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September 1, 2025JCO Precision Oncology

Rare Variants Associated With Pediatric Cancer Treatment–Related Second Malignant Neoplasm Risk

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Authors

CDClaire DucosAutorité de Sûreté NucléaireBFBrice FresneauInsermFRFilippo RosselliUniversité Paris-Saclay

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Overview

Nested case-control study finds rare genetic variants increase second malignant neoplasm risk in childhood cancer survivors, suggesting genetic susceptibility to post-treatment cancers.

Key Points

  • Rare genetic variants in RNASEL and APOBEC3F pathways significantly elevate second malignant neoplasms risk in pediatric cancer survivors treated with radiation therapy.
  • Carriers of RNASEL variants showed an odds ratio of 5.43 for second malignant neoplasms, while FANCM alterations conferred a 4.65-fold increased risk for breast malignancy.
  • Nested case-control study of whole-exome sequencing across 450 survivors and logistic regression analysis highlight actionable genetic risks, though external replication is needed.

Cite This Study

Ducos et al. (2025) studied this question.

synapsesocial.com/papers/68e55b4ce2b3180350ef873ehttps://doi.org/10.1200/po-24-00668
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Uncovering genetic susceptibility to second malignant neoplasms in children and young adults: Findings from a tertiary oncology center in a resource-limited setting.2026
  2. 2Germline variants in patients developing second malignant neoplasms after therapy for pediatric acute lymphoblastic leukemia—a case-control study2024 · 8 citations
  3. 3Abstract 6155: Germline variants in cancer susceptibility genes and subsequent neoplasm risks after childhood cancer: A pooled analysis of two large-scale cohorts2024
  4. 4Temporal Trends of Subsequent Malignant Neoplasms in Childhood Cancer Survivors and the Impact of Treatment Changes: A DCCSS-LATER Study2026
  5. 5Subsequent Malignant Neoplasms in Childhood Cancer Survivors: Identifying Risks and Screening Recommendations.2026