Evidence map›Paper›PMID 40196938›Full record

ReviewGenetics in medicine : official journal of the American College of Medical Genetics2025

A literature review and pooled case analysis of cardiofaciocutaneous syndrome to estimate cancer risk.

Jazmyn Bess, Toniya Brown, Sonia Bhala, Anaqa Faizer, Muzzammil Ahmadzada, Alicia A Livinski, Alex Pemov, Jung Kim, Philip S Rosenberg, Gina M Ney and 1 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jazmyn BessClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Toniya BrownClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Sonia BhalaClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD; Department of Obstetrics and Gynecology, Robert Wood Johnson Barnabas Health at Monmouth Medical Center, Long Branch, NJ.
Anaqa FaizerClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Muzzammil AhmadzadaClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD; Stanford University School of Medicine, Stanford, CA.
Alicia A LivinskiNIH Library, Office of Research Services, Office of the Director, National Institutes of Health, Bethesda, MD.
Alex PemovClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Jung KimClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Philip S RosenbergBiostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Gina M NeyClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD.
Douglas R StewartClinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. Electronic address: drstewart@mail.nih.gov.

Funding

Genetic Modifiers of Cancer RiskZIACP010142 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI MIRABELLO, LISA · 2009 to 2025
$17.1M
Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA CP010142
6 · The paper itself

Abstract

purposeWe quantified cancer risk in cardiofaciocutaneous syndrome (CFC), a rare RASopathy.

methodsFrom a comprehensive search, we reviewed articles from 5 databases and abstracted CFC cases with a clinical and/or molecular diagnosis to form a retrospective cohort. We collected information on BRAF, KRAS, MAP2K1, and MAP2K2 genetic variants when available. Genotype-phenotype (cancer) correlations, standardized incidence ratios (SIRs) with age stratification, cumulative incidence and cause-specific hazard rates for cancer and cancer-free in CFC were calculated. A sensitivity analysis with molecular diagnoses only was also performed.

resultsThis study included 198 publications reporting 690 individuals. Only 1.6% (11) had cancer, including acute lymphoblastic leukemia. Six individuals had cancer and harbored pathogenic variants within BRAF, MAP2K1, and MAP2K2. Cumulative incidence by age 10 was 5% for cancer or cancer-free death. Hazard Ratio (death) was 1% to 2% until age 3 and declined thereafter. Significant SIRs were found for all sites (SIR = 4.96) and acute lymphoblastic leukemia (SIR = 24.23).

conclusionTo our knowledge, this is the largest investigation of cancer in CFC to date. Cancer risk in the CFC population was elevated but appears to be limited to younger than age 3. However, modest case and cancer numbers limit accurate assessments of cancer risk in CFC and more studies are needed.

Indexed as

Ectodermal DysplasiaFailure to ThriveHeart Defects, CongenitalNeoplasmsAdolescentAdultChildChild, PreschoolFaciesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansIncidenceInfantMaleBRAF protein, humanKRAS protein, humanMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2Proto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Cancer riskCardiofaciocutaneous syndromeGermline variantsRASopathies

Identifiers

PMID40196938
PMCPMC12229772

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Registered trials

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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.