University of Oulu

Nasim Mavaddat, Kyriaki Michailidou, Joe Dennis, Michael Lush, Laura Fachal, Andrew Lee, Jonathan P. Tyrer, Ting-Huei Chen, Qin Wang, Manjeet K. Bolla, Xin Yang, Muriel A. Adank, Thomas Ahearn, Kristiina Aittomäki, Jamie Allen, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Päivi Auvinen, Myrto Barrdahl, Laura E. Beane Freeman, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Leslie Bernstein, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Hiltrud Brauch, Michael Bremer, Hermann Brenner, Adam Brentnall, Ian W. Brock, Angela Brooks-Wilson, Sara Y. Brucker, Thomas Brüning, Barbara Burwinkel, Daniele Campa, Brian D. Carter, Jose E. Castelao, Stephen J. Chanock, Rowan Chlebowski, Hans Christiansen, Christine L. Clarke, J. Margriet Collée, Emilie Cordina-Duverger, Sten Cornelissen, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Isabel dos-Santos-Silva, Martine Dumont, Lorraine Durcan, Miriam Dwek, Diana M. Eccles, Arif B. Ekici, A. Heather Eliassen, Carolina Ellberg, Christoph Engel, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Asta Försti, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Susan M. Gapstur, José A. García-Sáenz, Mia M. Gaudet, Vassilios Georgoulias, Graham G. Giles, Irina R. Gilyazova, Gord Glendon, Mark S. Goldberg, David E. Goldgar, Anna González-Neira, Grethe I. Grenaker Alnæs, Mervi Grip, Jacek Gronwald, Anne Grundy, Pascal Guénel, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Susan E. Hankinson, Elaine F. Harkness, Steven N. Hart, Wei He, Alexander Hein, Jane Heyworth, Peter Hillemanns, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Anthony Howell, Guanmengqian Huang, Keith Humphreys, David J. Hunter, Milena Jakimovska, Anna Jakubowska, Wolfgang Janni, Esther M. John, Nichola Johnson, Michael E. Jones, Arja Jukkola-Vuorinen, Audrey Jung, Rudolf Kaaks, Katarzyna Kaczmarek, Vesa Kataja, Renske Keeman, Michael J. Kerin, Elza Khusnutdinova, Johanna I. Kiiski, Julia A. Knight, Yon-Dschun Ko, Veli-Matti Kosma, Stella Koutros, Vessela N. Kristensen, Ute Krüger, Tabea Kühl, Diether Lambrechts, Loic Le Marchand, Eunjung Lee, Flavio Lejbkowicz, Jenna Lilyquist, Annika Lindblom, Sara Lindström, Jolanta Lissowska, Wing-Yee Lo, Sibylle Loibl, Jirong Long, Jan Lubiński, Michael P. Lux, Robert J. MacInnis, Tom Maishman, Enes Makalic, Ivana Maleva Kostovska, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, John W.M. Martens, Maria Elena Martinez, Dimitrios Mavroudis, Catriona McLean, Alfons Meindl, Usha Menon, Pooja Middha, Nicola Miller, Fernando Moreno, Anna Marie Mulligan, Claire Mulot, Victor M. Muñoz-Garzon, Susan L. Neuhausen, Heli Nevanlinna, Patrick Neven, William G. Newman, Sune F. Nielsen, Børge G. Nordestgaard, Aaron Norman, Kenneth Offit, Janet E. Olson, Håkan Olsson, Nick Orr, V. Shane Pankratz, Tjoung-Won Park-Simon, Jose I.A. Perez, Clara Pérez-Barrios, Paolo Peterlongo, Julian Peto, Mila Pinchev, Dijana Plaseska-Karanfilska, Eric C. Polley, Ross Prentice, Nadege Presneau, Darya Prokofyeva, Kristen Purrington, Katri Pylkäs, Brigitte Rack, Paolo Radice, Rohini Rau-Murthy, Gad Rennert, Hedy S. Rennert, Valerie Rhenius, Mark Robson, Atocha Romero, Kathryn J. Ruddy, Matthias Ruebner, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Daniel