Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/131943
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Type: Journal article
Title: Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in caucasian children
Author: Mateos, M.K.
Tulstrup, M.
Quinn, M.C.J.
Tuckuviene, R.
Marshall, G.M.
Gupta, R.
Mayoh, C.
Wolthers, B.O.
Barbaro, P.M.
Ruud, E.
Sutton, R.
Huttunen, P.
Revesz, T.
Trakymiene, S.S.
Barbaric, D.
Tedgård, U.
Giles, J.E.
Alvaro, F.
Jonsson, O.G.
Mechinaud, F.
et al.
Citation: Cancers, 2020; 12(5):1285-1-1285-15
Publisher: MDPI
Issue Date: 2020
ISSN: 2072-6694
2072-6694
Statement of
Responsibility: 
Marion K. Mateos, Morten Tulstrup, Michael CJ Quinn, Ruta Tuckuviene, Glenn M. Marshall, Ramneek Gupta
Abstract: Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied.<h4>Methods</h4>We undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included.<h4>Results</h4>No SNPs reached genome-wide significance (<i>p</i> < 5 × 10<sup>-8</sup>) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (<i>p</i> < 1 × 10<sup>-6</sup>), two loci had concordant effects in both cohorts: <i>ALOX15B</i> (rs1804772) (MAF: 1%; <i>p</i> = 3.95 × 10<sup>-7</sup>) that influences arachidonic acid metabolism and thus platelet aggregation, and <i>KALRN</i> (rs570684) (MAF: 1%; <i>p</i> = 4.34 × 10<sup>-7</sup>) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease.<h4>Conclusion</h4>This represents the largest GWAS meta-analysis conducted to date associating SNPs to VTE in children and adolescents treated on childhood ALL protocols. Validation of these findings is needed and may then lead to patient stratification for VTE preventive interventions. As VTE hemostasis involves multiple pathways, a more powerful GWAS is needed to detect combination of variants associated with VTE.
Keywords: acute lymphoblastic leukemia
child
genome-wide association study
single-nucleotide polymorphism
venous thromboembolism
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
DOI: 10.3390/cancers12051285
Appears in Collections:Aurora harvest 4
Paediatrics publications

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