Childhood Leukemia Survivors Clinical Trial
Official title:
N-PhenoGENICS: Neurocognitive-Phenome, Genome, Epigenome and Nutriome In Childhood Leukemia Survivors
To find possible therapeutic targets to help prevent long-term brain and behavioural side effects in survivors of childhood leukemia that may have been caused by chemotherapy (Treatment-Related late Adverse Neuro-Cognitive Effects: TRANCE). The study hypothesis is that genetic variations of the elements in the folate-related cycles and methotrexate disposition networks are associated with the deficit phenotype (TRANCE) of childhood leukemia survivors.
Hypothesis Genetic variants of the elements in the folate-related cycles and methotrexate
disposition networks are associated with the TRANCE phenotype of childhood leukemia
survivors.
Objectives
1. To identify TRANCE phenotypes of the childhood leukemia survivors.
2. To characterize the folate and vitamin B12 levels of these children
3. To identify DNA methylation patterns associated with TRANCE trait in the leukemia
survivors
4. To identify SNPs associated with the TRANCE trait in the leukemia survivors.
5. To identify the "deficit genotype" associated only with the TRANCE leukemia survivors,
but not with general population children who show developmental phenotypes similar to
TRANCE: TRANCE-unique deficit variant
6. To replicate the association between the TRANCE-unique deficit variants and the TRANCE
trait in a population of childhood leukemia survivors.
7. To evaluate the importance of rare genetic variants in the TRANCE trait in the leukemia
survivors.
Study design: A case-control study of leukemia survivors
Analyses
1. Leukemia survivors will be characterized by their status of neurocognitive function, and
categorized into the Deficit case and the non-deficit Control case.
2. They will be also characterized by the following attributes
1. Pathway-based genetic variant status (folate and PK-related genes)
2. Folate and vitamin B12 status
3. Epigenetic markers
3. Comparative analyses between neuro-cognitiive deficit phenotype (TRANCE) and Control on
those parameters
;