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Article: Association of GATA3 polymorphisms with minimal residual disease and relapse risk in childhood acute lymphoblastic leukemia

TitleAssociation of GATA3 polymorphisms with minimal residual disease and relapse risk in childhood acute lymphoblastic leukemia
Authors
Keywordsalleles
polymorphism
child
genome
genotype
Issue Date2020
PublisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/
Citation
JNCI: Journal of the National Cancer Institute, 2020, Epub 2020-09-07 How to Cite?
AbstractBackground: Minimal residual disease (MRD) after induction therapy is one of the strongest prognostic factors in childhood acute lymphoblastic leukemia (ALL), and MRD-directed treatment intensification improves survival. Little is known about the effects of inherited genetic variants on interpatient variability in MRD. Methods: A genome-wide association study was performed on 2597 children on the Children’s Oncology Group AALL0232 trial for high-risk B-cell ALL. Association between genotype and end-of-induction MRD levels was evaluated for 863 370 single nucleotide polymorphisms (SNPs), adjusting for genetic ancestry and treatment strata. Top variants were further evaluated in a validation cohort of 491 patients from the Children’s Oncology Group P9905 and 6 ALL trials. The independent prognostic value of single nucleotide polymorphisms was determined in multivariable analyses. All statistical tests were 2-sided. Results: In the discovery genome-wide association study, we identified a genome-wide significant association at the GATA3 locus (rs3824662, odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.35 to 1.84; P = 1.15 × 10-8 as a dichotomous variable). This association was replicated in the validation cohort (P = .003, MRD as a dichotomous variable). The rs3824662 risk allele independently predicted ALL relapse after adjusting for age, white blood cell count, and leukemia DNA index (P = .04 and .007 in the discovery and validation cohort, respectively) and remained prognostic when the analyses were restricted to MRD-negative patients (P = .04 and .03 for the discovery and validation cohorts, respectively). Conclusion: Inherited GATA3 variant rs3824662 strongly influences ALL response to remission induction therapy and is associated with relapse. This work highlights the potential utility of germline variants in upfront risk stratification in ALL.
Persistent Identifierhttp://hdl.handle.net/10722/288136
ISSN
2023 Impact Factor: 9.9
2023 SCImago Journal Rankings: 4.986
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHui, Z-
dc.contributor.authorLiu, APY-
dc.contributor.authorDevidas, M-
dc.contributor.authorLee, SHR-
dc.contributor.authorCao, X-
dc.contributor.authorPei, D-
dc.contributor.authorBorowitz, M-
dc.contributor.authorWood, B-
dc.contributor.authorGastier-Foster, JM-
dc.contributor.authorDai, Y-
dc.contributor.authorRaetz, E-
dc.contributor.authorLarsen, E-
dc.contributor.authorWinick, N-
dc.contributor.authorBowman, WP-
dc.contributor.authorKarol, S-
dc.contributor.authorYang, W-
dc.contributor.authorMartin, PL-
dc.contributor.authorCarroll, WL-
dc.contributor.authorPui, CH-
dc.contributor.authorMullighan, CG-
dc.contributor.authorEvans, WE-
dc.contributor.authorCheng, C-
dc.contributor.authorHunger, SP-
dc.contributor.authorRelling, MV-
dc.contributor.authorLoh, ML-
dc.contributor.authorYang, JJ-
dc.date.accessioned2020-10-05T12:08:24Z-
dc.date.available2020-10-05T12:08:24Z-
dc.date.issued2020-
dc.identifier.citationJNCI: Journal of the National Cancer Institute, 2020, Epub 2020-09-07-
dc.identifier.issn0027-8874-
dc.identifier.urihttp://hdl.handle.net/10722/288136-
dc.description.abstractBackground: Minimal residual disease (MRD) after induction therapy is one of the strongest prognostic factors in childhood acute lymphoblastic leukemia (ALL), and MRD-directed treatment intensification improves survival. Little is known about the effects of inherited genetic variants on interpatient variability in MRD. Methods: A genome-wide association study was performed on 2597 children on the Children’s Oncology Group AALL0232 trial for high-risk B-cell ALL. Association between genotype and end-of-induction MRD levels was evaluated for 863 370 single nucleotide polymorphisms (SNPs), adjusting for genetic ancestry and treatment strata. Top variants were further evaluated in a validation cohort of 491 patients from the Children’s Oncology Group P9905 and 6 ALL trials. The independent prognostic value of single nucleotide polymorphisms was determined in multivariable analyses. All statistical tests were 2-sided. Results: In the discovery genome-wide association study, we identified a genome-wide significant association at the GATA3 locus (rs3824662, odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.35 to 1.84; P = 1.15 × 10-8 as a dichotomous variable). This association was replicated in the validation cohort (P = .003, MRD as a dichotomous variable). The rs3824662 risk allele independently predicted ALL relapse after adjusting for age, white blood cell count, and leukemia DNA index (P = .04 and .007 in the discovery and validation cohort, respectively) and remained prognostic when the analyses were restricted to MRD-negative patients (P = .04 and .03 for the discovery and validation cohorts, respectively). Conclusion: Inherited GATA3 variant rs3824662 strongly influences ALL response to remission induction therapy and is associated with relapse. This work highlights the potential utility of germline variants in upfront risk stratification in ALL.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/-
dc.relation.ispartofJNCI: Journal of the National Cancer Institute-
dc.rightsPre-print: Journal Title] ©: [year] [owner as specified on the article] Published by Oxford University Press [on behalf of xxxxxx]. All rights reserved. Pre-print (Once an article is published, preprint notice should be amended to): This is an electronic version of an article published in [include the complete citation information for the final version of the Article as published in the print edition of the Journal.] Post-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here].-
dc.subjectalleles-
dc.subjectpolymorphism-
dc.subjectchild-
dc.subjectgenome-
dc.subjectgenotype-
dc.titleAssociation of GATA3 polymorphisms with minimal residual disease and relapse risk in childhood acute lymphoblastic leukemia-
dc.typeArticle-
dc.identifier.emailLiu, APY: apyliu@hku.hk-
dc.identifier.authorityLiu, APY=rp01357-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/jnci/djaa138-
dc.identifier.pmid32894760-
dc.identifier.scopuseid_2-s2.0-85099549940-
dc.identifier.hkuros315695-
dc.identifier.volumeEpub 2020-09-07-
dc.identifier.isiWOS:000648946500011-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl0027-8874-

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