Identification of six new susceptibility loci for invasive epithelial ovarian cancer

descriptionPublicationkeyboard_double_arrow_right Article 12 Jan 2015 United Kingdom, Poland, Netherlands, Netherlands, Denmark, Netherlands, United Kingdom, United Kingdom, Netherlands, Netherlands, United Kingdom, Italy, United Kingdom, South Africa, Netherlands, Spain, United States, Netherlands, United States, Denmark, Italy, Italy, Iceland, Australia English Publisher:Springer Science and Business Media LLCJournal:Nature Genetics, volume 47, pages 164-171 (issn: 1061-4036, eissn: 1546-1718,

Copyright policy )Funded by:WT | The genetics of weight, B..., NIH | Follow-up of Ovarian Canc..., EC | COGS

Authors: Tyrer, Jonathan; Shen, Howard C; Lawrenson, Kate; Lee, Janet M; Spindler, Tassja J; Lin, Yvonne G; Pejovic, Tanja; +193 Authors

Tyrer, Jonathan; Shen, Howard C; Lawrenson, Kate; Lee, Janet M; Spindler, Tassja J; Lin, Yvonne G; Pejovic, Tanja; Bean, Yukie; Li, Qiyuan; Coetzee, Simon; Hazelett, Dennis; Isaccs, Claudine; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A; Wicklund, Kristine G; Rossing, Mary Anne; Rudolph, Anja; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Lele, Shashi; Wilkens, Lynne R; Goodman, Marc T; Thompson, Pamela J; Shvetsov, Yurii B; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Pelttari, Liisa M; Butzow, Ralf; Modugno, Francesmary; Kelley, Joseph L; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Matsuo, Keitaro; Hosono, Satoyo; Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid; Hasmad, Hanis Nazihah; Azmi, Mat Adenan Noor; Woo, Yin-Ling; Fridley, Brooke L; Goode, Ellen L; Vierkant, Robert A; Bruinsma, Fiona; Liang, Dong; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S; Schildkraut, Joellen M; Concannon, Patrick; Weber, Rachel Palmieri; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Orlow, Irene; Olson, Sara H; Krakstad, Camilla; Salvesen, Helga B; Tangen, Ingvild L; Bjorge, Line; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Kellar, Melissa; Brooks-Wilson, Angela; Kelemen, Linda E; Cook, Linda S; Le, Nhu D; Yang, Hannah; Lissowska, Jolanta; Brinton, Louise A; Wentzensen, Nicolas; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Baker, Helen; Song, Honglin; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Rothstein, Joseph H; McGuire, Valerie; Sieh, Weiva; Ji, Bu-Tian; Zheng, Wei; Shu, Xiao-Ou; Gao, Yu-Tang; Rosen, Barry; Risch, Harvey A; McLaughlin, John R; Monteiro, Alvaro N; Chen, Ann; Lin, Hui-Yi; Permuth-Wey, Jenny; Sellers, Thomas A; Tsai, Ya-Yu; Chen, Zhihua; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Lee, Alice W; Wu, Anna H; Pearce, Celeste L; Coetzee, Gerry; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Timorek, Agnieszka; Rzepecka, Iwona K; Kupryjanczyk, Jolanta; Freedman, Matt; Noushmehr, Houtan; Gayther, Simon; Pharoah, Paul P; Parsons, Peter G; Hayward, Nicholas K; Purdie, David M; Whiteman, David C; Bowtell, D; Chenevix-Trench, G; Green, Adele C; Webb, P; deFazio, A; Gertig, D; Goldgar, David E; John, Esther M; Terry, Mary Beth; Whittemore, Alice S; Buys, Saundra S; Chung, Wendy K; Daly, Mary B; Southey, Melissa; Miron, Alex; Janavicius, Ramunas; Rudaitis, Vilius; Eglitis, Janis; Tihomirova, Laima; Nikitina-Zake, Liene; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Steele, Linda; Neuhausen, Susan L; Ding, Yuan Chun; Gerdes, Anne-Marie; Ejlertsen, Bent; Nielsen, Finn C; Jønson, Lars; Andersen, Mette K; Hansen, Thomas V O; Lee, Andrew; Antoniou, Antonis C; Barrowdale, Daniel; Dennis, Joe; Kuchenbaecker, Karoline B; McGuffog, Lesley; Healey, Sue; Easton, Douglas F; Lee, Adam; Wang, Chen; Cunningham, Julie; Hart, Steven; Slager, Susan; Lasa, Adriana; Osorio, Ana; Benitez, Javier; Godino, Javier; Tejada, Maria-Isabel; Garcia, Maria Jose; Duran, Mercedes; Hall, Per; Dicks, Ed; Fontaine, Annette; Komenaka, Ian; Weitzel, Jeffrey N;

