenetic variants in transporters and metabolic enzymes might modulate the individual risk to cardiac toxicity after chemotherapy.

Indexed as

Polymorphism, Single NucleotideAdolescentAnthracyclinesAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsBayes TheoremBone NeoplasmsCardiotoxicityChildChild, PreschoolCytochrome P-450 CYP3AFemaleGenotypeHumansInfantInfant, NewbornABCC2 protein, humanAnthracyclinesAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsCytochrome P-450 CYP3AMultidrug Resistance-Associated Protein 2AnthracyclineCancerCardiotoxicityChildhood cancerGenetic polymorphisms

Identifiers

PMID29970035
PMCPMC6029426
OpenAlexW2810427807

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.