학술논문
Update of penetrance estimates in Birt-Hogg-Dubé syndrome.
Document Type
Academic Journal
Author
Bruinsma FJ; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia fiona.bruinsma@cancervic.org.au.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria, Australia.; Dowty JG; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Victoria, Australia.; Win AK; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, Victoria, Australia.; Goddard LC; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Agrawal P; Department of Radiology, University of Michigan Michigan Medicine, Ann Arbor, Michigan, USA.; Attina' D; Department of Radiology, Azienda Ospedaliero-Universitaria di Bologna IRCCS, Bologna, Italy.; Bissada N; Department of Urology, Baylor College of Medicine, Houston, Texas, USA.; De Luise M; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; Eisen DB; Department of Dermatology, University of California Davis, Davis, California, USA.; Furuya M; Pathology Centre, Genetic Lab Co., Ltd, Sapporo, Japan.; BHD-Net Japan, Hokkaido, Japan.; Gasparre G; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; Genuardi M; Department of Life Sciences and Public Health, Universita' Cattolica di Sacro Cuore, Roma, Italy.; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.; Gerdes AM; Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Hansen TVO; Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Kobenhavn, Denmark.; Houweling AC; Department of Human Genetics, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Johannesma PC; Department of Pulmonary Disease, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; Lencastre A; Servico de Dermatologia, Hospital de Santo Antonio dos Capuchos, Lisboa, Portugal.; Lim D; Clinical Genetic Unit, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.; Lindor NM; Mayo Clinic, Phoenix, Arizona, USA.; Luzzi V; Department of Experimental and Clinical Medicine, Interventional Pulmonology Unit, Careggi University Hospital, Florence, Italy.; Lynch M; St Vincent's University Hospital, Dublin, Ireland.; Maffé A; SS Genetica e Biologia Molecolare ASO.S, Cuneo, Italy.; Menko FH; Family Cancer Clinic, Antoni van Leeuwenhoek Hospital, the Netherlands Cancer Institute, Amsterdam, Netherlands.; Michels G; Department of Acute and Emergency Care, St Antonius Hospital Eschweiler, Eschweiler, Germany.; Pulido JS; Mayo Clinic, Rochester, Minnesota, USA.; Department of Translational Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, USA.; Ryu JH; Mayo Clinic, Rochester, Minnesota, USA.; Sattler EC; Department of Dermatology and Alleregy, LMU Munich, Munich, Germany.; Steinlein OK; Department of Genetics, University Hospital, LMU Munich, Munich, Germany.; Tomassetti S; Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy.; Tucker K; Hereditary Cancer Centre, Prince of Wales Hospital, Sydney, New South Wales, Australia.; Division of Medicine, University of New South Wales, Sydney, New South Wales, Australia.; Turchetti D; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.; van de Beek I; Department of Human Genetics, Amsterdam UCM, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; van Riel L; Department of Human Genetics, Amsterdam UCM, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.; van Steensel M; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.; Zenone T; Department of Internal Medicine, Centre Hospitalier de Valence, Valence, France.; Zompatori M; IRCCS Multimedica Group, San Giuseppe Hospital, Milan, Italy.; Walsh J; Centre of Research Excellence in Pulmonary Fibrosis, The University of Sydney, Sydney, New South Wales, Australia.; Bondavalli D; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Maher ER; Birmingham Women's and Children's NHS Foundation Trust, Clinical Genetics Unit, West Midlands Regional Genetics Services, Birmingham, UK.; Department of Medical Genetics, University of Cambridge, Cambridge, UK.; Winship IM; Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
Source
Publisher: British Medical Association Country of Publication: England NLM ID: 2985087R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-6244 (Electronic) Linking ISSN: 00222593 NLM ISO Abbreviation: J Med Genet Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series.
Methods: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN . Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants.
Results: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers.
Conclusions: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Methods: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN . Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants.
Results: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers.
Conclusions: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)