F. Schmidt, Rita K. Schmutzler, Andreas Schneeweiss, Minouk J. Schoemaker, Fredrick Schumacher, Peter Schürmann, Lukas Schwentner, Christopher Scott, Rodney J. Scott, Caroline Seynaeve, Mitul Shah, Mark E. Sherman, Martha J. Shrubsole, Xiao-Ou Shu, Susan Slager, Ann Smeets, Christof Sohn, Penny Soucy, Melissa C. Southey, John J. Spinelli, Christa Stegmaier, Jennifer Stone, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Mary Beth Terry, Kathrin Thöne, Rob A.E.M. Tollenaar, Ian Tomlinson, Thérèse Truong, Maria Tzardi, Hans-Ulrich Ulmer, Michael Untch, Celine M. Vachon, Elke M. van Veen, Joseph Vijai, Clarice R. Weinberg, Camilla Wendt, Alice S. Whittemore, Hans Wildiers, Walter Willett, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Drakoulis Yannoukakos, Yan Zhang, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Deborah J. Thompson, Georgia Chenevix-Trench, Jenny Chang-Claude, Marjanka K. Schmidt, Per Hall, Roger L. Milne, Paul D.P. Pharoah, Antonis C. Antoniou, Nilanjan Chatterjee, Peter Kraft, Montserrat García-Closas, Jacques Simard, Douglas F. Easton, Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes, The American Journal of Human Genetics, Volume 104, Issue 1, 2019, Pages 21-34, ISSN 0002-9297, https://doi.org/10.1016/j.ajhg.2018.11.002

Polygenic risk scores for prediction of breast cancer and breast cancer subtypes

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Author: Mavaddat, Nasim1; Michailidou, Kyriaki1,2; Dennis, Joe1;
Lush, Michael1; Fachal, Laura3; Lee, Andrew1; Tyrer, Jonathan P.3; Chen, Ting-Huei4; Wang, Qin1; Bolla, Manjeet K.1; Yang, Xin1; Adank, Muriel A.5; Ahearn, Thomas6; Aittomaki, Kristiina7; Allen, Jamie1; Andrulis, Irene L.8,9; Anton-Culver, Hoda10; Antonenkova, Natalia N.11; Arndt, Volker12; Aronson, Kristan J.13,14; Auer, Paul L.15,16; Auvinen, Paivi17,18,19; Barrdahl, Myrto20; Freeman, Laura E. Beane6; Beckmann, Matthias W.21; Behrens, Sabine20; Benitez, Javier22,23; Bermisheva, Marina24; Bernstein, Leslie25; Blomqvist, Carl26,27; Bogdanova, Natalia, V11,28,29; Bojesen, Stig E.30,31,32; Bonanni, Bernardo33; Borresen-Dale, Anne-Lise34,35; Brauch, Hiltrud36,37,38; Bremer, Michael28; Brenner, Hermann12,38,39,40; Brentnall, Adam41; Brock, Ian W.42; Brooks-Wilson, Angela43,44; Brucker, Sara Y.45; Bruening, Thomas46; Burwinkel, Barbara47,48; Campa, Daniele20,49; Carter, Brian D.50; Castelao, Jose E.51; Chanock, Stephen J.6; Chlebowski, Rowan52; Christiansen, Hans28; Clarke, Christine L.53; Collee, J. Margriet54; Cordina-Duverger, Emilie55; Cornelissen, Sten56; Couch, Fergus J.57; Cox, Angela42; Cross, Simon S.58; Czene, Kamila59; Daly, Mary B.60; Devilee, Peter61,62; Doerk, Thilo29; dos-Santos-Silva, Isabel63; Dumont, Martine64; Durcan, Lorraine65,66; Dwek, Miriam67; Eccles, Diana M.66; Ekici, Arif B.68; Eliassen, A. Heather69,70; Ellberg, Carolina71; Engel, Christoph72,73; Eriksson, Mikael59; Evans, D. Gareth74,75; Fasching, Peter A.21,76; Figueroa, Jonine6,77,78; Fletcher, Olivia79; Flyger, Henrik80; Foersti, Asta81,82; Fritschi, Lin83; Gabrielson, Marike59; Gago-Dominguez, Manuela84,85; Gapstur, Susan M.50; Garcia-Saenz, Jose A.86; Gaudet, Mia M.50; Georgoulias, Vassilios87; Giles, Graham G.88,89,90; Gilyazova, Irina