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Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors.
Lee, Andrew; Yang, Xin; Tyrer, Jonathan; Gentry-Maharaj, Aleksandra; Ryan, Andy; Mavaddat, Nasim; Cunningham, Alex P; Carver, Tim; Archer, Stephanie; Leslie, Goska; Kalsi, Jatinder; Gaba, Faiza; Manchanda, Ranjit; Gayther, Simon; Ramus, Susan J; Walter, Fiona M; Tischkowitz, Marc; Jacobs, Ian; Menon, Usha; Easton, Douglas F; Pharoah, Paul; Antoniou, Antonis C.
  • Lee A; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Yang X; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Tyrer J; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Gentry-Maharaj A; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
  • Ryan A; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK.
  • Mavaddat N; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Cunningham AP; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Carver T; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Archer S; The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Leslie G; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Kalsi J; Department of Women's Cancer, University College London Institute for Women's Health, London, UK.
  • Gaba F; Department of Epidemiology and Public Health, University College London Research, London, UK.
  • Manchanda R; CRUK Barts Cancer Centre, Wolfson Institute of Preventive Medicine, London, UK.
  • Gayther S; CRUK Barts Cancer Centre, Wolfson Institute of Preventive Medicine, London, UK.
  • Ramus SJ; Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK.
  • Walter FM; Department of Health Services Research, London School of Hygiene & Tropical Medicine, London, UK.
  • Tischkowitz M; Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute, Los Angeles, California, USA.
  • Jacobs I; University of New South Wales, School of Women's and Children's Health, Randwick, New South Wales, Australia.
  • Menon U; Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
  • Easton DF; The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Pharoah P; Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
  • Antoniou AC; Department of Women's Cancer, University College London Institute for Women's Health, London, UK.
J Med Genet ; 59(7): 632-643, 2022 07.
Article en En | MEDLINE | ID: mdl-34844974
ABSTRACT

BACKGROUND:

Epithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention.

METHODS:

We developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively.

RESULTS:

Based on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%-10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk.

CONCLUSION:

This multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias de la Mama Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Female / Humans Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Neoplasias de la Mama Tipo de estudio: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Límite: Female / Humans Idioma: En Año: 2022 Tipo del documento: Article