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

Autor: Gábor T. Kovács, Dániel J. Erdélyi, Bálint Egyed, Nóra Kutszegi, Márta Hegyi, Gábor Ottóffy, Ágnes F. Semsei, Lili E. Fodor, Andrea Kelemen, Csaba Szalai, András Gézsi, Martina Ayaka Herlitschke, Judit C. Sági, Andrea Rzepiel
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Candidate gene
Anthracycline
0302 clinical medicine
Genotype
Cytochrome P-450 CYP3A
Medicine
Anthracyclines
Child
Cancer
Osteosarcoma
education.field_of_study
Antibiotics
Antineoplastic
Ejection fraction
Precursor Cell Lymphoblastic Leukemia-Lymphoma
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Multidrug Resistance-Associated Protein 2
Child
Preschool
030220 oncology & carcinogenesis
Female
Multidrug Resistance-Associated Proteins
Childhood cancer
Research Article
medicine.medical_specialty
Adolescent
Population
Bone Neoplasms
Single-nucleotide polymorphism
Genetic polymorphisms
Polymorphism
Single Nucleotide
lcsh:RC254-282
03 medical and health sciences
Internal medicine
Genetics
Humans
education
Cardiotoxicity
business.industry
Infant
Newborn
Infant
Bayes Theorem
medicine.disease
Logistic Models
030104 developmental biology
Heart failure
business
Zdroj: BMC Cancer, Vol 18, Iss 1, Pp 1-14 (2018)
BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-018-4629-6
Popis: Background The 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. Methods Echocardiography 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. Results Our 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. Conclusions Genetic variants in transporters and metabolic enzymes might modulate the individual risk to cardiac toxicity after chemotherapy. Electronic supplementary material The online version of this article (10.1186/s12885-018-4629-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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