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. STUDY DESIGN: 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. CONCLUSION: NOS3 variants modulate externalizing problems individual trajectories, likely in relationship with glucocorticoid exposure.
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. STUDY DESIGN: Behavioral problems in pediatric acute lymphoblastic leukemiapatients (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. CONCLUSION:NOS3 variants modulate externalizing problems individual trajectories, likely in relationship with glucocorticoid exposure.
Authors: Eric J Chow; Kirsten K Ness; Gregory T Armstrong; Nickhill Bhakta; Jennifer M Yeh; Smita Bhatia; Wendy Landier; Louis S Constine; Melissa M Hudson; Paul C Nathan Journal: Semin Oncol Date: 2020-03-04 Impact factor: 4.929
Authors: M Krajinovic; J Elbared; S Drouin; L Bertout; A Rezgui; M Ansari; M-J Raboisson; S E Lipshultz; L B Silverman; S E Sallan; D S Neuberg; J L Kutok; C Laverdière; D Sinnett; G Andelfinger Journal: Pharmacogenomics J Date: 2015-09-08 Impact factor: 3.550