ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia

Heng Xu, Cheng Cheng, Meenakshi Devidas, Deqing Pei, Yiping Fan, Wenjian Yang, Geoff Neale, Paul Scheet, Esteban G. Burchard, Dara G. Torgerson, Celeste Eng, Michael Dean, Frederico Antillon, Naomi J. Winick, Paul L. Martin, Cheryl L. Willman, Bruce M. Camitta, Gregory H. Reaman, William L. Carroll, Mignon LohWilliam E. Evans, Ching Hon Pui, Stephen P. Hunger, Mary V. Relling, Jun J. Yang

Research output: Contribution to journalArticle

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Abstract

Purpose: Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods: We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results: Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10 -20in whites; P = 1 × 10 -6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10 -8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion: ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.

Original languageEnglish (US)
Pages (from-to)751-757
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number7
DOIs
StatePublished - Mar 1 2012

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Genetic Polymorphisms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Single Nucleotide Polymorphism
Hispanic Americans
Incidence
North American Indians
Genotype
Alleles
Recurrence
Multivariate Analysis
Clinical Trials
Genome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. / Xu, Heng; Cheng, Cheng; Devidas, Meenakshi; Pei, Deqing; Fan, Yiping; Yang, Wenjian; Neale, Geoff; Scheet, Paul; Burchard, Esteban G.; Torgerson, Dara G.; Eng, Celeste; Dean, Michael; Antillon, Frederico; Winick, Naomi J.; Martin, Paul L.; Willman, Cheryl L.; Camitta, Bruce M.; Reaman, Gregory H.; Carroll, William L.; Loh, Mignon; Evans, William E.; Pui, Ching Hon; Hunger, Stephen P.; Relling, Mary V.; Yang, Jun J.

In: Journal of Clinical Oncology, Vol. 30, No. 7, 01.03.2012, p. 751-757.

Research output: Contribution to journalArticle

Xu, H, Cheng, C, Devidas, M, Pei, D, Fan, Y, Yang, W, Neale, G, Scheet, P, Burchard, EG, Torgerson, DG, Eng, C, Dean, M, Antillon, F, Winick, NJ, Martin, PL, Willman, CL, Camitta, BM, Reaman, GH, Carroll, WL, Loh, M, Evans, WE, Pui, CH, Hunger, SP, Relling, MV & Yang, JJ 2012, 'ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia', Journal of Clinical Oncology, vol. 30, no. 7, pp. 751-757. https://doi.org/10.1200/JCO.2011.38.0345
Xu, Heng ; Cheng, Cheng ; Devidas, Meenakshi ; Pei, Deqing ; Fan, Yiping ; Yang, Wenjian ; Neale, Geoff ; Scheet, Paul ; Burchard, Esteban G. ; Torgerson, Dara G. ; Eng, Celeste ; Dean, Michael ; Antillon, Frederico ; Winick, Naomi J. ; Martin, Paul L. ; Willman, Cheryl L. ; Camitta, Bruce M. ; Reaman, Gregory H. ; Carroll, William L. ; Loh, Mignon ; Evans, William E. ; Pui, Ching Hon ; Hunger, Stephen P. ; Relling, Mary V. ; Yang, Jun J. / ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 7. pp. 751-757.
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abstract = "Purpose: Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods: We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95{\%} European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10{\%} Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results: Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10 -20in whites; P = 1 × 10 -6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10 -8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion: ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.",
author = "Heng Xu and Cheng Cheng and Meenakshi Devidas and Deqing Pei and Yiping Fan and Wenjian Yang and Geoff Neale and Paul Scheet and Burchard, {Esteban G.} and Torgerson, {Dara G.} and Celeste Eng and Michael Dean and Frederico Antillon and Winick, {Naomi J.} and Martin, {Paul L.} and Willman, {Cheryl L.} and Camitta, {Bruce M.} and Reaman, {Gregory H.} and Carroll, {William L.} and Mignon Loh and Evans, {William E.} and Pui, {Ching Hon} and Hunger, {Stephen P.} and Relling, {Mary V.} and Yang, {Jun J.}",
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TY - JOUR

T1 - ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia

AU - Xu, Heng

AU - Cheng, Cheng

AU - Devidas, Meenakshi

AU - Pei, Deqing

AU - Fan, Yiping

AU - Yang, Wenjian

AU - Neale, Geoff

AU - Scheet, Paul

AU - Burchard, Esteban G.

AU - Torgerson, Dara G.

AU - Eng, Celeste

AU - Dean, Michael

AU - Antillon, Frederico

AU - Winick, Naomi J.

AU - Martin, Paul L.

AU - Willman, Cheryl L.

AU - Camitta, Bruce M.

AU - Reaman, Gregory H.

AU - Carroll, William L.

AU - Loh, Mignon

AU - Evans, William E.

AU - Pui, Ching Hon

AU - Hunger, Stephen P.

AU - Relling, Mary V.

AU - Yang, Jun J.

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Purpose: Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods: We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results: Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10 -20in whites; P = 1 × 10 -6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10 -8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion: ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.

AB - Purpose: Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods: We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results: Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10 -20in whites; P = 1 × 10 -6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10 -8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion: ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease.

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