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Polygenic risk modeling for prediction of epithelial ovarian cancer risk

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机构: [1]Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England [2]Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England [3]Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA [4]Radboud Univ Nijmegen Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands [5]Netherlands Comprehens Canc Org, Utrecht, Netherlands [6]Antoni van Leeuwenhoek Hosp, Family Canc Clin, Netherlands Canc Inst, Amsterdam, Netherlands [7]IRCCS, Immunol & Mol Oncol Unit, Veneto Inst Oncol IOV, Padua, Italy [8]Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada [9]Univ Toronto, Dept Mol Genet, Toronto, ON, Canada [10]Univ Calif Irvine, Genet pidemiol Res Inst, Dept Epidemiol, Irvine, CA USA [11]NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, BELARUS [12]Agii Anargiri Canc Hosp, Athens, Greece [13]Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA [14]Lund Univ, Dept Canc Epidemiol, Clin Sci, Lund, Sweden [15]Vall Hebron Inst Oncol, Hereditary Canc Genet Grp, Barcelona, Spain [16]Univ Hosp Vall Hebron, Dept Med Oncol, Barcelona, Spain [17]Rutgers Canc Inst New Jersey, Canc Prevent & Control Program, New Brunswick, NJ USA [18]Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland [19]Univ Iceland, Fac Med, BMC Biomed Ctr, Reykjavik, Iceland [20]Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr ER EMN, Dept Gynecol & Obstet, Erlangen, Germany [21]Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Dept Med,Sch Med, Nashville, TN USA [22]Biomed Network Rare Dis CIBERER, Madrid, Spain [23]Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Madrid, Spain [24]Russian Acad Sci, Inst Biochem & Genet, Ufa Fed Res Ctr, Ufa, Russia [25]Univ Hlth Network, Princess Margaret Hosp, Div Gynecol Oncol, Toronto, ON, Canada [26]Haukeland Hosp, Dept Obstet & Gynecol, Bergen, Norway [27]Univ Bergen, Ctr Canc Biomarkers CCBIO, Dept Clin Sci, Bergen, Norway [28]NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA [29]Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany [30]Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany [31]European Inst Oncol IRCCS, Div Canc Prevent & Genet, IEO, Milan, Italy [32]Lund Univ, Dept Oncol, Lund, Sweden [33]Skane Univ Hosp, Dept Oncol, Lund, Sweden [34]Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England [35]Maria Sklodowska Curie Natl Res Inst Oncol, Dept Pathol & Lab Diagnost, Warsaw, Poland [36]Univ Helsinki, Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland [37]Huntsman Canc Inst, Dept Med, Salt Lake City, UT USA [38]Univ Hosp, SOD Genet Mol, Pisa, Italy [39]Peter MacCallum Canc Ctr, Melbourne, Vic, Australia [40]Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia [41]Roswell Park Canc Inst, Canc Pathol & Prevent, Div Canc Prevent & Populat Sci, Buffalo, NY USA [42]Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA [43]German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany [44]Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg UCCH, Canc Epidemiol Grp, Hamburg, Germany [45]NCI, NIH, US Dept HHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA [46]Tianjin Med Univ Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China [47]Univ Sydney, Ctr Canc Res, Westmead Inst Med Res, Sydney, NSW, Australia [48]Westmead Hosp, Dept Gynaecol Oncol, Sydney, NSW, Australia [49]Columbia Univ, Dept Pediat, New York, NY USA [50]Columbia Univ, Dept Med, New York, NY USA [51]Univ Ghent, Ctr Med Genet, Ghent, Belgium [52]Dept Tumour Biol, INSERM U830, Paris, France [53]Inst Curie, Paris, France [54]Mines ParisTech, Fontainebleau, France [55]Univ Cologne, Fac Med, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [56]Univ Cologne, Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [57]Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM USA [58]Alberta Hlth Serv, Dept Canc Epidemiol & Prevent Res, Calgary, AB, Canada [59]Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA [60]Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA [61]Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, 1275 York Ave, New York, NY 10021 USA [62]Hosp Clin San Carlos, IdISSC Inst Invest Sanitaria, Mol Oncol Lab, CIBERONC, Madrid, Spain [63]NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA [64]Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA [65]Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands [66]Leiden Univ, Dept Human Genet, Med Ctr, Leiden, Netherlands [67]Vall dHebron Inst Oncol VHIO, Oncogenet