Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study

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Jarvis , K B , LeBlanc , M , Tulstrup , M , Nielsen , R L , Albertsen , B K , Gupta , R , Huttunen , P , Jonsson , O G , Rank , C U , Ranta , S , Ruud , E , Saks , K , Trakymiene , S S , Tuckuviene , R & Schmiegelow , K 2019 , ' Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study ' , Thrombosis Research , vol. 184 , pp. 92-98 . https://doi.org/10.1016/j.thromres.2019.11.002

Title: Candidate single nucleotide polymorphisms and thromboembolism in acute lymphoblastic leukemia - A NOPHO ALL2008 study
Author: Jarvis, Kirsten Brunsvig; LeBlanc, Marissa; Tulstrup, Morten; Nielsen, Rikke Linnemann; Albertsen, Birgitte Klug; Gupta, Ramneek; Huttunen, Pasi; Jonsson, Olafur Gisli; Rank, Cecilie Utke; Ranta, Susanna; Ruud, Ellen; Saks, Kadri; Trakymiene, Sonata Saulyte; Tuckuviene, Ruta; Schmiegelow, Kjeld
Contributor organization: HUS Children and Adolescents
Clinicum
Children's Hospital
Date: 2019-12
Language: eng
Number of pages: 7
Belongs to series: Thrombosis Research
ISSN: 0049-3848
DOI: https://doi.org/10.1016/j.thromres.2019.11.002
URI: http://hdl.handle.net/10138/323892
Abstract: Introduction: Thromboembolism is a serious toxicity of acute lymphoblastic leukemia treatment, and contributes to substantial morbidity and mortality. Several single nucleotide polymorphisms have been associated with thromboembolism in the general population; however, their impact in patients with acute lymphoblastic leukemia, particularly in children, remains uncertain. Materials and methods: We collected constitutional DNA and prospectively registered thromboembolic events in 1252 patients, 1-45 years, with acute lymphoblastic leukemia included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol in the Nordic and Baltic countries (7/2008-7/2016). Based on previously published data and a priori power calculations, we selected four single nucleotide polymorphisms: F5 rs6025, F11 rs2036914, FGG rs2066865, and ABO rs8176719. Results: The 2.5 year cumulative incidence of thromboembolism was 7.1% (95% confidence interval (CI) 5.6-8.5). F11 rs2036914 was associated with thromboembolism (hazard ratio (HR) 1.52, 95%CI 1.11-2.07) and there was a borderline significant association for FGG rs2066865 (HR 1.37, 95%CI 0.99-1.91), but no association for ABO rs8176719 or F5 rs6025 in multiple cox regression. A genetic risk score based on F11 rs2036914 and FGG rs2066865 was associated with thromboembolism (HR 1.45 per risk allele, 95%CI 1.15-1.81), the association was strongest in adolescents 10.0-17.9 years (HR 1.64). Conclusion: If validated, a F11 rs2036914/FGG rs2066865 risk prediction model should be tested as a stratification tool for prevention of thromboembolism in patients with acute lymphoblastic leukemia.
Subject: Thromboembolism
Single nucleotide polymorphisms
Acute lymphoblastic leukemia
INCIDENT VENOUS THROMBOEMBOLISM
DEVELOPMENTAL HEMOSTASIS
RISK-FACTORS
BLOOD-GROUP
CHILDREN
FIBRINOGEN
THROMBOSIS
METAANALYSIS
ASSOCIATION
VARIANTS
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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