A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults
Year: 2014
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood
Authors: Virginia Perez-Andreu, Kathryn G. Roberts, Heng Xu, Colton Smith, Hui Zhang, Wenjian Yang, Richard C. Harvey, Debbie Payne-Turner, Meenakshi Devidas, I-Ming Cheng, William L. Carroll, Nyla A. Heerema, Andrew J. Carroll, Elizabeth A. Raetz, Julie M. Gastier-Foster, Guido Marcucci, Clara D. Bloomfield, Krzysztof Mrózek, Jessica Kohlschmidt, Wendy Stock, Steven M. Kornblau, Marina Konopleva, Elisabeth Paietta, Jacob M. Rowe, Selina M. Luger, Martin S. Tallman, Michael Dean, Esteban G. Burchard, Dara G. Torgerson, Feng Yue, Yanli Wang, Ching-Hon Pui, Sima Jeha, Mary V. Relling, William E. Evans, Daniela S. Gerhard, Mignon L. Loh, Cheryl L. Willman, Stephen P. Hunger, Charles G. Mullighan, Jun J. Yang
Institutions: St. Jude Children's Research Hospital, Sichuan University, West China Medical Center of Sichuan University, State Key Laboratory of Biotherapy, UNM Comprehensive Cancer Center, University of Florida Health, University of Florida, University of New Mexico, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, The Ohio State University, University of Alabama at Birmingham, University of Utah, Huntsman Cancer Institute, Nationwide Children's Hospital, Mayo Clinic, University of Chicago, The University of Texas MD Anderson Cancer Center, Albert Einstein College of Medicine, Yeshiva University, Rambam Health Care Campus, University of Pennsylvania, Memorial Sloan Kettering Cancer Center, Frederick National Laboratory for Cancer Research, National Cancer Institute, University of California, San Francisco, Pennsylvania State University, UCSF Helen Diller Family Comprehensive Cancer Center, Children's Hospital Colorado, University of Colorado Anschutz
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1104154511, G1197250460, G1399567684, G1504112592, G1581977058, G1600560672, G1771393403, G1860110607, ECOG-ACRIN Network Group Operations Center, G2117365975, G2215807464, G2679961467, G2688579988, G2901481919, Pharmacogenomics of Childhood Leukemia ALL, G386607036, G3942302684, G421865639, Children's Oncology Group Statistics and Data Center, G46020690, G4674020032, MOLECULAR SIGNATURES FOR OUTCOME PREDICTION AND THERAPEUTIC TARGETING IN ALL, G5113398931, G5150888020, G5888954722, G609259107, G667558184, PHARMACOGENOMICS OF CHILDHOOD LEUKEMIA (ALL), ECOG-ACRIN INTEGRATED LEUKEMIA TRANSLATIONAL RESEARCH CENTER, G860380395, Cancer Center Support Grant (CCSG), G997771125
OpenAlex ID: W2026966240