Grp, Barcelona, Spain [68]Univ Hosp Vall dHebron, Clin & Mol Genet Area, Barcelona, Spain [69]City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA [70]Univ Utah, Huntsman Canc Inst, Dept Populat Hlth Sci, Salt Lake City, UT USA [71]Univ Penn, Basser Ctr BRCA, Abramson Canc Ctr, Philadelphia, PA USA [72]EV Kliniken Essen Mitte KEM, Dept Gynecol & Gynecol Oncol, Essen, Germany [73]Dr HorstSchmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, Wiesbaden, Germany [74]Friedrich Schiller Univ, Dept Gynaecol, Jena Univ Hosp, Jena, Germany [75]Univ Southampton, Fac Med, Southampton, Hants, England [76]Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA [77]Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [78]Harvard Med Sch, Channing Div Network Med, Boston, MA 02115 USA [79]Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany [80]Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, Leipzig, Germany [81]Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Biol Sci,Div Evolut & Genom Sci, Manchester, Lancs, England [82]Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester Ctr Genom Med, North West Genom Lab Hub,St Marys Hosp, Manchester, Lancs, England [83]Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA [84]Imperial Coll London, Div Canc, Dept Surg & Canc, London, England [85]Imperial Coll London, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England [86]Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic [87]Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, Ramat Gan, Israel [88]Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel [89]Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA [90]Univ Calif Los Angeles, Sch Publ Hlth, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA [91]Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA [92]Univ Florence, Dept Expt & Clin Biomed Sci Mario Serio, Med Genet Unit, Florence, Italy [93]Canc Council Victoria, Canc Epidemiol Div, Melbourne, Vic, Australia [94]Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia [95]Monash Univ, Sch Clin Sci, Precis Med, Monash Hlth, Clayton, Vic, Australia [96]Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA [97]Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Genet Program, Los Angeles, CA 90048 USA [98]NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA [99]Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland [100]QIMR Berghofer Med Res Inst, Populat Hlth Dept, Brisbane, Qld, Australia [101]Univ Cologne, Fac Med, Ctr Integrated Oncol CIO, Cologne, Germany [102]Univ Cologne, Univ Hosp Cologne, Ctr Integrated Oncol CIO, Cologne, Germany [103]Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA [104]Karolinska Inst, Inst Environm Med, Stockholm, Sweden [105]German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany [106]Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark [107]Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA [108]Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA [109]Natl Univ Singapore, Singapore, Singapore [110]Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore [111]Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore [112]Humboldt Univ, Berlin, Germany [113]Berlin Inst Hlth, Dept Gynecol, Ctr Oncol Surg,Freie Univ Berlin, Charite Campus Virchow Klinikum,Charite Univ Med, Berlin, Germany [114]Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA [115]Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark [116]Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark [117]Univ Copenhagen, Rigshosp, Dept Gynaecol, Copenhagen, Denmark [118]Roswell Park Canc Inst, Ctr Immunotherapy, Buffalo, NY 14263 USA [119]Vancouver Gen Hosp, BC Canc, Vancouver, BC, Canada [120]Univ British Columbia, British Columbias Ovarian Canc Res OVCARE Program, Vancouver, BC, Canada [121]Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada [122]Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada [123]BC Canc Res Ctr, Dept Mol Oncol, Vancouver, BC, Canada [124]NN Petrov Inst Oncol, St Petersburg, Russia [125]Hereditary Breast & Ovarian Canc Res Grp Netherla, Coordinating Ctr, Netherlands Canc Inst, Amsterdam, Netherlands [126]Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA [127]Pomeranian Med Univ, Independent Lab Mol Biol & Genet Diagnost, Szczecin, Poland [128]Peter MacCallum Canc Ctr, Parkville Familial Canc Ctr, Melbourne, Vic, Australia [129]Vilnius Univ Hosp, Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania [130]State Res Inst Ctr Innovat Med, Vilnius, Lithuania [131]Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland [132]Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA [133]Stanford Univ, Stanford Canc Inst, Dept Med, Div Oncol,Sch Med, Stanford, CA 94305 USA [134]Inst Canc Res, Div Genet & Epidemiol, London, England [135]Seoul Natl Univ, Dept Prevent Med, Coll Med, Seoul, South Korea [136]Seoul Natl Univ, Dept Biomed Sci, Grad Sch, Seoul, South Korea [137]Seoul Natl Univ, Canc Res Inst, Seoul, South Korea [138]Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA [139]UC Davis Med Ctr, Dept Pathol & Lab Med, Sacramento, CA USA [140]Med Univ South Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA [141]St Petersburg State Univ, St Petersburg, Russia [142]Sungkyunkwan Univ, Samsung Med Ctr, Dept Obstet & Gynecol, Sch Med, Seoul, South Korea [143]City Hope Natl Med Ctr, Clin Canc Genet Community Res Network, Duarte, CA USA [144]Hong Kong Hereditary Breast Canc Family Registry, Canc Genet Ctr, Happy Valley, Hong Kong, Peoples R China [145]Univ Hong Kong, Dept Surg, Pok Fu Lam, Hong Kong, Peoples R China [146]Hong Kong Sanat & Hosp, Dept Surg, Happy Valley, Hong Kong, Peoples R China [147]VIB Ctr Canc Biol, Leuven, Belgium [148]Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium [149]Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA [150]Catalan Inst Oncol, Hereditary Canc Program, CIBERONC, ONCOBELL IDIBELL IGTP, Barcelona, Spain [151]BC Canc, Canc Control Res, Vancouver, BC, Canada [152]Genet Epidemiol Canc Team, Inserm U900, Paris, France [153]NYU Langone Med Ctr, Laura & Isaac Pearlmutter Canc Ctr, Gynecol Oncol, New York, NY USA [154]Genome Inst Singapore, Human Genet Div, Singapore, Singapore [155]Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA [156]Univ Texas MD Anderson Canc Ctr, Clin Canc Genet Program, Houston, TX 77030 USA [157]Univ Pittsburgh, Magee Womens Hosp, Sch Med, Pittsburgh, PA 15213 USA [158]Fdn IRCCS Ist Nazl Tumori Milano, Dept Med Oncol & Hematol, Unit Med Genet, Milan, Italy [159]Duke Univ Hosp, Dept Surg, Durham, NC USA [160]Univ Hawaii, Canc Ctr, Canc Epidemiol Program, Honolulu, HI 96822 USA [161]Aichi Canc Ctr Res Inst, Div CancerEpidemiol & Prevent, Nagoya, Aichi, Japan [162]Nagoya Univ, Div Canc Epidemiol, Grad Sch Med, Nagoya, Aichi, Japan [163]Samuel Lunenfeld Res Inst, Publ Hlth Ontario, Toronto, ON, Canada [164]Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England [165]Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland [166]UCL, Inst Clin Trials & Methodol, MRC Clin Trials Unit UCL, London, England [167]Roswell Park Canc Inst, NRG Oncol Stat & Data Management Ctr, Buffalo, NY USA [168]Roswell Park Canc Inst, Div Canc Prevent & Control, Buffalo, NY 14263 USA [169]Womens Canc Res Ctr, Magee Womens Res Inst, Pittsburgh, PA USA [170]Hillman Canc Ctr, Womens Canc Res Ctr, Pittsburgh, PA USA [171]Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA [172]Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA [173]Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA [174]Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland [175]Natl Canc Ctr, Canc Genet Serv, Singapore, Singapore [176]Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore [177]Odense Univ Hosp, Dept Clin Genet, Odence C, Denmark [178]Latvian Biomed Res & Study Ctr, Riga, Latvia [179]Roswell Park Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA [180]Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, Dept Canc Biol & Genet, 1275 York Ave, New York, NY 10021 USA [181]Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA [182]Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary [183]Univ Hosp Leuven, Dept Obstet & Gynaecol, Div Gynecol Oncol, Leuven, Belgium [184]Leuven Canc Inst, Leuven, Belgium [185]Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA [186]Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA [187]Ctr Invest Red Enfermedades Raras CIBERER, Madrid, Spain [188]QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia [189]Aalborg Univ Hosp, Mol Diagnost, Aalborg, Denmark [190]Aalborg Univ Hosp, Clin Canc Res Ctr, Aalborg, Denmark [191]Aalborg Univ, Dept Clin Med, Aalborg, Denmark [192]Portuguese Oncol Inst, Dept Genet, Porto, Portugal [193]H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA [194]IFOM FIRC Inst Mol Oncol, Genome Diagnost Program, Milan, Italy [195]Bashkir State Univ, Dept Genet & Fundamental Med, Ufa, Russia [196]Fdn IRCCS Ist Nazl Tumori INT, Dept Res, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy [197]Karolinska Inst, Clin Genet, Stockholm, Sweden [198]Duke Univ Hosp, Dept Gynecol Oncol, Durham, NC USA [199]Yale Sch Publ Hlth, Chron Dis Epidemiol, New