1. Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk
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V. Wendy Setiawan, Ana Osorio, Liv Cecilie Vestrheim Thomsen, Francesca Gensini, Harsha Pathak, Barbara Wappenschmidt, Ingo B. Runnebaum, Javier Benitez, Rita K. Schmutzler, Jeffrey N. Weitzel, Yin Ling Woo, Kenneth Offit, Anthony N. Karnezis, Eitan Friedman, Jacques Simard, James M. Flanagan, Pedro Pérez-Segura, Siranoush Manoukian, Melissa C. Southey, Ramunas Janavicius, Finn Cilius Nielsen, Graham G. Giles, Usha Menon, Ava Kwong, Anna H. Wu, Thomas Hansen, Cristina Rodríguez-Antona, Maria A. Caligo, Argyrios Ziogas, Allison DePersia, Anna P. Sokolenko, Clarice R. Weinberg, Hoda Anton-Culver, Digna R. Velez Edwards, Jennifer B. Permuth, Patricia A. Ganz, Ana Vega, Keitaro Matsuo, Heli Nevanlinna, Frances Wang, Natalia Antonenkova, Claudine Isaacs, Conxi Lázaro, Melissa C. Larson, Henriette Roed Nielsen, Byoung-Gie Kim, Andreas du Bois, Dale P. Sandler, Anna Jakubowska, Paul D.P. Pharoah, Jenny Lester, Paolo Radice, Natalia Bogdanova, Lambertus A. Kiemeney, Mary Anne Rossing, Thilo Dörk, Ruea-Yea Huang, Judy Garber, Taymaa May, Diana Eccles, Mary Beth Terry, Jenny Chang-Claude, Jeffrey R. Marks, Dominique Stoppa-Lyonnet, Heather Eliassen, Douglas A. Levine, Phuong L. Mai, Gerasimos Aravantinos, Hui Cai, Britton Trabert, Amanda Black, Noura Mebirouk, Robin de Putter, Rayna K. Matsuno, Ralf Bützow, Joanne Ngeow Yuen Yie, James D. Brenton, Nadine Tung, Drakoulis Yannoukakos, Jonathan Tyrer, L Yan, Yen Y. Tan, Ian Komenaka, Simona Agata, Honglin Song, Tanja Pejovic, Marjorie J. Riggan, Antonis C. Antoniou, Katja K.H. Aben, Goska Leslie, Eric A. Ross, Estrid Høgdall, Kang Shan, Holly R. Harris, Eleanor Davies, Liene Nikitina-Zake, Florian Heitz, Stephen J. Chanock, Matthew Jones, Beth Y. Karlan, Matthias W. Beckmann, Penelope M. Webb, John L. Hopper, Peter A. Fasching, Jacek Gronwald, kConFab Investigators, Ana Peixoto, Joellen M. Schildkraut, Renée T. Fortner, Susan L. Neuhausen, Daehee Kang, Anthony J. Swerdlow, Lesley McGuffog, Marco Montagna, Paolo Peterlongo, Daniel R. Barnes, Marina Bermisheva, Alicja Wolk, Yuan Chun Ding, Marc Tischkowitz, Gord Glendon, Elza Khusnutdinova, Julie M. Cunningham, Saundra S. Buys, Albina N. Minlikeeva, Jennifer A. Doherty, Annemieke H. van der Hout, Austin Miller, Fergus J. Couch, Fabienne Lesueur, Peter Devilee, Kristin K. Zorn, Daniel Barrowdale, Christian F. Singer, Line Bjørge, Åke Borg, Diether Lambrechts, Shelley S. Tworoger, Allan Jensen, Ute Hamann, Douglas F. Easton, Bernardo Bonanni, Alvaro N.A. Monteiro, Johanna Rantala, Marc T. Goodman, Ellen Valen, Wei Zheng, Thomas A. Sellers, Marcus Q. Bernardini, Alice S. Whittemore, Kunle Odunsi, Inge Søkilde Pedersen, Laura Papi, Mads Thomassen, Allison W. Kurian, Emily White, Penny Soucy, D. Gareth Evans, Lenka Foretova, Kathryn L. Terry, Ruth C. Travis, Claus Høgdall, Hebon Investigators, Darya Prokofyeva, Stacey J. Winham, Yoke-Eng Chiew, Eileen Dareng, Jan Lubinski, Elizabeth Munro, Oskar T. Johannsson, Linda E. Kelemen, Kexin Chen, Xin Yang, Manuel R. Teixeira, Anna M. Piskorz, Edith Olah, Helen Steed, Beth N. Peshkin, Georgia Chenevix-Trench, Andrew K. Godwin, Pamela J. Thompson, Chad D. Huff, Rosa B. Barkardottir, Muriel A. Adank, Mikael Hartman, Linda J. Titus, Weiva Sieh, Simon A. Gayther, Peter J. Hulick, Michael T. Parsons, Elisa V. Bandera, Amanda E. Toland, Miguel de la Hoya, Orland Diez, Alicia Beeghly-Fadiel, Rebecca Sutphen, Francesmary Modugno, Judith Balmaña, Christoph Engel, Harvey A. Risch, Elizabeth J. van Rensburg, Michael Jones, Rikki Cannioto, Michelle A.T. Hildebrandt, Soo Hwang Teo, Fanny Dao, Susan J. Ramus, Sarah Colanna, Kathleen Claes, David G. Huntsman, Siel Olbrecht, Esther M. John, Robert A. Vierkant, Wendy K. Chung, Ellen L. Goode, Olufunmilayo I. Olopade, Evgeny N. Imyanitov, Joe Dennis, Andrew Berchuck, Banu Arun, Darcy L. Thull, Lian Li, Celeste Leigh Pearce, Sue