R.24,91; Glendon, Gord8; Goldberg, Mark S.92,93; Goldgar, David E.94,95; Gonzalez-Neira, Anna22; Alnaes, Grethe I. Grenaker34; Grip, Mervi96; Gronwald, Jacek97; Grundy, Anne98; Guenel, Pascal55; Haeberle, Lothar21; Hahnen, Eric99,100; Haiman, Christopher A.101; Hakansson, Niclas102; Hamann, Ute103; Hankinson, Susan E.104; Harkness, Elaine F.105,106,107; Hart, Steven N.108; He, Wei59; Hein, Alexander21; Heyworth, Jane109; Hillemanns, Peter29; Hollestelle, Antoinette110; Hooning, Maartje J.110; Hoover, Robert N.6; Hopper, John L.89; Howell, Anthony111; Huang, Guanmengqian103; Humphreys, Keith59; Hunter, David J.70,112,113; Jakimovska, Milena114; Jakubowska, Anna97,115; Janni, Wolfgang116; John, Esther M.117; Johnson, Nichola79; Jones, Michael E.118; Jukkola-Vuorinen, Arja119; Jung, Audrey20; Kaaks, Rudolf20; Kaczmarek, Katarzyna97; Kataja, Vesa19,120; Keeman, Renske56; Kerin, Michael J.121; Khusnutdinova, Elza24,91; Kiiski, Johanna, I122; Knight, Julia A.123,124; Ko, Yon-Dschun125; Kosma, Veli-Matti19,126,127; Koutros, Stella6; Kristensen, Vessela N.34,35; Kruger, Ute71; Kuehl, Tabea128; Lambrechts, Diether129,130; Le Marchand, Loic131; Lee, Eunjung101; Lejbkowicz, Flavio132,133; Lilyquist, Jenna108; Lindblom, Annika134,135; Lindstrom, Sara136,137; Lissowska, Jolanta138; Lo, Wing-Yee36,37; Loibl, Sibylle139; Long, Jirong140; Lubinski, Jan97; Lux, Michael P.21; MacInnis, Robert J.88,89; Maishman, Tom65,66; Makalic, Enes89; Kostovska, Ivana Maleva114; Mannermaa, Arto19,126,127; Manoukian, Siranoush141; Margolin, Sara142,143; Martens, John W. M.110; Martinez, Maria Elena85,144; Mavroudis, Dimitrios87; McLean, Catriona145; Meindl, Alfons146; Menon, Usha147; Middha, Pooja20,148; Miller, Nicola121; Moreno, Fernando86; Mulligan, Anna Marie149,150; Mulot, Claire151; Munoz-Garzon, Victor M.152; Neuhausen, Susan L.25; Nevanlinna, Heli122; Neven, Patrick153; Newman, William G.74,75; Nielsen, Sune F.30,31; Nordestgaard, Borge G.30,31,32; Norman, Aaron108; Offit, Kenneth154,155; Olson, Janet E.108; Olsson, Hakan71; Orr, Nick156; Pankratz, V. Shane157; Park-Simon, Tjoung-Won29; Perez, Jose I. A.158; Perez-Barrios, Clara159; Peterlongo, Paolo160; Peto, Julian63; Pinchev, Mila132,133; Plaseska-Karanfilska, Dijana114; Polley, Eric C.108; Prentice, Ross15; Presneau, Nadege67; Prokofyeva, Darya91; Purrington, Kristen161; Pylkas, Katri162,163; Rack, Brigitte116; Radice, Paolo164; Rau-Murthy, Rohini155; Rennert, Gad132,133; Rennert, Hedy S.132,133; Rhenius, Valerie3; Robson, Mark155; Romero, Atocha159; Ruddy, Kathryn J.165; Ruebner, Matthias21; Saloustros, Emmanouil166; Sandler, Dale P.167; Sawyer, Elinor J.168; Schmidt, Daniel F.89,169; Schmutzler, Rita K.99,100; Schneeweiss, Andreas170,171; Schoemaker, Minouk J.118; Schumacher, Fredrick172; Schuermann, Peter29; Schwentner, Lukas116; Scott, Christopher108; Scott, Rodney J.173,174,175; Seynaeve, Caroline110; Shah, Mitul3; Sherman, Mark E.176; Shrubsole, Martha J.140; Shu, Xiao-Ou140; Slager, Susan108; Smeets, Ann153; Sohn, Christof170,171; Soucy, Penny64; Southey, Melissa C.177,178; Spinelli, John J.179,180; Stegmaier, Christa181; Stone, Jennifer89,182,183; Swerdlow, Anthony J.118,184; Tamimi, Rulla M.69,70,112; Tapper, William J.185; Taylor, Jack