title: Genetic polymorphisms in adaptive immunity genes and childhood acute lymphoblastic leukemia.
abstract: BACKGROUND
  Childhood acute lymphoblastic leukemia (ALL) has been hypothesized to have an infection- and immune-related etiology. The lack of immune priming in early childhood may result in abnormal immune responses to infections later in life and increase ALL risk.
  
  
  METHODS
  The current analyses examined the association between childhood ALL and 208 single-nucleotide polymorphisms (SNP) of 29 adaptive immune function genes among 377 ALL cases and 448 healthy controls. Single SNPs were analyzed with a log-additive approach using logistic regression models adjusted for sex, age, Hispanic ethnicity, and race. Sliding window haplotype analyses were done with haplotypes consisting of 2 to 6 SNPs.
  
  
  RESULTS
  Of the 208 SNPs, only rs583911 of IL12A, which encodes a critical modulator of T-cell development, remained significant after accounting for multiple testing (odds ratio for each copy of the variant G allele, 1.52; 95% confidence interval, 1.25-1.85; P = 2.9 x 10(-5)). This increased risk was stronger among firstborn children of all ethnicities and among non-Hispanic children with less day care attendance, consistent with the hypothesis about the role of early immune modulation in the development of childhood ALL. Haplotype analyses identified additional regions of CD28, FCGR2, GATA3, IL2RA, STAT4, and STAT6 associated with childhood ALL.
  
  
  CONCLUSIONS
  Polymorphisms of genes on the adaptive immunity pathway are associated with childhood ALL risk.
  
  
  CONCLUSIONS
  Results of this study support an immune-related etiology of childhood ALL. Further confirmation is required to detect functional variants in the significant genomic regions identified in this study, in particular for IL12A.
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. jeffreychang@nhri.org.tw
authors: Jeffrey S
authors: JS
authors: Chang
authors: Joseph L
authors: JL
authors: Wiemels
authors: Anand P
authors: AP
authors: Chokkalingam
authors: Catherine
authors: C
authors: Metayer
authors: Lisa F
authors: LF
authors: Barcellos
authors: Helen M
authors: HM
authors: Hansen
authors: Melinda C
authors: MC
authors: Aldrich
authors: Neela
authors: N
authors: Guha
authors: Kevin Y
authors: KY
authors: Urayama
authors: Ghislaine
authors: G
authors: Scélo
authors: Janet
authors: J
authors: Green
authors: Suzanne L
authors: SL
authors: May
authors: Vincent A
authors: VA
authors: Kiley
authors: John K
authors: JK
authors: Wiencke
authors: Patricia A
authors: PA
authors: Buffler
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology*