Genome-wide association meta-analysis of single-nucleotide polymorphisms and symptomatic venous thromboembolism during therapy for acute lymphoblastic leukemia and lymphoma in caucasian children
(2020) In Cancers 12(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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020-05-19
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Acute lymphoblastic leukemia, Child, Genome-wide association study, Single-nucleotide polymorphism, Venous thromboembolism
- in
- Cancers
- volume
- 12
- issue
- 5
- article number
- 1285
- publisher
- MDPI AG
- external identifiers
-
- pmid:32438682
- scopus:85085388410
- ISSN
- 2072-6694
- DOI
- 10.3390/cancers12051285
- language
- English
- LU publication?
- yes
- id
- e7e66dab-6fe1-4328-b9c6-77a3182c8ffd
- date added to LUP
- 2020-06-24 09:39:33
- date last changed
- 2024-07-24 20:43:38
@article{e7e66dab-6fe1-4328-b9c6-77a3182c8ffd,
abstract = {{<p>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<sup>−8</sup>) in either cohort. Among the top 34 single-nucleotide polymorphisms (SNPs) (p < 1 × 10<sup>−6</sup>), two loci had concordant effects in both cohorts: ALOX15B (rs1804772) (MAF: 1%; p = 3.95 × 10<sup>−7</sup>) that influences arachidonic acid metabolism and thus platelet aggregation, and KALRN (rs570684) (MAF: 1%; p = 4.34 × 10<sup>−7</sup>) 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.</p>}},
author = {{Mateos, Marion K. and Tulstrup, Morten and Quinn, Michael C.J. and Tuckuviene, Ruta and Marshall, Glenn M. and Gupta, Ramneek and Mayoh, Chelsea and Wolthers, Benjamin O. and Barbaro, Pasquale M. and Ruud, Ellen and Sutton, Rosemary and Huttunen, Pasi and Revesz, Tamas and Trakymiene, Sonata S. and Barbaric, Draga and Tedgård, Ulf and Giles, Jodie E. and Alvaro, Frank and Jonsson, Olafur G. and Mechinaud, Françoise and Saks, Kadri and Catchpoole, Daniel and Kotecha, Rishi S. and Dalla-Pozza, Luciano and Chenevix-Trench, Georgia and Trahair, Toby N. and Macgregor, Stuart and Schmiegelow, Kjeld}},
issn = {{2072-6694}},
keywords = {{Acute lymphoblastic leukemia; Child; Genome-wide association study; Single-nucleotide polymorphism; Venous thromboembolism}},
language = {{eng}},
month = {{05}},
number = {{5}},
publisher = {{MDPI AG}},
series = {{Cancers}},
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}},
url = {{http://dx.doi.org/10.3390/cancers12051285}},
doi = {{10.3390/cancers12051285}},
volume = {{12}},
year = {{2020}},
}