N-PhenoGENICS: Neurocognitive-Phenome, Genome, Epigenome and Nutriome In Childhood Leukemia Survivors

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

Inclusion Criteria:

• Past diagnosis of acute lymphoblastic leukemia
• 8 years : 0 months - 20 years : 11 months old at the time of their study visit
• At least 2 years : 0 months from the last treatment for acute lymphoblastic leukemia at the time of their study visit
• Continuous complete remission and undergone no bone marrow transplantation or cranial radiation therapy
• Fluent in English (a subject and one parent) for test completion
• Signed informed consent

Exclusion Criteria:

• Inability to complete the phenotyping tests
• Down Syndrome diagnosis