Your browser doesn't support javascript.
loading
Population-based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high-grade serous ovarian cancer.
Song, Honglin; Dicks, Ed M; Tyrer, Jonathan; Intermaggio, Maria; Chenevix-Trench, Georgia; Bowtell, David D; Traficante, Nadia; Group, Aocs; Brenton, James; Goranova, Teodora; Hosking, Karen; Piskorz, Anna; van Oudenhove, Elke; Doherty, Jen; Harris, Holly R; Rossing, Mary Anne; Duerst, Matthias; Dork, Thilo; Bogdanova, Natalia V; Modugno, Francesmary; Moysich, Kirsten; Odunsi, Kunle; Ness, Roberta; Karlan, Beth Y; Lester, Jenny; Jensen, Allan; Krüger Kjaer, Susanne; Høgdall, Estrid; Campbell, Ian G; Lázaro, Conxi; Pujara, Miguel Angel; Cunningham, Julie; Vierkant, Robert; Winham, Stacey J; Hildebrandt, Michelle; Huff, Chad; Li, Donghui; Wu, Xifeng; Yu, Yao; Permuth, Jennifer B; Levine, Douglas A; Schildkraut, Joellen M; Riggan, Marjorie J; Berchuck, Andrew; Webb, Penelope M; Group, Opal Study; Cybulski, Cezary; Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan.
Afiliação
  • Song H; Department of Oncology, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Dicks EM; Department of Oncology, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Tyrer J; Department of Oncology, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Intermaggio M; School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
  • Chenevix-Trench G; Cancer Genetics, Queensland Institute of Medical Research-QIMR, Herston, Queensland, Australia.
  • Bowtell DD; Cancer Genomics and Genetics and Women's Cancer Programs, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Traficante N; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
  • Group A; QIMR Berghofer Department of Genetics and Computational Biology, Herston, Queensland, Australia.
  • Brenton J; Department of Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Goranova T; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Hosking K; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Piskorz A; Department of Oncology, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • van Oudenhove E; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, Cambridgeshire, UK.
  • Doherty J; Laura and Isaac Perlmutter Cancer Center, New York University, New York, New York, USA.
  • Harris HR; Huntsman Institute, University of Utah, Salt Lake City, Utah, USA.
  • Rossing MA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Duerst M; Department of Epidemiology, University of Washington, Seattle, Washington, USA.
  • Dork T; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  • Bogdanova NV; Department of Epidemiology, University of Washington, Seattle, Washington, USA.
  • Modugno F; Department of Gynaecology, Jena University Hospital, Friedrich Schiller University Jena, Jena, Thüringen, Germany.
  • Moysich K; Gynaecology Research Unit, Hannover Medical School, Hannover, Niedersachsen, Germany.
  • Odunsi K; Department of Radiation Oncology, Hannover Medical School, Hannover, Niedersachsen, Germany.
  • Ness R; Department of Gynaecology, NN Alexandrov National Cancer Centre, Minsk, Minsk, Belarus.
  • Karlan BY; Womens Cancer Research Center, Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA.
  • Lester J; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Jensen A; Division of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA.
  • Krüger Kjaer S; Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA.
  • Høgdall E; School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA.
  • Campbell IG; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Lázaro C; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Pujara MA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
  • Cunningham J; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  • Vierkant R; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Kobenhavn, Denmark.
  • Winham SJ; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Kobenhavn, Denmark.
  • Hildebrandt M; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Kobenhavn, Denmark.
  • Huff C; Department of Pathology, Herlev Hospital, University of Copenhagen, Kobenhavn, Denmark.
  • Li D; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
  • Wu X; Department of Research, Cancer Genomics and Genetics, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Yu Y; Hereditary Cancer Program, Catalan Institute of Oncology, Barcelona, Catalunya, Spain.
  • Permuth JB; Translational Research Laboratory, Catalan Institute of Oncology, Barcelona, Catalunya, Spain.
  • Levine DA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
  • Schildkraut JM; Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
  • Riggan MJ; Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, USA.
  • Berchuck A; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Webb PM; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Group OS; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Cybulski C; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Gronwald J; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Jakubowska A; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA.
  • Lubinski J; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
J Med Genet ; 58(5): 305-313, 2021 05.
Article em En | MEDLINE | ID: mdl-32546565
ABSTRACT

PURPOSE:

The known epithelial ovarian cancer (EOC) susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting that other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.

METHODS:

We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases versus controls were further examined in an independent set of 14 135 EOC cases and 28 655 controls from the Ovarian Cancer Association Consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics.

RESULTS:

The ORs associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 to 5.68; p=0.00068), 1.99 for POLK (95% CI 1.15 to 3.43; p=0.014) and 4.07 for SLX4 (95% CI 1.34 to 12.4; p=0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 to 1.00, p=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive.

CONCLUSIONS:

We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Predisposição Genética para Doença / Proteína do Grupo de Complementação N da Anemia de Fanconi Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Predisposição Genética para Doença / Proteína do Grupo de Complementação N da Anemia de Fanconi Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article