doi: 10.1038/ng.3185

pmid: 25581431

pmc: PMC4445140

handle: 2445/127263 , 20.500.12530/23068 , 10261/157705 , https://repository.ubn.ru.nl/handle/2066/153049 , 11370/f35d4105-162a-4682-9739-b4f662253170 , 1887/101430 , 2066/153049 , 10807/148619 , 11573/869548 , 2158/1041467 , 2336/558549 , 11343/269020 , 2263/44069

Identification of six new susceptibility loci for invasive epithelial ovarian cancer

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Abstract

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

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United Kingdom, Poland, Netherlands, Netherlands, Denmark, Netherlands, United Kingdom, United Kingdom, Netherlands, Netherlands, United Kingdom, Italy, United Kingdom, South Africa, Netherlands, Spain, United States, Netherlands, United States, Denmark, Italy, Italy, Iceland, Australia

Related Organizations

University of Manchester
United Kingdom
Vilnius University
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Washington State University
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European Institute of Oncology
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Keywords

Developmental genetics, High-risk, Càncer d'ovari, Carcinoma, Ovarian Epithelial, Brca2 mutation carriers, Breast Cancer Family Registry, Genes, Reporter, Ovarian Epithelial, Aetiology, Cancer, Genetics & Heredity, Ovarian Neoplasms, Human elg1, COMMON VARIANTS, BRCA2 Protein/genetics, Genome-Wide Association Study/methods, EMC MM-03-47-11, Australian Ovarian Cancer Study Group, Disease susceptibility, Invasive, Genotype, Quantitative Trait Loci, Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences, 610, Article, EMBRACE, GEMO Study Collaborators, Ovarian Neoplasms/genetics, 1311 Genetics, SDG 3 - Good Health and Well-being, Ovarian cancer, Australian Cancer Study, Genetics, BREAST-CANCER, Humans, Polymorphism, GENOME-WIDE ASSOCIATION, Reporter, METAANALYSIS, Alleles, Human genome, Prevention, Common variants, ABO BLOOD-GROUP, Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences, epithelial ovarian cancer., Single nucleotide polymorphisms, Radboudumc 17: Women's cancers RIMLS: Radboud Institute for Molecular Life Sciences, Genes, Adolescent; Adult; Alleles; BRCA1 Protein; BRCA2 Protein; Female; Genes, Reporter; Genome-Wide Association Study; Genotype; Heterozygote; Humans; Mutation; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Quantitative Trait Loci; Risk; Young Adult; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Genetics, Eggjastokkar, Myopodin, Mutation, EMC MM-03-86-01, Developmental Biology, Epithelial cells, Genoma humà, Medical and Health Sciences, Neoplasms, BRCA2 MUTATION CARRIERS, 2.1 Biological and endogenous factors, Neoplasms, Glandular and Epithelial, EMC MGC-02-96-01, Breast-cancer, RISK, Cèl·lules epitelials, Genome-wide association, HUMAN ELG1, Nucleotides, BRCA1 Protein, Glandular and Epithelial, GENETIC-VARIATION, Single Nucleotide, Biological Sciences, Metaanalysis, Ovarian Cancer, Radboudumc 14: Tumours of the digestive tract RIMLS: Radboud Institute for Molecular Life Sciences, Consortium of Investigators of Modifiers of BRCA1 and BRCA2, Glandular and Epithelial/genetics, Female, Genètica del desenvolupament, Adult, Risk, MYOPODIN, Heterozygote, Genetic factors, Adolescent, Adolescent; adult; alleles; BRCA1 protein; BRCA2 protein; female; genes, reporter; genome-wide association study; genotype; heterozygote; humans; mutation; neoplasms, glandular and epithelial; ovarian neoplasms; quantitative trait loci; risk; young adult; genetic predisposition to disease; polymorphism, single nucleotide; genetics, Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences, Polymorphism, Single Nucleotide, Young Adult, Rare Diseases, Genetic Predisposition to Disease, HEBON, Krabbamein, BRCA2 Protein, Carcinoma, Human Genome, Arfgengi, Nucleòtids, Abo blood-group, BRCA1 Protein/genetics, KConFab Investigators, Epithelial ovarian cancer (EOC), Genome-Wide Association Study

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