Haven, CT USA [200]Fox Chase Canc Ctr, Populat Studies Facil, 7701 Burholme Ave, Philadelphia, PA 19111 USA [201]NIEHS, NIH, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA [202]Fdn Publ Galega Med Xenom, Santiago De Compostela, Spain [203]Inst Invest Sanitaria Santiago de Compostela, Santiago De Compostela, Spain [204]Univ Laval, Res Ctr, Genom Ctr, Ctr Hosp Univ Quebec, Quebec City, PQ, Canada [205]Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany [206]Univ Cologne, Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany [207]Hebei Med Univ, Hosp 4, Dept Obstet & Gynaecol, Shijiazhuang, Hebei, Peoples R China [208]Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA [209]Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA [210]Med Univ Vienna, Dept OB GYN, Vienna, Austria [211]Med Univ Vienna, Comprehens Canc Ctr, Vienna, Austria [212]Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England [213]Univ Melbourne, Dept Clin Pathol, Melbourne, Vic, Australia [214]Royal Alexandra Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Edmonton, AB, Canada [215]Inst Curie, Serv Genet, Paris, France [216]Univ Paris 05, Paris, France [217]Univ S Florida, Coll Med, Epidemiol Ctr, Tampa, FL USA [218]Inst Canc Res, Div Breast Canc Res, London, England [219]Univ Porto, Biomed Sci Inst ICBAS, Porto, Portugal [220]Canc Res Malaysia, Breast Canc Res Programme, Subang Jaya, Selangor, Malaysia [221]Univ Malaya, Fac Med, Dept Surg, Kuala Lumpur, Malaysia [222]Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA [223]Harvard Med Sch, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA [224]Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA [225]Univ Pittsburgh, Magee Womens Hosp, Dept Med, Sch Med, Pittsburgh, PA USA [226]McGill Univ, Dept Human Genet, Montreal, PQ, Canada [227]McGill Univ, Dept Oncol, Montreal, PQ, Canada [228]Univ Cambridge, Dept Med Genet, Cambridge, England [229]Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA [230]Ohio State Univ, Dept Canc Biol & Genet, Columbus, OH 43210 USA [231]Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia [232]Univ Oxford, Canc Epidemiol Unit, Oxford, England [233]Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA [234]Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands [235]Univ Pretoria, Dept Genet, Arcadia, South Africa [236]Complejo Hosp Univ Santiago, Inst Invest Sanitaria Santiago de Compostela, SERGAS, Santiago De Compostela, Spain [237]Vanderbilt Univ, Dept Obstet & Gynecol, Dept Biomed Sci, Div Quantitat Sci,Med Ctr, Nashville, TN USA [238]Duke Canc Inst, Canc Control & Populat Sci, Durham, NC USA [239]Duke Univ Hosp, Dept Community & Family Med, Durham, NC USA [240]NIEHS, NIH, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA [241]City Hope Natl Med Ctr, Clin Canc Genom, Duarte, CA USA [242]Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA [243]Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA [244]Uppsala Univ, Dept Surg Sci, Uppsala, Sweden [245]Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia [246]Hebei Med Univ, Hosp 4, Dept Mol Biol, Shijiazhuang, Hebei, Peoples R China [247]Natl Ctr Sci Res Demokritos, Mol Diagnost Lab, INRASTES, Athens, Greece [248]Charles Univ Prague, Fac Med 1, Inst Biochem & Expt Oncol, Prague, Czech Republic [249]Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Dept Obstet & Gynecol, Losangeles, CA USA [250]Royal Pass Rd, Tampa, FL USA [251]Univ NSW Sydney, Fac Med, Sch Womens & Childrens Hlth, Sydney, NSW, Australia [252]Univ NSW Sydney, Lowy Canc Res Ctr, Adult Canc Program, Sydney, NSW, Australia [253]Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA [254]Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA [255]Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA [256]Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA
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摘要:
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

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大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 遗传学
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大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 遗传学
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Q1 GENETICS & HEREDITY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
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Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 GENETICS & HEREDITY

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第一作者机构: [1]Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England
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