Polygenic Risk and Chemotherapy-Related Subsequent Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study Report.
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
ISSN: 1527-7755
Titre abrégé: J Clin Oncol
Pays: United States
ID NLM: 8309333
Informations de publication
Date de publication:
20 09 2023
20 09 2023
Historique:
pmc-release:
20
09
2024
medline:
18
9
2023
pubmed:
17
7
2023
entrez:
17
7
2023
Statut:
ppublish
Résumé
Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases. SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS quintiles was estimated, along with hazard ratios (HRs) from proportional hazards models. A total of 1,594 survivors developed SMNs, with basal cell carcinomas (n = 822), breast cancers (n = 235), and thyroid cancers (n = 221) being the most frequent. Although SMN risk associations with the PRS were extremely modest in RT-exposed EUR survivors (HR, 1.22; A pleiotropic cancer PRS has strong potential for improving SMN clinical risk stratification among nonirradiated survivors treated with specific chemotherapies. A polygenic risk screening approach may be a valuable complement to an early screening strategy on the basis of treatments and rare cancer-susceptibility mutations.
Identifiants
pubmed: 37459583
doi: 10.1200/JCO.23.00428
pmc: PMC10522108
doi:
Substances chimiques
Podophyllotoxin
L36H50F353
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4381-4393Subventions
Organisme : NCI NIH HHS
ID : U24 CA055727
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA261833
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA195547
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216354
Pays : United States
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