Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in Caucasian children /

Marion K Mateos; Morten Tulstrup; Michael Cj Quinn; Ruta Tuckuviene; Glenn M Marshall; Ramneek Gupta; Chelsea Mayoh; Benjamin O Wolthers; Pasquale M Barbaro; Ellen Ruud; Rosemary Sutton; Pasi Huttunen; Tamas Revesz; Sonata Šaulytė Trakymienė; Draga Barbaric; Ulf Tedgård; Jodie E Giles; Frank Alvaro; Olafur G Jonsson; Françoise Mechinaud; Kadri Saks; Daniel Catchpoole; Rishi S Kotecha; Luciano Dalla-Pozza; Georgia Chenevix-Trench; Toby N Trahair; Stuart MacGregor; Kjeld Schmiegelow

doi:10.3390/cancers12051285

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 /
Authors	Mateos, Marion K ; Tulstrup, Morten ; Quinn, Michael Cj ; Tuckuviene, Ruta ; Marshall, Glenn M ; Gupta, Ramneek ; Mayoh, Chelsea ; Wolthers, Benjamin O ; Barbaro, Pasquale M ; Ruud, Ellen ; Sutton, Rosemary ; Huttunen, Pasi ; Revesz, Tamas ; Šaulytė Trakymienė, Sonata ; Barbaric, Draga ; Tedgård, Ulf ; Giles, Jodie E ; Alvaro, Frank ; Jonsson, Olafur G ; Mechinaud, Françoise ; Saks, Kadri ; Catchpoole, Daniel ; Kotecha, Rishi S ; Dalla-Pozza, Luciano ; Chenevix-Trench, Georgia ; Trahair, Toby N ; MacGregor, Stuart ; Schmiegelow, Kjeld
DOI	10.3390/cancers12051285
Full Text
Is Part of	Cancers.. Basel : MDPI. 2020, vol. 12, iss. 5, art. no. 1285, p. [1-15].. ISSN 2072-6694
Keywords [eng]	acute lymphoblastic leukemia ; child ; genome-wide association study ; single-nucleotide polymorphism ; venous thromboembolism
Abstract [eng]	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.
Published	Basel : MDPI
Type	Journal article
Language	English
Publication date	2020
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„Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in Caucasian children /“