title: Role of NOS3 DNA variants in externalizing behavioral problems observed in childhood leukemia survivors.
abstract: OBJECTIVE
  Neuropsychological problems occurrence varies among childhood cancer survivors, and associated risk factors have not been fully deciphered. We wanted to study the role of genetic variants in behavioral problems in this population.
  
  
  METHODS
  Behavioral problems in pediatric acute lymphoblastic leukemia patients (n=138) were investigated longitudinally, using the Child Behavior Checklist questionnaire and multilevel statistical modeling. Thirty-four candidate polymorphisms, related to anticancer drug effects, were investigated.
  
  
  RESULTS
  NOS3 gene functional polymorphisms showed significant association: patients homozygous for the minor allele at investigated loci showed decreased externalizing behavioral problems scores over time (t tests: T-786C n=69, P=0.003; G894T n=71, P=0.065). The effect was even more pronounced for individuals that are homozygous for the -786C844T haplotype (t test, n=69, P<0.001) and results were supported by multilevel modeling analyses (P<0.001). No such association was observed for internalizing behavioral problems.
  
  
  CONCLUSIONS
  NOS3 variants modulate externalizing problems individual trajectories, likely in relationship with glucocorticoid exposure.
authors.affiliation: Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Marcoux
authors.forename: Philippe
authors.initials: P
authors.lastname: Robaey
authors.forename: Annabel
authors.initials: A
authors.lastname: Gahier
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Labuda
authors.forename: Julie
authors.initials: J
authors.lastname: Rousseau
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
authors.forename: Albert
authors.initials: A
authors.lastname: Moghrabi
authors.forename: Caroline
authors.initials: C
authors.lastname: Laverdière
authors.forename: Maja
authors.initials: M
authors.lastname: Krajinovic
mesh_terms: D000293:Adolescent; D002648:Child; D002653:Child Behavior Disorders / Q000139:chemically induced / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics*; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics / Q000523:psychology*; D011795:Surveys and Questionnaires; D017741:Survivors / Q000523:psychology
chemical_list: D004273:DNA, Neoplasm; D005938:Glucocorticoids; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III