Polygenic risk modeling for prediction of epithelial ovarian cancer risk

著者: Eileen Dareng, Jonathan P. Tyrer, Daniel R. Barnes, Michelle R. Jones, Xin Yang, Katja K. H. Aben, Muriel A. Adank, Simona Agata, Irene L. Andrulis, Hoda Anton‐Culver, Natalia Antonenkova, Gerasimos Aravantinos, Banu Arun, Annelie Augustinsson, Judith Balmañà, Elisa V. Bandera, Rósa B. Barkardóttir, Daniel Barrowdale, Matthias W. Beckmann, Alicia Beeghly‐Fadiel, Javier Benı́tez, Marina Bermisheva, Marcus Q. Bernardini, Line Bjørge, Amanda Black, Natalia Bogdanova, Bernardo Bonanni, Åke Borg, James D. Brenton, Agnieszka Budziłowska, Ralf Butzow, Saundra S. Buys, Hui Cai, Maria A. Caligo, Ian Campbell, Rikki Cannioto, Hayley Cassingham, Jenny Chang‐Claude, Stephen J. Chanock, Kexin Chen, Yoke-Eng Chiew, Wendy K. Chung, Kathleen Claes, Sarah V. Colonna, GEMO Study Collaborators, Fabienne Lesueur, Noura Mebirouk, GC-HBOC Study Collaborators, Christoph Engel, Rita K. Schmutzler, EMBRACE Collaborators, Daniel Barrowdale, Eleanor Davies, Diana M. Eccles, D. Gareth Evans, Linda S. Cook, Fergus J. Couch, Mary B. Daly, Fanny Dao, Eleanor Davies, Miguel de la Hoya, Robin De Putter, Joe Dennis, Allison DePersia, Peter Devilee, Orland Dı́ez, Yuan Chun Ding, Jennifer A. Doherty, Susan M. Domchek, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana M. Eccles, Heather Eliassen, Christoph Engel, D. Gareth Evans, Peter A. Fasching, James M. Flanagan, Renée T. Fortner, Eva Macháčková, Eitan Friedman, Patricia A. Ganz, Judy E. Garber, Francesca Gensini, Graham G. Giles, Gord Glendon, Andrew K. Godwin, Marc T. Goodman, Mark H. Greene, Jacek Gronwald, OPAL Study Group, AOCS Group, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Ute Hamann, Thomas V. O. Hansen, Holly R. Harris, Mikael Hartman, Florian Heitz, Michelle A. T. Hildebrandt, Estrid Høgdall, Claus Høgdall, John L. Hopper, Ruea‐Yea Huang, Chad D. Huff, Peter J. Hulick, David G. Huntsman, Evgeny N. Imyanitov, KConFab Investigators, Georgia Chenevix‐Trench, HEBON Investigators, Muriel A. Adank, Peter Devilee, Annemieke H. van der Hout, Claudine Isaacs, Anna Jakubowska, Paul A. James, Ramūnas Janavičius, Allan Jensen, Oskar T. Johannsson, Esther M. John, Michael E. Jones, Daehee Kang, Beth Y. Karlan, Anthony Karnezis, Linda E. Kelemen, Э. К. Хуснутдинова, Lambertus A. Kiemeney, Byoung‐Gie Kim, Susanne K. Kjaer, Ian K. Komenaka, Jolanta Kupryjańczyk, Allison W. Kurian, Ava Kwong, Diether Lambrechts, Melissa C. Larson, Conxi Lázaro, Nhu D. Le, Goska Leslie, Jenny Lester, Fabienne Lesueur, Douglas A. Levine, Jingmei Li, Jingmei Li, Jennifer T. Loud, Karen H. Lu, Jan Lubiński, Phuong L. Mai, Siranoush Manoukian, Jeffrey R. Marks, Rayna K. Matsuno, Keitaro Matsuo, Taymaa May, Lesley McGuffog, John R. McLaughlin, Iain A. McNeish, Noura Mebirouk, Usha Menon, Austin Miller, Roger L. Milne, Albina N. Minlikeeva, Francesmary Modugno, Marco Montagna, Kirsten B. Moysich, Elizabeth Munro, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Joanne Ngeow, Henriette Roed Nielsen, Finn Cilius Nielsen, Liene Nikitina-Zake, Kunle Odunsi, Kenneth Offit, Edith Oláh, Siel