Fumarate hydratase variant prevalence and manifestations among individuals receiving germline testing

Autor: Eric Lu, Shantao Li, Kathryn E. Hatchell, Heather R. Christofk, Blake R. Wilde, Brian Shuch, Keith Nykamp, Shirin Zavoshi, Liying Zhang, Sarah M. Nielsen, Karen Ouyang, Edward D. Esplin, Paul C. Boutros
Rok vydání: 2021
Předmět:
Oncology
Cancer Research
Kidney Disease
Skin Neoplasms
Fumarase deficiency
urologic and male genital diseases
Germline
Fumarate Hydratase
Renal cell carcinoma
Prevalence
kidney neoplasms
2.1 Biological and endogenous factors
Aetiology
Cancer
education.field_of_study
medicine.diagnostic_test
Penetrance
Kidney Neoplasms
Hereditary
Uterine Neoplasms
Public Health and Health Services
Female
hereditary leiomyomatosis and renal cell cancer
fumarate hydratase
medicine.medical_specialty
Oncology and Carcinogenesis
Population
Article
genetic testing
Cancer syndrome
Clinical Research
Neoplastic Syndromes
Hereditary
Leiomyomatosis
Internal medicine
Genetics
medicine
Humans
Neoplastic Syndromes
Oncology & Carcinogenesis
education
Carcinoma
Renal Cell
Germ-Line Mutation
Genetic testing
business.industry
Carcinoma
Renal Cell
medicine.disease
Germ Cells
business
Zdroj: Cancer
Cancer, vol 128, iss 4
ISSN: 1097-0142
0008-543X
DOI: 10.1002/cncr.33997
Popis: BackgroundGermline variants in fumarate hydratase (FH) are associated with autosomal dominant (AD) hereditary leiomyomatosis and renal cell cancer (HLRCC) and autosomal recessive (AR) fumarase deficiency (FMRD). The prevalence and cancer penetrance across different FH variants remain unclear.MethodsA database containing 120,061 records from individuals undergoing cancer germline testing was obtained. FH variants were classified into 3 categories: AD HLRCC variants, AR FMRD variants, and variants of unknown significance (VUSs). Individuals with variants from these categories were compared with those with negative genetic testing.ResultsFH variants were detected in 1.3% of individuals (AD HLRCC, 0.3%; AR FMRD, 0.4%; VUS, 0.6%). The rate of AD HLRCC variants discovered among reportedly asymptomatic individuals without a clear indication for HLRCC testing was 1 in 2668 (0.04%). In comparison with those with negative genetic testing, the renal cell carcinoma (RCC) prevalence was elevated with AD HLRCC variants (17.0% vs 4.5%; P 
Databáze: OpenAIRE
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