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


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.

SUBMITTER: Perez-Andreu V 

PROVIDER: S-EPMC4304112 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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

Perez-Andreu Virginia V   Roberts Kathryn G KG   Xu Heng H   Smith Colton C   Zhang Hui H   Yang Wenjian W   Harvey Richard C RC   Payne-Turner Debbie D   Devidas Meenakshi M   Cheng I-Ming IM   Carroll William L WL   Heerema Nyla A NA   Carroll Andrew J AJ   Raetz Elizabeth A EA   Gastier-Foster Julie M JM   Marcucci Guido G   Bloomfield Clara D CD   Mrózek Krzysztof K   Kohlschmidt Jessica J   Stock Wendy W   Kornblau Steven M SM   Konopleva Marina M   Paietta Elisabeth E   Rowe Jacob M JM   Luger Selina M SM   Tallman Martin S MS   Dean Michael M   Burchard Esteban G EG   Torgerson Dara G DG   Yue Feng F   Wang Yanli Y   Pui Ching-Hon CH   Jeha Sima S   Relling Mary V MV   Evans William E WE   Gerhard Daniela S DS   Loh Mignon L ML   Willman Cheryl L CL   Hunger Stephen P SP   Mullighan Charles G CG   Yang Jun J JJ  

Blood 20141202 4


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 regr  ...[more]

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