A.167,186; Terry, Mary Beth187; Thoene, Kathrin128; Tollenaar, Rob A. E. M.188; Tomlinson, Ian189,190,191; Truong, Therese55; Tzardi, Maria192; Ulmer, Hans-Ulrich193; Untch, Michael194; Vachon, Celine M.108; van Veen, Elke M.74,75; Vijai, Joseph154,155; Weinberg, Clarice R.195; Wendt, Camilla142,143; Whittemore, Alice S.196,197; Wildiers, Hans153; Willett, Walter70,198,199,200; Winqvist, Robert162,163; Wolk, Alicja102,201; Yang, Xiaohong R.6; Yannoukakos, Drakoulis202; Zhang, Yan12; Zheng, Wei140; Ziogas, Argyrios10; Clarke, Christine53; Balleine, Rosemary; Baxter, Robert; Braye, Stephen; Carpenter, Jane; Dahlstrom, Jane; Forbes, John; Lee, C. Soon; Marsh, Deborah; Morey, Adrienne; Pathmanathan, Nirmala; Scott, Rodney173,174,175; Simpson, Peter; Spigelman, Allan; Wilcken, Nicholas; Yip, Desmond; Zeps, Nikolajs; Sexton, Adrienne; Dobrovic, Alex; Christian, Alice; Trainer, Alison; Fellows, Andrew; Shelling, Andrew; De Fazio, Anna; Blackburn, Anneke; Crook, Ashley; Meiser, Bettina; Patterson, Briony; Clarke, Christobel; Saunders, Christobel; Hunt, Clare; Scott, Clare; Amor, David; Ortega, David Gallego; Marsh, Deb; Edkins, Edward; Salisbury, Elizabeth; Haan, Eric; Macrea, Finlay; Farshid, Gelareh; Lindeman, Geoff; Trench, Georgia203; Mann, Graham; Giles, Graham88,89,90; Gill, Grantley; Thorne, Heather; Campbell, Ian; Hickie, Ian; Caldon, Liz; Winship, Ingrid; Cui, James; Flanagan, James; Kollias, James; Visvader, Jane; Taylor, Jessica; Burke, Jo; Saunus, Jodi; Forbs, John; Hopper, John89; Beesley, Jonathan; Kirk, Judy; French, Juliet; Tucker, Kathy; Wu, Kathy; Phillips, Kelly; Forrest, Laura; Lipton, Lara; Andrews, Leslie; Lobb, Lizz; Walker, Logan; Kentwell, Maira; Spurdle, Mandy; Cummings, Margaret; Gleeson, Margaret; Harris, Marion; Jenkins, Mark; Young, Mary Anne; Delatycki, Martin; Wallis, Mathew; Burgess, Matthew; Brown, Melissa; Southey, Melissa177,178; Bogwitz, Michael; Field, Michael; Friedlander, Michael; Gattas, Michael; Saleh, Mona; Aghmesheh, Morteza; Hayward, Nick; Pachter, Nick; Cohen, Paul; Duijf, Pascal; James, Paul; Simpson, Pete; Fong, Peter; Butow, Phyllis; Williams, Rachael; Kefford, Rick; Simard, Jacques64; Balleine, Rose-Mary; Dawson, Sarah-Jane; Lok, Sheau; O'connell, Shona; Greening, Sian; Nightingale, Sophie; Edwards, Stacey; Fox, Stephen; McLachlan, Sue-Anne; Lakhani, Sunil; Dudding, Tracy; Antill, Yoland; Sahlberg, Kristine K.; Ottestad, Lars; Karesen, Rolf; Schlichting, Ellen; Holmen, Marit Muri; Sauer, Toril; Haakensen, Vilde; Engebraten, Olav; Naume, Bjorn; Fossa, Alexander; Kiserud, Cecile E.; Reinertsen, Kristin, V; Helland, Aslaug; Riis, Margit; Geisler, Juergen; Dunning, Alison M.3; Thompson, Deborah J.1; Chenevix-Trench, Georgia203; Chang-Claude, Jenny20,128; Schmidt, Marjanka K.56,204; Hall, Per59,143; Milne, Roger L.88,89,177; Pharoah, Paul D. P.1,3; Antoniou, Antonis C.1; Chatterjee, Nilanjan6,205,206; Kraft, Peter112; Garcia-Closas, Montserrat6; Easton, Douglas F.1,3
Organizations: 1Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
2Cyprus Inst Neurol & Genet, Dept Electron Microscopy Mol Pathol, CY-1683 Nicosia, Cyprus.
3Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England.
4Laval Univ, Dept Math & Stat, Quebec City, PQ G1V 0A6, Canada.
