In:
Pediatric Blood & Cancer, Wiley, Vol. 70, No. 9 ( 2023-09)
Abstract:
Osteosarcoma (OS) is a rare pediatric cancer for which therapeutic approaches, including chemotherapy and surgery, show a wide interindividual variability in patient response, both in terms of adverse events and therapy efficacy. There is growing evidence that this individual variable response to therapies is also influenced by inherited genetic variations. However, the results obtained to date in these pediatric cancers have been contradictory and often lack validation in independent series. Additionally, these studies frequently focused only on a limited number of polymorphisms in candidate genes. Methods In order to identify germline coding variations associated with individual differences in adverse events occurrence in pediatric patients affected by localized OS, we carried out an exome‐wide association study in 24 OS patients treated with methotrexate, cisplatin, and doxorubicin, using the SNP‐Set (Sequence) Kernel Association Test (SKAT), optimized for small sample size. Results Gene sets significantly associated (FDR 〈 .05) with neutropenia and hepatotoxicity induced by methotrexate were identified. Some of the identified genes map in loci previously associated with similar phenotypes (e.g., leukocyte count, alkaline phosphatase levels). Conclusion Further studies in larger series and with functional characterization of the identified associations are needed; nonetheless, this pilot study prompts the relevance of broadly investigating variants along the whole genome, to identify new potential pharmacogenes, beyond drug metabolism, transport, and receptor candidate genes.
Type of Medium:
Online Resource
ISSN:
1545-5009
,
1545-5017
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2130978-4
