title: Association of Genetic Variants in ARID5B, IKZF1 and CEBPE with Risk of Childhood de novo B-Lineage Acute Lymphoblastic Leukemia in India.
abstract: BACKGROUND
  Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous genetic disease and its etiology remains poorly understood. Recent genome wide association and replication studies have highlighted specic polymorphisms contributing to childhood ALL predispositions mostly in European populations. It is unclear if these observations generalize to other populations with a lower incidence of ALL. The current case-control study evaluated variants in ARID5B (rs7089424, rs10821936), IKZF1 (rs4132601) and CEBPE (rs2239633) genes, which appear most significantly associated with risk of developing childhood B-lineage ALL.
  
  
  METHODS
  Using TaqMan assays, genotyping was conducted for 162 de novo B-lineage ALL cases and 150 unrelated healthy controls in India. Appropriate statistical methods were applied.
  
  
  RESULTS
  Genotypic and allelic frequencies differed significantly between cases and controls at IKZF1-rs4132601 (p=0.039, p=0.015) and ARID5B-rs10821936 (p=0.028, p=0.026). Both rs10821936 (p=0.019; OR 0.67; 95% CI=0.47-0.94) and rs4132601 (p=0.018; OR 0.67; 95%CI 0.48-0.94) were associated with reduced disease risk. Moreover, gender- analysis revealed male-specific risk associations for rs10821936 (p=0.041 CT+CC) and rs4132601 (p=0.005 G allele). Further, ARID5B-rs7089424 and CEBPE-rs2239633 showed a trend towards decreased disease risk but without significance (p=0.073; p=0.73).
  
  
  CONCLUSIONS
  Our findings provide the rst evidence that SNPs ARID5B- rs10821936 and IKZF1-rs4132601 are associated with decreased B-lineage ALL susceptibility in Indian children. Understanding the effects of these variants in different ethnic groups is crucial as they may confer different risk of ALL within different populations.
authors.affiliation: Mentor-Molecular Pathology and Clinical Research Services, Research and Development, Goregaon, Mumbai, India E-mail : brdas@srl.in.
authors.forename: Prerana
authors.initials: P
authors.lastname: Bhandari
authors.forename: Firoz
authors.initials: F
authors.lastname: Ahmad
authors.forename: Swarna
authors.initials: S
authors.lastname: Mandava
authors.forename: Bibhu Ranjan
authors.initials: BR
authors.lastname: Das
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C503805:ARID5B protein, human; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; C070790:CEBPE protein, human; D051740:Ikaros Transcription Factor