MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia

Blood. 2011 Feb 3;117(5):1633-40. doi: 10.1182/blood-2010-08-301598. Epub 2010 Nov 8.

Abstract

A role for specific human leukocyte antigen (HLA) variants in the etiology of childhood acute lymphoblastic leukemia (ALL) has been extensively studied over the last 30 years, but no unambiguous association has been identified. To comprehensively study the relationship between genetic variation within the 4.5 Mb major histocompatibility complex genomic region and precursor B-cell (BCP) ALL risk, we analyzed 1075 observed and 8176 imputed single nucleotide polymorphisms and their related haplotypes in 824 BCP-ALL cases and 4737 controls. Using these genotypes we also imputed both common and rare alleles at class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1, HLA-DQA1, and HLA-DQB1) HLA loci. Overall, we found no statistically significant association between variants and BCP-ALL risk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes / genetics*
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II