SynthesisJournal of the National Cancer Institute2022
Heterozygous BRCA1 and BRCA2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents With Cancer.
Synthesis in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- ERN GENTURIS guidelines on constitutional mismatch repair deficiency diagnosis, genetic counselling, surveillance, quality of life, and clinical management.European journal of human genetics : EJHG · 2024Guideline
- Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Outcomes of germ line testing for children with hematologic malignancies undergoing hematopoietic cell transplantation.Blood advances · 2026Article
- Clinical Impact of Germline Multigene Sequencing in Pediatric Cohorts with a Wide Spectrum of Neoplasms.International journal of molecular sciences · 2026Article
- Prevalence and Clinical Significance of Adult-Onset Cancer Predisposition Variants in Pediatric Oncology.medRxiv : the preprint server for health sciences · 2026Article
- Germline variants in ATM, BRCA2, other cancer predisposition and novel candidate genes are implicated in glioma risk in adult glioma patients with a familial or personal history of tumors.Acta neuropathologica · 2026Article
- Germline variants observed in pediatric cancer patients related to hereditary breast and ovarian cancer in adults.International journal of cancer · 2025Article
- Pediatric Oncology Patients With Germline Pathogenic Variants in Adult-Onset Cancer Predisposition Genes.JCO precision oncology · 2025Article
- Germline Cancer Predisposition Results From the National Cancer Institute-Children's Oncology Group Pediatric MATCH Trial.JCO precision oncology · 2025Article
- The landscape of germline variants in breast and colorectal cancer susceptibility genes in patients with pituitary tumours.Journal of neuro-oncology · 2025Article
- Review
- Constitutional Mismatch Repair Deficiency, the Most Aggressive Cancer Predisposition Syndrome : Clinical Presentation, Surveillance, and Management.Journal of Korean Neurosurgical Society · 2025Article
- Childhood, adolescent, and young adulthood cancer risk in BRCA1 or BRCA2 pathogenic variant carriers.Journal of the National Cancer Institute · 2025Article
- Re-envisioning genetic predisposition to childhood and adolescent cancers.Nature reviews. Cancer · 2025Review
- Update on Recommendations for Cancer Screening and Surveillance in Children with Genomic Instability Disorders.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Adult-Onset Cancer Predisposition Syndromes in Children and Adolescents-To Test or not to Test?Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Germline pathogenic variants in neuroblastoma patients are enriched in BARD1 and predict worse survival.Journal of the National Cancer Institute · 2024Article
- BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma.Journal of the National Cancer Institute · 2024Article
- Research on Rare Diseases in Germany - The cancer predisposition syndrome registry.Journal of health monitoring · 2023Article
- Pathogenic Germline Variants in BRCA1/2 and p53 Identified by Real-world Comprehensive Cancer Genome Profiling Tests in Asian Patients.Cancer research communications · 2023Article
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
Abstract
backgroundGenetic predisposition is has been identified as a cause of cancer, yet little is known about the role of adult cancer predisposition syndromes in childhood cancer. We examined the extent to which heterozygous pathogenic germline variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, MSH2, MSH6, MLH1, and PMS2 contribute to cancer risk in children and adolescents.
methodsWe conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer. ClinVar pathogenic or likely pathogenic variants (PVs) in genes of interest were compared with 2 control groups. Results were validated in a cohort of mainly European patients and controls. We employed the Proxy External Controls Association Test to account for different pipelines.
resultsAmong 3975 children and adolescents with cancer, statistically significant associations with cancer risk were observed for PVs in BRCA1 and 2 (26 PVs vs 63 PVs among 27 501 controls, odds ratio = 2.78, 95% confidence interval = 1.69 to 4.45; P < .001) and mismatch repair genes (19 PVs vs 14 PVs among 27 501 controls, odds ratio = 7.33, 95% confidence interval = 3.64 to 14.82; P <.001). Associations were seen in brain and other solid tumors but not in hematologic neoplasms. We confirmed similar findings in 1664 pediatric cancer patients primarily of European descent.
conclusionThese data suggest that heterozygous PVs in BRCA1 and 2 and mismatch repair genes contribute with reduced penetrance to cancer risk in children and adolescents. No changes to predictive genetic testing and surveillance recommendations are required.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.