Jazmyn Bess, Toniya Brown, Sonia Bhala, Anaqa Faizer, Muzzammil Ahmadzada, Alicia A Livinski, Alex Pemov, Jung Kim, Philip S Rosenberg, Gina M Ney, Douglas R Stewart
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引用次数: 0
Abstract
Purpose: We quantified cancer risk in cardiofaciocutaneous syndrome (CFC), a rare RASopathy.
Methods: From a comprehensive search, we reviewed articles from five 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 (SIR) 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.
Results: This study included 198 publications reporting 690 individuals. Only 1.6% (11) had cancer, including acute lymphoblastic leukemia (ALL). 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 1-2% 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 was elevated but appears to be limited to younger than age three. However, modest case and cancer numbers limit accurate assessments of cancer risk in CFC and more studies are needed.
期刊介绍:
Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health.
GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.