K. Park, Susan M. Domchek, Agnieszka Budzilowska, Håkan Olsson, Susanne K. Kjaer, Mark H. Greene, Katia M. Zavaglia, Jolanta Kupryjanczyk, Nicolas Wentzensen, Karen H. Lu, Hayley Cassingham, Christopher A. Haiman, Eric Hahnen, Els Van Nieuwenhuysen, Katherine L. Nathanson, Anna deFazio, Ian G. Campbell, Paul A. James, Sara H. Olson, Eva Machackova, Anne M. van Altena, Irene L. Andrulis, Linda S. Cook, Matthias Dürst, Mary B. Daly, John R. McLaughlin, Niclas Håkansson, Jingmei Li, Diana Torres, Iain A. McNeish, Jennifer T. Loud, Roger L. Milne, Marta Santamariña, Annelie Augustinsson, Nhu D. Le, Kate Lawrenson, Kirsten B. Moysich, Dareng, Eileen O [0000-0003-0802-419X], Tyrer, Jonathan [0000-0003-3724-4757], Barnes, Daniel [0000-0002-3781-7570], Jones, Michelle R [0000-0001-5466-3844], Agata, Simona [0000-0002-6329-0768], Anton-Culver, Hoda [0000-0002-9603-0110], Augustinsson, Annelie [0000-0003-3415-0536], Bandera, Elisa V [0000-0002-8789-2755], Barkardottir, Rosa B [0000-0003-0629-2772], Brenton, James [0000-0002-5738-6683], Campbell, Ian [0000-0002-7773-4155], Chen, Kexin [0000-0003-1010-8093], Chung, Wendy K [0000-0003-3438-5685], Claes, Kathleen BM [0000-0003-0841-7372], Devilee, Peter [0000-0002-8023-2009], Diez, Orland [0000-0001-7339-0570], Bois, Andreas du [0000-0002-8477-506X], Eccles, Diana M [0000-0002-9935-3169], Eliassen, Heather A [0000-0002-3961-6609], Ganz, Patricia A [0000-0002-1841-4143], Giles, Graham G [0000-0003-4946-9099], Glendon, Gord [0000-0001-8630-6673], Greene, Mark H [0000-0003-1852-9239], Hartman, Mikael [0000-0001-5726-9965], Heitz, Florian [0000-0002-2412-0352], Isaacs, Claudine [0000-0002-9646-1260], Janavicius, Ramunas [0000-0002-3773-8485], John, Esther M [0000-0003-3259-8003], Kang, Daehee [0000-0003-4031-5878], Karlan, Beth Y [0000-0002-9451-2933], Khusnutdinova, Elza [0000-0003-2987-3334], Kjaer, Susanne K [0000-0002-8347-1398], Manoukian, Siranoush [0000-0002-6034-7562], Matsuo, Keitaro [0000-0003-1761-6314], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Nikitina-Zake, Liene [0000-0003-2491-5187], Olbrecht, Siel [0000-0001-9452-5905], Olopade, Olufunmilayo I [0000-0002-9936-1599], Olson, Sara H [0000-0003-0182-2754], Papi, Laura [0000-0003-4552-9517], Park, Sue K [0000-0001-5002-9707], Parsons, Michael T [0000-0003-3242-8477], Permuth, Jennifer B [0000-0002-4726-9264], Peterlongo, Paolo [0000-0001-6951-6855], Radice, Paolo [0000-0001-6298-4111], Swerdlow, Anthony J [0000-0001-5550-4159], Toland, Amanda E [0000-0002-0271-1792], Webb, Penelope M [0000-0003-0733-5930], Weinberg, Clarice R [0000-0002-7713-8556], Weitzel, Jeffrey N [0000-0001-6714-092X], Winham, Stacey J [0000-0002-8492-9102], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Easton, Douglas [0000-0003-2444-3247], Ramus, Susan J [0000-0003-0005-7798], Chenevix-Trench, Georgia [0000-0002-1878-2587], and Apollo - University of Cambridge Repository
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Oncology ,medicine.medical_specialty ,45/61 ,45/43 ,Single-nucleotide polymorphism ,Logistic regression ,631/208/2489 ,03 medical and health sciences ,0302 clinical medicine ,Lasso (statistics) ,Internal medicine ,Genotype ,medicine ,SNP ,030304 developmental biology ,0303 health sciences ,business.industry ,Hazard ratio ,article ,Odds ratio ,631/208/721 ,medicine.disease ,3. Good health ,030220 oncology & carcinogenesis ,business ,Ovarian cancer ,692/499 - Abstract
Funder: Funding details are provided in the Supplementary Material, 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 ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. 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 ancestry; 1.14(95%CI:1.08���1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30���1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,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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- 2022
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