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  • Mateos, Marion K.University of New South Wales,Sydney Children's Hospital (author)

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

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-05-19
  • MDPI AG,2020

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:e7e66dab-6fe1-4328-b9c6-77a3182c8ffd
  • https://lup.lub.lu.se/record/e7e66dab-6fe1-4328-b9c6-77a3182c8ffdURI
  • https://doi.org/10.3390/cancers12051285DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Tulstrup, MortenCopenhagen University Hospital (author)
  • Quinn, Michael C.J.QIMR Berghofer Medical Research Institute (author)
  • Tuckuviene, RutaAalborg University Hospital (author)
  • Marshall, Glenn M.University of New South Wales,Sydney Children's Hospital (author)
  • Gupta, RamneekTechnical University of Denmark (author)
  • Mayoh, ChelseaUniversity of New South Wales (author)
  • Wolthers, Benjamin O.Copenhagen University Hospital (author)
  • Barbaro, Pasquale M.University of Sydney (author)
  • Ruud, EllenOslo university hospital,University of Oslo (author)
  • Sutton, RosemaryUniversity of New South Wales (author)
  • Huttunen, PasiHelsinki University Children's Hospital (author)
  • Revesz, TamasRoyal Adelaide Hospital (author)
  • Trakymiene, Sonata S.Vilnius University (author)
  • Barbaric, DragaSydney Children's Hospital (author)
  • Tedgård, UlfLund University,Lunds universitet,Pediatrisk hematologi,Forskargrupper vid Lunds universitet,Paediatric Haematology Research Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)pedi-ute (author)
  • Giles, Jodie E.University of New South Wales (author)
  • Alvaro, FrankUniversity of Newcastle (author)
  • Jonsson, Olafur G.National University Hospital of Iceland (author)
  • Mechinaud, FrançoiseRoyal Children's Hospital, Melbourne,Hôpital universitaire Robert-Debré (author)
  • Saks, KadriTallinn Children's Hospital (author)
  • Catchpoole, DanielChildren's Hospital At Westmead (author)
  • Kotecha, Rishi S.Curtin University (author)
  • Dalla-Pozza, LucianoChildren's Hospital At Westmead (author)
  • Chenevix-Trench, GeorgiaQIMR Berghofer Medical Research Institute (author)
  • Trahair, Toby N.University of New South Wales,Sydney Children's Hospital (author)
  • Macgregor, StuartQIMR Berghofer Medical Research Institute (author)
  • Schmiegelow, KjeldUniversity of Copenhagen,Copenhagen University Hospital (author)
  • University of New South WalesSydney Children's Hospital (creator_code:org_t)

Related titles

  • In:Cancers: MDPI AG12:52072-6694

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