Genome-Wide Association Meta-Analysis of Single-Nucleotide Polymorphisms and Symptomatic Venous Thromboembolism during Therapy for Acute Lymphoblastic Leukemia and Lymphoma in Caucasian Children.

Mateos, MK; Tulstrup, M; Quinn, MC; Tuckuviene, R; Marshall, GM; Gupta, R; Mayoh, C; Wolthers, BO; Barbaro, PM; Ruud, E; Sutton, R; Huttunen, P; Revesz, T; Trakymiene, SS; Barbaric, D; Tedgård, U; Giles, JE; Alvaro, F; Jonsson, OG; Mechinaud, F; Saks, K; Catchpoole, D; Kotecha, RS; Dalla-Pozza, L; Chenevix-Trench, G; Trahair, TN; MacGregor, S; Schmiegelow, K

Genome-Wide Association Meta-Analysis of Single-Nucleotide Polymorphisms and Symptomatic Venous Thromboembolism during Therapy for Acute Lymphoblastic Leukemia and Lymphoma in Caucasian Children.

Mateos, MK Tulstrup, M Quinn, MC Tuckuviene, R Marshall, GM Gupta, R Mayoh, C Wolthers, BO Barbaro, PM Ruud, E Sutton, R Huttunen, P Revesz, T Trakymiene, SS Barbaric, D Tedgård, U Giles, JE Alvaro, F Jonsson, OG Mechinaud, F Saks, K Catchpoole, D Kotecha, RS Dalla-Pozza, L Chenevix-Trench, G Trahair, TN MacGregor, S Schmiegelow, K

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Cancers, 2020, 12, (5), pp. 1285-1285
Issue Date:: 2020-05-19

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Field	Value	Language
dc.contributor.author	Mateos, MK
dc.contributor.author	Tulstrup, M
dc.contributor.author	Quinn, MC
dc.contributor.author	Tuckuviene, R
dc.contributor.author	Marshall, GM
dc.contributor.author	Gupta, R
dc.contributor.author	Mayoh, C
dc.contributor.author	Wolthers, BO
dc.contributor.author	Barbaro, PM
dc.contributor.author	Ruud, E
dc.contributor.author	Sutton, R
dc.contributor.author	Huttunen, P
dc.contributor.author	Revesz, T
dc.contributor.author	Trakymiene, SS
dc.contributor.author	Barbaric, D
dc.contributor.author	Tedgård, U
dc.contributor.author	Giles, JE
dc.contributor.author	Alvaro, F
dc.contributor.author	Jonsson, OG
dc.contributor.author	Mechinaud, F
dc.contributor.author	Saks, K
dc.contributor.author	Catchpoole, D
dc.contributor.author	Kotecha, RS
dc.contributor.author	Dalla-Pozza, L
dc.contributor.author	Chenevix-Trench, G
dc.contributor.author	Trahair, TN
dc.contributor.author	MacGregor, S
dc.contributor.author	Schmiegelow, K
dc.date.accessioned	2021-02-06T23:39:04Z
dc.date.available	2020-05-14
dc.date.available	2021-02-06T23:39:04Z
dc.date.issued	2020-05-19
dc.identifier.citation	Cancers, 2020, 12, (5), pp. 1285-1285
dc.identifier.issn	2072-6694
dc.identifier.issn	2072-6694
dc.identifier.uri	http://hdl.handle.net/10453/145887
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	Cancers
dc.relation.isbasedon	10.3390/cancers12051285
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights	©2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/
dc.subject	1112 Oncology and Carcinogenesis
dc.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.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Switzerland
utslib.for	1112 Oncology and Carcinogenesis
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	recently_added	*
dc.date.updated	2021-02-06T23:38:42Z
pubs.issue	5
pubs.publication-status	Published
pubs.volume	12
utslib.citation.issue	5

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.

Methods

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.

Results

No SNPs reached genome-wide significance (p < 5 × 10^-8) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p < 1 × 10^-6), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 × 10^-7) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 × 10^-7) that has been previously associated with risk of ischemic stroke, atherosclerosis, and early-onset coronary artery disease.

Conclusion

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/145887