Olbrecht, Olufunmilayo I. Olopade, Sara H. Olson, Håkan Olsson, Ana Osorio, Laura Papi, Sue K. Park, Michael T. Parsons, Harsha Pathak, Inge Søkilde Pedersen, Ana Peixoto, Tanja Pejović, Pedro Perez-Segura, Jennifer B. Permuth, Beth Peshkin, Paolo Peterlongo, Anna Piskorz, Darya Prokofyeva, Paolo Radice, Johanna Rantala, Marjorie J. Riggan, Harvey A. Risch, Cristina Rodriguez-Antona, Eric A. Ross, Mary Anne Rossing, Ingo B. Runnebaum, Dale P. Sandler, Marta Santamariña, Penny Soucy, Rita K. Schmutzler, Veronica Wendy Setiawan, Kang Shan, Weiva Sieh, Jacques Simard, Christian F. Singer, Anna P. Sokolenko, Honglin Song, Melissa C. Southey, Helen Steed, Dominique Stoppa-Lyonnet, Rebecca Sutphen, Anthony J. Swerdlow, Yen Yen Tan, Manuel R. Teixeira, Soo‐Hwang Teo, Kathryn L. Terry, Mary Beth Terry, Eileen Dareng, Jonathan P. Tyrer, Michelle R. Jones, Katja K. H. Aben, Hoda Anton‐Culver, Natalia Antonenkova, Gerasimos Aravantinos, Matthias W. Beckmann, Alicia Beeghly‐Fadiel, Javier Benı́tez, Marina Bermisheva, Marcus Q. Bernardini, Line Bjørge, Natalia Bogdanova, James D. Brenton, Agnieszka Budziłowska, Ralf Butzow, Hui Cai, Ian Campbell, Rikki Cannioto, Jenny Chang‐Claude, Stephen J. Chanock, Kexin Chen, Yoke-Eng Chiew, Linda S. Cook, Fanny Dao, Joe Dennis, Jennifer A. Doherty, Thilo Dörk, Andreas du Bois, Matthias Dürst, Diana M. Eccles, Heather Eliassen, Peter A. Fasching, James M. Flanagan, Renée T. Fortner, Graham G. Giles, Marc T. Goodman, Jacek Gronwald, Christopher A. Haiman, Niclas Håkansson, Holly R. Harris, Florian Heitz, Michelle A. T. Hildebrandt, Estrid Høgdall, Claus Høgdall, Ruea‐Yea Huang, Chad D. Huff, David G. Huntsman, Anna Jakubowska, Allan Jensen, Michael E. Jones, Daehee Kang, Beth Y. Karlan, Anthony Karnezis, Linda E. Kelemen, Э. К. Хуснутдинова, Lambertus A. Kiemeney, Byoung‐Gie Kim, Susanne K. Kjaer, Jolanta Kupryjańczyk, Diether Lambrechts, Melissa C. Larson, Nhu D. Le, Jenny Lester, Douglas A. Levine, Karen H. Lu, Jan Lubiński, Jeffrey R. Marks, Rayna K. Matsuno, Keitaro Matsuo, Taymaa May, John R. McLaughlin, Iain A. McNeish, Roger L. Milne, Albina N. Minlikeeva, Francesmary Modugno, Kirsten B. Moysich, Elizabeth Munro, Heli Nevanlinna, Kunle Odunsi, Siel Olbrecht, Sara H. Olson, Håkan Olsson, Ana Osorio, Sue K. Park, Tanja Pejović, Jennifer B. Permuth, Anna Piskorz, Darya Prokofyeva, Marjorie J. Riggan, Harvey A. Risch, Cristina Rodriguez-Antona, Mary Anne Rossing, Ingo B. Runnebaum, Dale P. Sandler, Veronica Wendy Setiawan, Kang Shan, Weiva Sieh, Honglin Song, Melissa C. Southey, Helen Steed, Rebecca Sutphen, Anthony J. Swerdlow, Soo‐Hwang Teo, Kathryn L. Terry, Pamela J. Thompson, Liv Cecilie Vestrheim Thomsen, Linda Titus, Britton Trabert, Ruth C. Travis, Shelley S. Tworoger, Ellen Valen, Anne M. van Altena, Els Van Nieuwenhuysen, Digna Velez Edwards, Robert A. Vierkant, Frances Wang, Penelope M. Webb, Clarice R. Weinberg, Nicolas Wentzensen, Emily White, Alice S. Whittemore, Stacey J. Winham, Alicja Wolk, Yin Ling Woo, Anna H. Wu, Yan Li, Drakoulis Yannoukakos, Wei Zheng, Argyrios Ziogas, Kate Lawrenson, Anna DeFazio, Susan J. Ramus, Celeste Leigh