ArticlePloS one2019
Influence of genetic factors on long-term treatment related neurocognitive complications, and on anxiety and depression in survivors of childhood acute lymphoblastic leukemia: The Petale study.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Monitoring Neurocognitive Functioning After Pediatric Cellular Therapy or Hematopoietic Cell Transplant: Guidelines From the COG Neurocognition in Cellular Therapies Task Force.Transplantation and cellular therapy · 2022Guideline
- Disparities in anxiety and related factors among Chinese older adults across different aged-care models: a comparison of two cross-sectional studies.BMC geriatrics · 2025Article
- Uncovering possible silent acquired long QT syndrome using exercise stress testing in long-term pediatric acute lymphoblastic leukemia survivors.International journal of cancer · 2025Article
- Genetic Factors and Long-term Treatment-Related Neurocognitive Deficits, Anxiety, and Depression in Childhood Leukemia Survivors: An Exome-Wide Association Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims.International journal of molecular sciences · 2022Article
- Article
- Genetic factors in treatment-related cardiovascular complications in survivors of childhood acute lymphoblastic leukemia.Pharmacogenomics · 2021Article
- National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia: the ALL-STAR study protocol.BMJ open · 2021Article
- HLA alleles associated with asparaginase hypersensitivity in childhood ALL: a report from the DFCI Consortium.Pharmacogenomics · 2020Article
- Role of Autophagy and Apoptosis in Acute Lymphoblastic Leukemia.Cancer control : journal of the Moffitt Cancer CenterReview
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18 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundA substantial number of survivors of childhood acute lymphoblastic leukemia suffer from treatment-related late adverse effects including neurocognitive impairment. While multiple studies have described neurocognitive outcomes in childhood acute lymphoblastic leukemia (ALL) survivors, relatively few have investigated their association with individual genetic constitution.
methodsTo further address this issue, genetic variants located in 99 genes relevant to the effects of anticancer drugs and in 360 genes implicated in nervous system function and predicted to affect protein function, were pooled from whole exome sequencing data of childhood ALL survivors (PETALE cohort) and analyzed for an association with neurocognitive complications, as well as with anxiety and depression. Variants that sustained correction for multiple testing were genotyped in entire cohort (n = 236) and analyzed with same outcomes.
resultsCommon variants in MTR, PPARA, ABCC3, CALML5, CACNB2 and PCDHB10 genes were associated with deficits in neurocognitive tests performance, whereas a variant in SLCO1B1 and EPHA5 genes was associated with anxiety and depression. Majority of associations were modulated by intensity of treatment. Associated variants were further analyzed in an independent SJLIFE cohort of 545 ALL survivors. Two variants, rs1805087 in methionine synthase, MTR and rs58225473 in voltage-dependent calcium channel protein encoding gene, CACNB2 are of particular interest, since associations of borderline significance were found in replication cohort and remain significant in combined discovery and replication groups (OR = 1.5, 95% CI, 1-2.3; p = 0.04 and; OR = 3.7, 95% CI, 1.25-11; p = 0.01, respectively). Variant rs4149056 in SLCO1B1 gene also deserves further attention since previously shown to affect methotrexate clearance and short-term toxicity in ALL patients.
conclusionsCurrent findings can help understanding of the influence of genetic component on long-term neurocognitive impairment. Further studies are needed to confirm whether identified variants may be useful in identifying survivors at increased risk of these complications.
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