No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

Antoinette Hollestelle, Frederieke H. Van Der Baan, