A Literature Review and Pooled Case Analysis of Cardiofaciocutaneous Syndrome to Estimate Cancer Risk
medrxiv(2024)
摘要
Background Cardiofaciocutaneous syndrome (CFC) is a rare disorder with multiple congenital anomalies including macrocephaly, failure to thrive, and neurocognitive delay. CFC is part of RASopathy syndromes caused by pathogenic germline variants in BRAF, KRAS, MAP2K1, and MAP2K2. To estimate cancer risk in CFC we conducted a systematic review using case reports and series. Methods We reviewed articles and abstracted CFC cases to form a retrospective cohort based on PRISMA guidelines. Genotype-phenotype (cancer) correlations, standardized incidence ratios (SIR), cumulative incidence and cause-specific hazard rates for cancer and cancer-free in CFC were calculated. Results This study includes 198 publications reporting 690 patients. Only 1.6% (11) had cancer, including acute lymphoblastic leukemia (ALL). Six cancer patients 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 1-2% until age 3 and declined thereafter. Significant SIRs were found for all sites (SIR=4.96) and ALL (SIR=24.23). Conclusions This is the largest investigation of cancer in CFC to date. Cancer risk in the CFC population is elevated but appears limited to earlier childhood. Modest case and cancer numbers could pose limitations to accurately assess cancer risk in CFC and more studies are needed. Systematic Review Registration The review was registered using PROSPERO under the identification tag CRD42023405823(https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405823) Key Words: Cardiofaciocutaneous syndrome, cancer risk, cancer predisposition, cancer genes, BRAF, KRAS, MAP2K1/2, RASopathies
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
The author(s) received no specific funding for this work.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
更多查看译文
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要