5Antoni van Leeuwenhoek hosp, Netherlands Canc Inst, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands.
6NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20850 USA.
7Univ Helsinki, Helsinki Univ Hosp, Dept Clin Genet, FIN-00290 Helsinki, Finland.
8Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
9Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
10Univ Calif Irvine, Dept Epidemiol, Genet Epidemiol Res Inst, Irvine, CA 92617 USA.
11NN Alexandrov Res Inst Oncol & Med Radiol, Minsk 223040, BELARUS.
12German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
13Queens Univ, Dept Publ Hlth Sci, Kingston, ON K7L 3N6, Canada.
14Queens Univ, Canc Res Inst, Kingston, ON K7L 3N6, Canada.
15Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA.
16Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.
17Kuopio Univ Hosp, Canc Ctr, SF-70210 Kuopio, Finland.
18Univ Eastern Finland, Inst Clin Med, Oncol, Kuopio 70210, Finland.
19Univ Eastern Finland, Translat Canc Res Area, Kuopio 70210, Finland.
20German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
21Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
22Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Madrid 28029, Spain.
23Biomed Network Rare Dis CIBERER, Madrid 28029, Spain.
24Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450054, Russia.
25Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA 91010 USA.
26Univ Helsinki, Helsinki Univ Hosp, Dept Oncol, FIN-00290 Helsinki, Finland.
27Orebro Univ Hosp, Dept Oncol, S-70185 Orebro, Sweden.
28Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany.
29Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany.
30Copenhagen Univ Hosp, Copenhagen Gen Populat Study Herlev & Gentofte Ho, DK-2730 Herlev, Denmark.
31Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
32Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
33European Inst Oncol IRCCS, IEO, Div Canc Prevent & Genet, I-20141 Milan, Italy.
34Oslo Univ Hosp Radiumhosp, Inst Canc Res, Dept Canc Genet, N-0379 Oslo, Norway.
35Univ Oslo, Fac Med, Inst Clin Med, N-0450 Oslo, Norway.
36Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
37Univ Tubingen, D-72074 Tubingen, Germany.
38German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
39German Canc Res Ctr, Div Prevent Oncol, D-69120 Heidelberg, Germany.
40Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany.
41Queen Mary Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, London EC1M 6BQ, England.
42Univ Sheffield, Sheffield Inst Nucle Acids SInFoNiA, Dept Oncol & Metab, Sheffield S10 2TN, S Yorkshire, England.
43BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
44Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
45Univ Tubingen, Dept Gynecol & Obstet, D-72076 Tubingen, Germany.
46Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med German Social Accid In, D-44789 Bochum, Germany.
47Heidelberg Univ, Dept Obstet & Gynecol, D-69120 Heidelberg, Germany.
48German Canc Res Ctr, C080, Mol Epidemiol Grp, D-69120 Heidelberg, Germany.
49Univ Pisa, Dept Biol, I-56126 Pisa, Italy.
50Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
51IISGS, Oncol & Genet Unit, Xerencia Xest Integrada Vigo SERGAS, Vigo 36312, Spain.
52Univ Calif Los Angeles, Div Med Oncol & Hematol, Los Angeles, CA 90024 USA.
53Univ Sydney, Westmead Inst Med Res, Sydney, NSW 2145, Australia.
54Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3015 CN Rotterdam, Netherlands.
55Univ Paris Saclay, Univ Paris Sud, INSERM, Canc & Environm Grp,Ctr Res Epidemiol & Populat H, F-94805 Villejuif, France.
56Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Div Mol Pathol, NL-1066 CX Amsterdam, Netherlands.
57Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
58Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield S10 2TN, S Yorkshire, England.
59Karolinska Inst, Dept Med Epidemiol & Biostat, S-17165 Stockholm, Sweden.
60Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
61Leiden Univ, Dept Pathol, Med Ctr, NL-2333 ZA Leiden, Netherlands.
62Leiden Univ, Dept Human Genet, Med Ctr, NL-2333 ZA Leiden, Netherlands.
63London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England.
64Univ Laval, Univ Laval Res Ctr, Ctr Hosp Univ Quebec, Genom Ctr, Quebec City, PQ G1V 4G2, Canada.
65Univ Southampton, Fac Med, Southampton Clin Trials Unit, Southampton SO17 6YD, Hants, England.
66Univ Southampton, Canc Sci Acad Unit, Fac Med, Southampton SO17 6YD, Hants, England.
67Univ Westminster, Sch Life Sci, London W1B 2HW, England.
68Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Inst Human Genet, D-91054 Erlangen, Germany.
69Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
70Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
71Lund Univ, Dept Canc Epidemiol, Clin Sci, S-22242 Lund, Sweden.
72Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany.
73Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, D-04103 Leipzig, Germany.
74Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Div Evolut & Genom Sci,Sch Biol Sci, Manchester M13 9WL, Lancs, England.
75Manchester Univ NHS Fdn Trust, St Marys Hosp, Manchester Acad Hlth Sci Ctr, North West Genom Lab Hub,Manchester Ctr Genom Med, Manchester M13 9WL, Lancs, England.
76Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Div Hematol & Oncol, Los Angeles, CA 90095 USA.
77Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Med Sch, Edinburgh EH16 4TJ, Midlothian, Scotland.
78Canc Res UK Edinburgh Ctr, Edinburgh EH4 2XR, Midlothian, Scotland.
79Breast Canc Now Toby Robins Res Ctr, Inst Canc Res, London SW7 3RP, England.
80Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark.
81German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany.
82Lund Univ, Ctr Primary Hlth Care Res, Clin Res Ctr, S-20502 Malmo, Sweden.
83Curtin Univ, Sch Publ Hlth, Perth, WA 6102, Australia.
84Complejo Hosp Univ Santiago, SERGAS, Inst Invest Sanitaria Santiago de Compostela IDIS, Genom Med Grp,Galician Fdn Genom Med, Santiago De Compostela 15706, Spain.
85Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
86Ctr Invest Biomed Red Canc CIBERONC, IdISSC, Hosp Clin San Carlos, Med Oncol Dept, Madrid 28040, Spain.
87Univ Hosp Heraklion, Dept Med Oncol, Iraklion 71110, Greece.
88Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia.
89Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
90Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
91Bashkir State Univ, Dept Genet & Fundamental Med, Ufa 450076, Russia.
92McGill Univ, Dept Med, Montreal, PQ H4A 3J1, Canada.
93McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H4A 3J1, Canada.
94Univ Utah, Dept Dermatol, Sch Med, Salt Lake City, UT 84112 USA.
95Univ Utah, Huntsman Canc Inst, Sch Med, Salt Lake City, UT 84112 USA.
96Univ Oulu, Oulu Univ Hosp, Dept Surg, SF-90220 Oulu, Finland.
97Pomeranian Med Univ, Dept Genet & Pathol, PL-71252 Szczecin, Poland.
98Univ Montreal, CHUM, Ctr Rech, Montreal, PQ H2X 0A9, Canada.
99Univ Hosp Cologne, Ctr Hereditary Breast & Ovarian Canc, D-50937 Cologne, Germany.
100Univ Cologne, Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany.
101Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
102Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden.
103German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany.
104Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
105Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Div Informat Imaging & Data Sci, Manchester M13 9PT, Lancs, England.
106Manchester Univ NHS Fdn Trust, Wythenshawe Hosp, Nightingale Breast Screening Ctr, Manchester M23 9LT, Lancs, England.
107Manchester Univ NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, NIHR Manchester Biomed Res Ctr, Manchester M13 9WL, Lancs, England.
108Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
109Univ Western Australia, Sch Populat & Global Hlth, Perth, WA 6009, Australia.
110Erasmus MC Canc Inst, Dept Med Oncol, Family Canc Clin, NL-3015 CN Rotterdam, Netherlands.
111Univ Manchester, Div Canc Sci, Manchester M13 9PL, Lancs, England.
112Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
113Univ Oxford, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
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Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019071022990
Language: English
Published: Elsevier, 2019
Publish Date: 2019-07-10
Description:

Abstract

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

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Series: American journal of human genetics
ISSN: 0002-9297
ISSN-E: 1537-6605
ISSN-L: 0002-9297
Volume: 104
Issue: 1
Pages: 21 - 34
DOI: 10.1016/j.ajhg.2018.11.002
OADOI: https://oadoi.org/10.1016/j.ajhg.2018.11.002
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: BCAC was funded by Cancer Research UK (C1287/A16563) and by the European Community’s Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the OncoArray was principally funded by Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344), the Ministère de l’Économie, de la Science et de l’Innovation du Québec through Genome Québec, the Quebec Breast Cancer Foundation; NIH grants U19 CA148065 and X01HG007492; and Cancer Research UK (C1287/A10118 and C1287/A16563). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant # PSR-SIIRI-701). Combining the GWAS data was supported in part by the National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148065 (DRIVE, part of the GAME-ON initiative).
Copyright information: © 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/