title: Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia.
abstract: BACKGROUND
  Acute leukemias of childhood are a heterogeneous group of malignancies characterized by cytogenetic abnormalities, such as translocations and changes in ploidy. These abnormalities may be influenced by altered DNA repair and cell cycle control processes.
  
  
  METHODS
  We examined the association between childhood acute lymphoblastic leukemia (ALL) and 32 genes in DNA repair and cell cycle pathways using a haplotype-based approach, among 377 childhood ALL cases and 448 controls enrolled during 1995-2002.
  
  
  RESULTS
  We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total ALL, while haplotypes in NBN and XRCC4, and CDKN2A were associated with structural and numerical change subtypes, respectively. In addition, we observed statistically significant interaction between exposure to 3 or more diagnostic X-rays and haplotypes of XRCC4 on risk of structural abnormality-positive childhood ALL.
  
  
  CONCLUSIONS
  These results support a role of altered DNA repair and cell cycle processes in the risk of childhood ALL, and show that this genetic susceptibility can differ by cytogenetic subtype and may be modified by exposure to ionizing radiation. To our knowledge, our study is the first to broadly examine the DNA repair and cell cycle pathways using a haplotype approach in conjunction with X-ray exposures in childhood ALL risk. If confirmed, future studies are needed to identify specific functional SNPs in the regions of interest identified in this analysis.
authors: Division of Epidemiology, School of Public Health, University of California-Berkeley, 1995 University Avenue, Berkeley, CA 94704, USA. anandc@berkeley.edu
authors: Anand P
authors: AP
authors: Chokkalingam
authors: Karen
authors: K
authors: Bartley
authors: Joseph L
authors: JL
authors: Wiemels
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: Jeffrey S
authors: JS
authors: Chang
authors: Stacy R
authors: SR
authors: Month
authors: John K
authors: JK
authors: Wiencke
authors: Patricia A
authors: PA
authors: Buffler
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D004260:DNA Repair / Q000235:genetics*; D018816:Genes, cdc / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012307:Risk Factors; D014965:X-Rays / Q000009:adverse effects*