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A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults.

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Pubmed体系：
作者：
Virginia Perez-Andreu[1] ; Kathryn G. Roberts[2] ; Heng Xu[1,3] ; Colton Smith[1] ; Hui Zhang[1] ; Wenjian Yang[1] ; Richard C. Harvey[4] ; Debbie Payne-Turner[2] ; Meenakshi Devidas[5] ; I-Ming Cheng[6] ; William L. Carroll[7] ; Nyla A. Heerema[8] ; Andrew J. Carroll[9] ; Elizabeth A. Raetz[10] ; Julie M. Gastier-Foster[11] ; Guido Marcucci[12] ; Clara D. Bloomfield[12] ; Krzysztof Mr´ozek[12] ; Jessica Kohlschmidt[12,13] ; Wendy Stock[14] ; Steven M. Kornblau[15] ; Marina Konopleva[16] ; Elisabeth Paietta[17] ; Jacob M. Rowe[18] ; Selina M. Luger[19] ; Martin S. Tallman[20] ; Michael Dean[21] ; Esteban G. Burchard[22] ; Dara G. Torgerson[22] ; Feng Yue[23] ; Yanli Wang[23] ; Ching-Hon Pui[24] ; Sima Jeha[24] ; Mary V. Relling[1] ; William E. Evans[1] ; Daniela S. Gerhard[25] ; Mignon L. Loh[26] ; Cheryl L. Willman[6] ; Stephen P. Hunger[27] ; Charles G. Mullighan[2,*2] ; Jun J. Yang[1,*1] ;
机构： [1]Department of Pharmaceutical Sciences,St. Jude Children’s Research Hospital, Memphis, TN [2]Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN [3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China [4]University of New Mexico Cancer Center, Albuquerque, NM [5]Department of Biostatistics, Colleges of Medicine, Public Health & Health Professions, University of Florida, Gainesville, FL [6]Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM [7]Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY [8]Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH [9]Department of Genetics, University of Alabama at Birmingham, Birmingham, AL [10]Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT [11]The Ohio State University, Nationwide Children’s Hospital, Columbus, OH [12]Comprehensive Cancer Center, The Ohio State University, Columbus, OH [13]Alliance of Clinical Trials in Oncology Statistics and Data Center, Mayo Clinic, Rochester [14]Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL [15]Section of Molecular Hematology & Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX [16]The University of Texas MD Anderson Cancer Center, Houston, TX [17]Department of Medicine (Oncology), Albert Einstein College of Medicine, Yeshiva University, New York, NY [18]Rambam Medical Center, Haifa, Israel [19]Hematologic Malignancies Program, Hematology-Oncology Division, University of Pennsylvania, Philadelphia, PA [20]Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY [21]Laboratory of Experimental Immunology, National Cancer Institute, Frederick, MD [22]Department of Bioengineering & Therapeutic Science and Department of Medicine, University of California, San Francisco, San Francisco, CA [23]Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA [24]Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN [25]Office of Cancer Genomics, National Cancer Institute, Bethesda, MD [26]Department of Pediatrics and the Helen Diller Family Cancer Center, University of California, San Francisco, San Francisco, CA [27]School of Medicine and Children’s Hospital, University of Colorado School of Medicine, Aurora, CO
出处：
DOI： 10.1182/blood-2014-09-595744
ISSN：

摘要：
Acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA) is characterized by distinct presenting features and inferior prognosis compared with pediatric ALL. We performed a genome-wide association study (GWAS) to comprehensively identify inherited genetic variants associated with susceptibility to AYA ALL. In the discovery GWAS, we compared genotype frequency at 635 297 single nucleotide polymorphisms (SNPs) in 308 AYA ALL cases and 6,661 non-ALL controls by using a logistic regression model with genetic ancestry as a covariate. SNPs that reached P ≤ 5 × 10(-8) in GWAS were tested in an independent cohort of 162 AYA ALL cases and 5,755 non-ALL controls. We identified a single genome-wide significant susceptibility locus in GATA3: rs3824662, odds ratio (OR), 1.77 (P = 2.8 × 10(-10)) and rs3781093, OR, 1.73 (P = 3.2 × 10(-9)). These findings were validated in the replication cohort. The risk allele at rs3824662 was most frequent in Philadelphia chromosome (Ph)-like ALL but also conferred susceptibility to non-Ph-like ALL in AYAs. In 1,827 non-selected ALL cases, the risk allele frequency at this SNP was positively correlated with age at diagnosis (P = 6.29 × 10(-11)). Our results from this first GWAS of AYA ALL susceptibility point to unique biology underlying leukemogenesis and potentially distinct disease etiology by age group.

基金：
This work was supported by the National Institutes of Health, National Cancer Institute grants CA145707, CA156449, CA21765, CA36401, CA98543, CA114766, CA98413, CA140729, CA176063, and HHSN261200800001E, the National Institute of General Medical Sciences grant GM92666, in part by the intramural Program of the National Cancer Institute, by a Stand Up to Cancer Innovative Research Grant, and by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital, by a St. Jude Children’s Research Hospital Academic Programs Special Fellowship and a SpanishMinistry of Education Fellowship Grant (V.P.-A.), by the American Society of Hematology Scholar Award and by the Order of St. Francis Foundation (J.J.Y.), and by a Leukemia and Lymphoma Society Fellow Award and Alex’s Lemonade Stand Foundation Young Investigator Award (K.G.R.). S.P.H. is the Ergen Family Chair in Pediatric Cancer, C.G.M. is a Pew Scholar in the Biomedical Sciences and a St. Baldrick’s Scholar, and H.Z. is a St. Baldrick’s International Scholar.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2015]版：
大类 | 1 区 医学
小类 | 1 区 血液学
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 血液学
第一作者：
第一作者机构： [1]Department of Pharmaceutical Sciences,St. Jude Children’s Research Hospital, Memphis, TN
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pharmaceutical Sciences,St. Jude Children’s Research Hospital, Memphis, TN [2]Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN [*1]Department of Pharmaceutical Sciences,MS313, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN38105-3678 [*2]Department of Pathology, MS 342, St. Jude Children’sResearch Hospital, 262DannyThomas Place, Memphis, TN 38105-3678
推荐引用方式(GB/T 7714)：
Virginia Perez-Andreu,Kathryn G. Roberts,Heng Xu,et al.A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults.[J].Blood.2015,125(4):680-6.doi:10.1182/blood-2014-09-595744.
APA：
Virginia Perez-Andreu,Kathryn G. Roberts,Heng Xu,Colton Smith,Hui Zhang...&Jun J. Yang.(2015).A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults..Blood,125,(4)
MLA：
Virginia Perez-Andreu,et al."A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults.".Blood 125..4(2015):680-6

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