Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci.

Autor:	DeVries AA; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Tyrer JP; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Peng PC; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Coetzee SG; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Reyes AL; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Plummer JT; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Applied Genomics, Computation and Translational Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Davis BD; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Applied Genomics, Computation and Translational Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Chen SS; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.; Applied Genomics, Computation and Translational Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Dezem FS; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Aben KKH; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.; Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands., Anton-Culver H; Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA., Antonenkova NN; N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus., Beckmann MW; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany., Beeghly-Fadiel A; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Berchuck A; Department of Gynecologic Oncology, Duke University Hospital, Durham, NC, USA., Bogdanova NV; N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.; Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Bogdanova-Markov N; Institute of Human Genetics, University of Münster, Münster, Germany., Brenton JD; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Butzow R; Department of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Campbell I; Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia., Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Chenevix-Trench G; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Cook LS; Epidemiology, School of Public Health, University of Colorado, Aurora, CO, USA.; Community Health Sciences, University of Calgary, Calgary, AB, Canada., DeFazio A; Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, New South Wales, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia.; The Daffodil Centre, a joint venture with Cancer Council NSW, The University of Sydney, Sydney, New South Wales, Australia., Doherty JA; Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA., Dörk T; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Eccles DM; Faculty of Medicine, University of Southampton, Southampton, UK., Eliassen AH; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Fasching PA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA., Fortner RT; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Giles GG; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Goode EL; Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA., Goodman MT; Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Gronwald J; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Håkansson N; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden., Hildebrandt MAT; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Huff C; Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Huntsman DG; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Jensen A; Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark., Kar S; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; Section of Translational Epidemiology, Division of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Karlan BY; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA., Khusnutdinova EK; Institute of Biochemistry and Genetics, Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.; Saint Petersburg State University, Saint Petersburg, Russia., Kiemeney LA; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Kjaer SK; Department of Lifestyle, Reproduction and Cancer, Danish Cancer Society Research Center, Copenhagen, Denmark.; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Kupryjanczyk J; Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Labrie M; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Lambrechts D; VIB Center for Cancer Biology, VIB, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium., Le ND; Cancer Control Research, BC Cancer, Vancouver, BC, Canada., Lubiński J; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., May T; Division of Gynecologic Oncology, University Health Network, Princess Margaret Hospital, Toronto, Ontario, Canada., Menon U; MRC Clinical Trials Unit, Institute of Clinical Trials & Methodology, University College London, London, UK., Milne RL; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia., Modugno F; Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA, USA.; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Monteiro AN; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA., Moysich KB; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA., Odunsi K; Department of Oncology, University of Chicago Medicine Comprehensive Cancer Center, Chicago, IL, USA.; Department of Obstetrics and Gynecology, University of Chicago Medicine Comprehensive Cancer Center, Chicago, IL, USA., Olsson H; Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden., Pearce CL; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Pejovic T; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, USA., Ramus SJ; School of Women's and Children's Health, Faculty of Medicine and Health, University of NSW Sydney, Sydney, New South Wales, Australia.; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, Australia., Riboli E; Imperial College London, London, UK., Riggan MJ; Department of Gynecologic Oncology, Duke University Hospital, Durham, NC, USA., Romieu I; Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France., Sandler DP; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA., Schildkraut JM; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Setiawan VW; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Sieh W; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Song H; Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Sutphen R; Epidemiology Center, College of Medicine, University of South Florida, Tampa, FL, USA., Terry KL; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Thompson PJ; Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Titus L; Muskie School of Public Policy, Public Health, Portland, ME, USA., Tworoger SS; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA., Van Nieuwenhuysen E; Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Leuven Cancer Institute, Leuven, Belgium., Edwards DV; Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Department of Biomedical Sciences, Women's Health Research, Vanderbilt University Medical Center, Nashville, TN, USA., Webb PM; Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Wentzensen N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Whittemore AS; Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA., Wolk A; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Wu AH; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Ziogas A; Department of Medicine, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA., Freedman ML; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Lawrenson K; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Women's Cancer Program at the Samuel Oschin Cancer Institute Cedars-Sinai Medical Center, Los Angeles, CA, USA., Pharoah PDP; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Easton DF; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Gayther SA; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Jones MR; Center for Bioinformatics and Functional Genomics, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2022 Nov 14; Vol. 114 (11), pp. 1533-1544.
DOI:	10.1093/jnci/djac160
Abstrakt:	Background: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort. Methods: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types. Results: We identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P < .001) were identified for rare CNVs. Risk-associated CNVs were enriched (P < .05) at known EOC risk loci identified by genome-wide association study. Noncoding CNVs were enriched in active promoters and insulators in EOC-related cell types. Conclusions: CNVs in BRCA1 have been previously reported in smaller studies, but their observed frequency in this large population-based cohort, along with the CNVs observed at BRCA2 and RAD51C gene loci in EOC cases, suggests that these CNVs are potentially pathogenic and may contribute to the spectrum of disease-causing mutations in these genes. CNVs are likely to occur in a wider set of susceptibility regions, with potential implications for clinical genetic testing and disease prevention. (© The Author(s) 2022. Published by Oxford University Press.)
Databáze:	MEDLINE
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