Association of genetic variation in Emphasis Type

Authors: LingI Hsu Anand P Chokkalingam Farren B S Briggs Kyle Walsh Vonda Crouse Cecilia Fu Catherine Metayer Joseph L Wiemels Lisa F Barcellos Patricia A Buffler

Publish Date: 2015/03/12

Volume: 26, Issue: 4, Pages: 609-619

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Abstract

Genomewide association studies focusing on Europeanancestry populations have identified ALL risk loci on IKZF1 ARID5B and CEBPE To capture the impacts of these genes on ALL risk in the California Hispanic population we comprehensively assessed the variation within the genes and further assessed the joint effects between the genetic variation and surrogates for earlylife infections the presence of older siblings daycare attendance and ear infectionsGenotypic data for 323 Hispanic ALL cases and 454 controls from the California Childhood Leukemia Study were generated using Illumina OmniExpress v1 platform Logistic regression assuming a logadditive model estimated odds ratios OR associated with each SNP adjusted for age sex and the first five principal components In addition we examined potential interactions between six ALL risk alleles and surrogates for earlylife infections using logistic regression models that included an interaction termSignificant associations between genotypes at IKZF1 ARID5B and CEBPE and ALL risk were identified rs7780012 OR 050 95  confidence interval CI 035–071 p = 0004 rs7089424 OR 212 95  CI 170–265 p = 116 × 10−9 rs4982731 OR 169 95  CI 137–208 p = 235 × 10−6 respectively Evidence for multiplicative interactions between genetic variants and surrogates for earlylife infections with ALL risk was not observedConsistent with findings in nonHispanic White population our study showed that variants within IKZF1 ARID5B and CEBPE were associated with increased ALL risk and the effects for ARID5B and CEBPE were most prominent in the highhyperdiploid ALL subtype in the California Hispanic population Results implicate the ARID5B CEBPE and IKZF1 genes in the pathogenesis of childhood ALLWe thank the participated hospitals and clinical collaborators including University of California Davis Medical Center Dr Jonathan Ducore University of California San Francisco Dr Mignon Loh and Dr Katherine Matthay Children’s Hospital of Central California Dr Vonda Crouse Lucile Packard Children’s Hospital Dr Gary Dahl Children’s Hospital Oakland Dr James Feusner Kaiser Permanente Sacramento Dr Vincent Kiley Kaiser Permanente Santa Clara Dr Carolyn Russo and Dr Alan Wong Kaiser Permanente San Francisco Dr Kenneth Leung Children’s Hospital of Los Angeles Dr Cecilia Fu and Kaiser Permanente Oakland Dr Stacy Month We also acknowledge our collaborators at the Northern California Cancer Center and the entire California Childhood Leukemia Study staff for their effort and dedication This study was supported by grants from the National Institute of Environmental Health Sciences PS42 ES04705 and R01 ES09137 the National Cancer Institute R25CA112355 and Children with Cancer United Kingdom

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