Pearce, Alvaro N. Monteiro, Julie M. Cunningham, Ellen L. Goode, Joellen M. Schildkraut, Andrew Berchuck, Simon A. Gayther, Paul D. P. Pharoah, Daniel R. Barnes, Xin Yang, Muriel A. Adank, Simona Agata, Irene L. Andrulis, Banu Arun, Annelie Augustinsson, Judith Balmañà, Rósa B. Barkardóttir, Daniel Barrowdale, Bernardo Bonanni, Åke Borg, Saundra S. Buys, Maria A. Caligo, Hayley Cassingham, Wendy K. Chung, Kathleen Claes, Sarah V. Colonna, Fergus J. Couch, Mary B. Daly, Eleanor Davies, Miguel de la Hoya, Robin De Putter, Allison DePersia, Peter Devilee, Orland Dı́ez, Yuan Chun Ding, Susan M. Domchek, Diana M. Eccles, Christoph Engel, D. Gareth Evans, Eva Macháčková, Eitan Friedman, Patricia A. Ganz, Judy E. Garber, Francesca Gensini, Gord Glendon, Andrew K. Godwin, Mark H. Greene, Eric Hahnen, Ute Hamann, Thomas V. O. Hansen, Mikael Hartman, John L. Hopper, Peter J. Hulick, Evgeny N. Imyanitov, Claudine Isaacs, Paul A. James, Ramūnas Janavičius, Oskar T. Johannsson, Esther M. John, Ian K. Komenaka, Allison W. Kurian, Ava Kwong, Conxi Lázaro, Goska Leslie, Fabienne Lesueur, Jingmei Li, Jennifer T. Loud, Phuong L. Mai, Siranoush Manoukian, Lesley McGuffog, Noura Mebirouk, Austin Miller, Marco Montagna, Katherine L. Nathanson, Susan L. Neuhausen, Joanne Ngeow Yuen Yie, Henriette Roed Nielsen, Liene Nikitina-Zake, Kenneth Offit, Edith Oláh, Olufunmilayo I. Olopade, Laura Papi, Michael T. Parsons, Harsha Pathak, Inge Søkilde Pedersen, Ana Peixoto, Pedro Perez-Segura, Beth Peshkin, Paolo Peterlongo, Paolo Radice, Johanna Rantala, Eric A. Ross, Marta Santamariña, Penny Soucy, Rita K. Schmutzler, Jacques Simard, Christian F. Singer, Anna P. Sokolenko, Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R. Teixeira, Mary Beth Terry, Mads Thomassen, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Nadine Tung, Annemieke H. van der Hout, Elizabeth J. van Rensburg, Ana Vega, Barbara Wappenschmidt, Jeffrey N. Weitzel, Katia M. Zavaglia, Kristin K. Zorn, Thomas A. Sellers, Georgia Chenevix‐Trench, Antonis C. Antoniou, Mads Thomassen, Pamela J. Thompson, Liv Cecilie Vestrheim Thomsen, Darcy L. Thull, Marc Tischkowitz, Linda Titus, Amanda E. Toland, Diana Torres, Britton Trabert, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Ellen Valen, Anne M. van Altena, Annemieke H. van der Hout, Els Van Nieuwenhuysen, Elizabeth J. van Rensburg, Ana Vega, Digna Velez Edwards, Robert A. Vierkant, Frances Wang, Barbara Wappenschmidt, Penelope M. Webb, Clarice R. Weinberg, Jeffrey N. Weitzel, Nicolas Wentzensen, Emily White, Alice S. Whittemore, Stacey J. Winham, Alicja Wolk, Yin Ling Woo, Anna H. Wu, Yan Li, Drakoulis Yannoukakos, Katia M. Zavaglia, Wei Zheng, Argyrios Ziogas, Kristin K. Zorn, Zdeněk Kleibl, Douglas F. Easton, Kate Lawrenson, Anna DeFazio, Thomas A. Sellers, Susan J. Ramus, Celeste Leigh Pearce, Alvaro N. Monteiro, Julie M. Cunningham, Ellen L. Goode, Joellen M. Schildkraut, Andrew Berchuck, Georgia Chenevix‐Trench, Simon A. Gayther, Antonis C. Antoniou, Paul D. P. Pharoah - European Journal of Human Genetics 2022 被引用: 72

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.