2021
Genome-wide trans-ethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia
Jeon S, de Smith AJ, Li S, Chen M, Chan TF, Muskens IS, Morimoto LM, DeWan AT, Mancuso N, Metayer C, Ma X, Wiemels JL, Chiang CWK. Genome-wide trans-ethnic meta-analysis identifies novel susceptibility loci for childhood acute lymphoblastic leukemia. Leukemia 2021, 36: 865-868. PMID: 34750507, PMCID: PMC9075725, DOI: 10.1038/s41375-021-01465-1.Peer-Reviewed Original ResearchMeSH KeywordsChildGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaGenetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia
Kachuri L, Jeon S, DeWan AT, Metayer C, Ma X, Witte JS, Chiang CWK, Wiemels JL, de Smith AJ. Genetic determinants of blood-cell traits influence susceptibility to childhood acute lymphoblastic leukemia. American Journal Of Human Genetics 2021, 108: 1823-1835. PMID: 34469753, PMCID: PMC8546033, DOI: 10.1016/j.ajhg.2021.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkers, TumorBlood PlateletsCase-Control StudiesChildFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLymphocytesMaleMendelian Randomization AnalysisMiddle AgedMonocytesNeutrophilsPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisProspective StudiesQuantitative Trait LociUnited KingdomConceptsTrait-associated variantsMulti-trait GWASBlood cell homeostasisWide association studyGenetic risk lociTrait variationHematologic traitsRisk lociAssociation studiesCell typesGenetic determinantsLociInfluence susceptibilityUK BiobankMendelian randomization analysisGWASEtiological relevanceRandomization analysisTraitsHomeostasisSusceptibilityAcute lymphoblastic leukemia
2020
Germline cancer predisposition variants and pediatric glioma: a population-based study in California
Muskens IS, de Smith AJ, Zhang C, Hansen HM, Morimoto L, Metayer C, Ma X, Walsh KM, Wiemels JL. Germline cancer predisposition variants and pediatric glioma: a population-based study in California. Neuro-Oncology 2020, 22: 864-874. PMID: 31970404, PMCID: PMC7283023, DOI: 10.1093/neuonc/noaa014.Peer-Reviewed Original ResearchConceptsCancer predisposition genesPathogenic germline variantsPathogenic variantsGermline variantsNeurofibromatosis 1Pediatric astrocytomasCandidate cancer predisposition genesPredisposition genesGene burden testingPediatric glioblastomaPediatric cancer predispositionMalignant pediatric brain tumorTertiary referral centerPopulation-based studyPediatric brain tumorsCancer predisposition variantsPediatric glioma patientsRare germline variantsTumor protein 53Whole-exome sequencingExome-wide levelReferral centerAstrocytoma patientsGlioma patientsBrain tumors
2019
Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome
Brown AL, de Smith AJ, Gant VU, Yang W, Scheurer ME, Walsh KM, Chernus JM, Kallsen NA, Peyton SA, Davies GE, Ehli EA, Winick N, Heerema NA, Carroll AJ, Borowitz MJ, Wood BL, Carroll WL, Raetz EA, Feingold E, Devidas M, Barcellos LF, Hansen HM, Morimoto L, Kang AY, Smirnov I, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson P, Spector LG, Pombo-de-Oliveira MS, DeWan AT, Mullighan CG, Hunger SP, Pui CH, Loh ML, Zwick ME, Metayer C, Ma X, Mueller BA, Sherman SL, Wiemels JL, Relling MV, Yang JJ, Lupo PJ, Rabin KR. Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome. Blood 2019, 134: 1227-1237. PMID: 31350265, PMCID: PMC6788009, DOI: 10.1182/blood.2018890764.Peer-Reviewed Original ResearchMeSH KeywordsChildCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDown SyndromeGATA3 Transcription FactorGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIkaros Transcription FactorPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsConceptsFirst genome-wide association studySusceptibility lociGenome-wide association studiesGenome-wide significanceFurther biological insightsGenetic variationEnhancer activityRisk lociBiological insightsLymphoblastoid cell linesAssociation studiesDifferential protein bindingFunctional significanceLociRisk allele frequenciesCell linesAllele frequenciesHigh penetranceRisk allelesProtein bindingCDKN2AGenetic susceptibilityHigher proliferationPenetranceAllele associationsHeritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome
de Smith AJ, Walsh KM, Morimoto LM, Francis SS, Hansen HM, Jeon S, Gonseth S, Chen M, Sun H, Luna-Fineman S, Antillón F, Girón V, Kang AY, Smirnov I, Shao X, Whitehead TP, Barcellos LF, Jolly KW, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson PD, Pombo-de-Oliveira MS, Spector LG, DeWan AT, Mueller BA, Chiang C, Metayer C, Ma X, Wiemels JL. Heritable variation at the chromosome 21 gene ERG is associated with acute lymphoblastic leukemia risk in children with and without Down syndrome. Leukemia 2019, 33: 2746-2751. PMID: 31296947, PMCID: PMC6858994, DOI: 10.1038/s41375-019-0514-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentCaliforniaCase-Control StudiesChildChild, PreschoolChromosomes, Human, Pair 21Down SyndromeFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGuatemalaHaplotypesHispanic or LatinoHumansInfantInfant, NewbornMalePolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaPrincipal Component AnalysisRisk FactorsTranscriptional Regulator ERG
2018
BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia
de Smith AJ, Walsh KM, Francis SS, Zhang C, Hansen HM, Smirnov I, Morimoto L, Whitehead TP, Kang A, Shao X, Barcellos LF, McKean‐Cowdin R, Zhang L, Fu C, Wang R, Yu H, Hoh J, Dewan AT, Metayer C, Ma X, Wiemels JL. BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia. International Journal Of Cancer 2018, 143: 2647-2658. PMID: 29923177, PMCID: PMC6235695, DOI: 10.1002/ijc.31622.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCaliforniaCell Cycle ProteinsChildChromosome MappingChromosomes, Human, Pair 10Core Binding Factor Alpha 1 SubunitEnhancer Elements, GeneticFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansK562 CellsLinkage DisequilibriumLogistic ModelsMalePhosphotransferases (Alcohol Group Acceptor)Polycomb Repressive Complex 1Polymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTrans-ActivatorsYoung AdultConceptsFunctional variantsSingle nucleotide polymorphism (SNP) imputationGenome-wide significant associationGenome-wide association studiesStem cell enhancerPutative functional variantsChIP-seq dataRegion of associationGenetic Epidemiology ResearchChromosome 10p12Transcription factorsAdmixed AmericansCell enhancerLead SNPAssociation studiesSNP associationsAssociation analysisLinkage disequilibriumBMI1SNPsTight linkage disequilibriumPIP4K2APreferential bindingRisk allelesVariantsGWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21
Wiemels JL, Walsh KM, de Smith AJ, Metayer C, Gonseth S, Hansen HM, Francis SS, Ojha J, Smirnov I, Barcellos L, Xiao X, Morimoto L, McKean-Cowdin R, Wang R, Yu H, Hoh J, DeWan AT, Ma X. GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21. Nature Communications 2018, 9: 286. PMID: 29348612, PMCID: PMC5773513, DOI: 10.1038/s41467-017-02596-9.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentCaliforniaChild, PreschoolChromosomes, Human, Pair 17Chromosomes, Human, Pair 8FemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHispanic or LatinoHumansInfantInfant, NewbornMalePolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaRisk FactorsConceptsNew risk lociRisk lociGenome-wide association studiesGrowth regulation pathwaysGenetic associationAcute lymphoblastic leukemiaNovel genetic associationsChildhood acute lymphoblastic leukemiaGenetic Epidemiology ResearchTranscription factorsStrong genetic associationGene expressionAssociation studiesLymphocyte developmentMYC oncogeneChromosome 17q12Oncology GroupLymphoblastic leukemiaLociChildren's Oncology GroupCalifornia Childhood Leukemia StudyChildhood Leukemia StudyStructural contactsYear of birthNon-Latino whites
2015
A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution
Walsh KM, de Smith AJ, Hansen HM, Smirnov IV, Gonseth S, Endicott AA, Xiao J, Rice T, Fu CH, McCoy LS, Lachance DH, Eckel-Passow JE, Wiencke JK, Jenkins RB, Wrensch MR, Ma X, Metayer C, Wiemels JL. A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution. Cancer Research 2015, 75: 4884-4894. PMID: 26527286, PMCID: PMC4651745, DOI: 10.1158/0008-5472.can-15-1105.Peer-Reviewed Original ResearchConceptsAcute lymphoblastic leukemiaChildhood acute lymphoblastic leukemiaLymphoblastic leukemiaCancer riskRisk allelesGeneral cancer riskPancreatic cancer riskGenome-wide association studiesCase-control populationCDKN2A variantsProtective allelesTumor growthClonal expansionChromosome 9p21.3Hispanic childrenMissense polymorphismStrong riskMissense variantsClonal evolutionRiskLeukemiaTumorsAllelic imbalanceEuropean ancestryPolymorphism
2014
Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B‐cell acute lymphoblastic leukemia
Walsh KM, de Smith A, Welch TC, Smirnov I, Cunningham MJ, Ma X, Chokkalingam AP, Dahl GV, Roberts W, Barcellos LF, Buffler PA, Metayer C, Wiemels JL. Genomic ancestry and somatic alterations correlate with age at diagnosis in Hispanic children with B‐cell acute lymphoblastic leukemia. American Journal Of Hematology 2014, 89: 721-725. PMID: 24753091, PMCID: PMC4069235, DOI: 10.1002/ajh.23727.Peer-Reviewed Original Research
