Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics
Year: 2018
Type: article
Study design: Observational Study
Abstract: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Characterized by high levels of Native American ancestry, Hispanics are disproportionally affected by this cancer with high incidence and inferior survival. However, the genetic basis for this disparity remains poorly understood because of a paucity of genome-wide investigation of ALL in Hispanics. Performing a genome-wide association study (GWAS) in 940 Hispanic children with ALL and 681 ancestry-matched non-ALL controls, we identified a novel susceptibility locus in the ERG gene (rs2836365; P = 3.76 × 10−8; odds ratio [OR] = 1.56), with independent validation (P = .01; OR = 1.43). Imputation analyses pointed to a single causal variant driving the association signal at this locus overlapping with putative regulatory DNA elements. The effect size of the ERG risk variant rose with increasing Native American genetic ancestry. The ERG risk genotype was underrepresented in ALL with the ETV6-RUNX1 fusion (P < .0005) but enriched in the TCF3-PBX1 subtype (P < .05). Interestingly, ALL cases with germline ERG risk alleles were significantly less likely to have somatic ERG deletion (P < .05). Our results provide novel insights into genetic predisposition to ALL and its contribution to racial disparity in this cancer.
Source: Blood
Authors: Maoxiang Qian, Heng Xu, Virginia Perez-Andreu, Kathryn G. Roberts, Hui Zhang, Wenjian Yang, Shouyue Zhang, Xujie Zhao, Colton Smith, Meenakshi Devidas, Julie M. Gastier-Foster, Elizabeth Raetz, Eric Larsen, Esteban G. Burchard, Naomi Winick, W. Paul Bowman, Paul L. Martin, Michael Borowitz, Brent Wood, Federico Antillon-Klussmann, Ching-Hon Pui, Charles G. Mullighan, William E. Evans, Stephen P. Hunger, Mary V. Relling, Mignon L. Loh, Jun J. Yang
Institutions: St. Jude Children's Research Hospital, Fudan University, Sichuan University, West China Hospital of Sichuan University, State Key Laboratory of Biotherapy, University of Nevada, Reno, Guangzhou Women and Children Medical Center, University of Florida Health, University of Florida, Nationwide Children's Hospital, The Ohio State University, NYU Langone Health, New York University, University of California, San Francisco, The University of Texas Southwestern Medical Center, Cook Children's Medical Center, Duke University, Johns Hopkins Medicine, University of Washington, Children's Hospital of Philadelphia, University of Pennsylvania, UCSF Helen Diller Family Comprehensive Cancer Center
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1104154511, G1504112592, G1600560672, G2554726104, G2688579988, G2901481919, Pharmacogenomics of Childhood Leukemia ALL, Support for Human Specimen Banking in NCI-Sponsored Clinical Trials-(CGB), G386607036, G421865639, Children's Oncology Group Statistics and Data Center, G46020690, G5888954722, PHARMACOGENOMICS OF CHILDHOOD LEUKEMIA (ALL), Cancer Center Support Grant (CCSG), G997771125
OpenAlex ID: W2902073792