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

Kirsten Brunsvig Jarvis*, Marissa LeBlanc, Morten Tulstrup, Rikke Linnemann Nielsen, Birgitte Klug Albertsen, Ramneek Gupta, Pasi Huttunen, Ólafur Gisli Jónsson, Cecilie Utke Rank, Susanna Ranta, Ellen Ruud, Kadri Saks, Sonata Saulyte Trakymiene, Ruta Tuckuviene, Kjeld Schmiegelow

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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).
Original languageEnglish
JournalThrombosis Research
Volume184
Pages (from-to)92-98
ISSN0049-3848
DOIs
Publication statusPublished - 2019

Keywords

  • Thromboembolism
  • Single nucleotide polymorphisms
  • Acute lymphoblastic leukemia

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