2013
Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children
Walsh KM, Chokkalingam AP, Hsu LI, Metayer C, de Smith AJ, Jacobs DI, Dahl GV, Loh ML, Smirnov IV, Bartley K, Ma X, Wiencke JK, Barcellos LF, Wiemels JL, Buffler PA. Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children. Leukemia 2013, 27: 2416-2419. PMID: 23615557, PMCID: PMC3864612, DOI: 10.1038/leu.2013.130.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAllelesChildGenetic Predisposition to DiseaseGenome, HumanHumansIndians, North AmericanLymphoma, B-Cell
2012
HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk
Urayama KY, Chokkalingam AP, Metayer C, Ma X, Selvin S, Barcellos LF, Wiemels JL, Wiencke JK, Taylor M, Brennan P, Dahl GV, Moonsamy P, Erlich HA, Trachtenberg E, Buffler PA. HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk. Blood 2012, 120: 3039-3047. PMID: 22923493, PMCID: PMC3471514, DOI: 10.1182/blood-2012-01-404723.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultCase-Control StudiesChildChild, PreschoolFemaleGenetic Predisposition to DiseaseGenetic VariationGenotypeHispanic or LatinoHLA-DP alpha-ChainsHLA-DP beta-ChainsHumansImmunologic FactorsInfantMalePrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisRisk FactorsWhite PeopleYoung AdultConceptsAcute lymphoblastic leukemiaImmune modulationChildhood acute lymphoblastic leukemiaChildhood acute lymphoblastic leukemia riskAcute lymphoblastic leukemia riskEarly immune modulationHuman leukocyte antigen (HLA) genesLowest exposure categoryLogistic regression analysisEtiology of childhoodNon-Hispanic whitesHLA-DPB1 geneRace/ethnicityInfectious exposureLymphoblastic leukemiaImmune mechanismsExposure categoriesHispanic ethnicityLeukemia riskGenetic susceptibility lociHLA-DPA1Immune systemHispanic childrenRegression analysisEvidence of interaction
2011
Genetic variation in nucleotide excision repair pathway genes, pesticide exposure and prostate cancer risk
Barry KH, Koutros S, Andreotti G, Sandler DP, Burdette LA, Yeager M, Freeman L, Lubin JH, Ma X, Zheng T, Alavanja MC, Berndt SI. Genetic variation in nucleotide excision repair pathway genes, pesticide exposure and prostate cancer risk. Carcinogenesis 2011, 33: 331-337. PMID: 22102698, PMCID: PMC3271261, DOI: 10.1093/carcin/bgr258.Peer-Reviewed Original ResearchConceptsProstate cancer riskCancer riskSingle nucleotide polymorphismsPesticide exposurePesticide applicatorsPesticide manufacturing workersCase-control studyInteraction p valueProstate cancer casesNucleotide excision repair pathway genesWild-type TT genotypeLogistic regression modelsHuman biomonitoring studiesCancer casesLifetime daysTT genotypeERCC1 rs2298881Male controlsFalse discovery rate methodIntensity scoresSignificant associationNucleotide excision repair pathwayGenotype groupsManufacturing workersUnderlying mechanism
2006
Cytogenetics of Hispanic and White Children with Acute Lymphoblastic Leukemia in California
Aldrich MC, Zhang L, Wiemels JL, Ma X, Loh ML, Metayer C, Selvin S, Feusner J, Smith MT, Buffler PA. Cytogenetics of Hispanic and White Children with Acute Lymphoblastic Leukemia in California. Cancer Epidemiology Biomarkers & Prevention 2006, 15: 578-581. PMID: 16537719, DOI: 10.1158/1055-9965.epi-05-0833.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAge DistributionCaliforniaChildChild, PreschoolCohort StudiesCore Binding Factor Alpha 2 SubunitCytogeneticsFemaleGene Expression Regulation, NeoplasticGenetic MarkersGenetic Predisposition to DiseaseHispanic or LatinoHumansIn Situ Hybridization, FluorescenceIncidenceInfantMaleOncogene Proteins, FusionPloidiesPrecursor Cell Lymphoblastic Leukemia-LymphomaProbabilityProspective StudiesRisk FactorsSensitivity and SpecificitySeverity of Illness IndexSex DistributionSurvival RateWhite PeopleConceptsAcute lymphoblastic leukemia patientsNon-Hispanic whitesLymphoblastic leukemia patientsLeukemia patientsB-lineage acute lymphoblastic leukemia patientsNorthern California Childhood Leukemia StudyPopulation-based studyAcute lymphoblastic leukemiaCalifornia Childhood Leukemia StudyChildhood Leukemia StudyChildhood leukemia patientsEthnic-specific risk factorsTEL-AML1 translocationSitu hybridization findingsTumor genetic characteristicsLymphoblastic leukemiaRisk factorsEpidemiologic studiesHigh hyperdiploidyTEL-AML1Childhood leukemiaCytogenetic profilePatientsMLL rearrangementsLeukemia Study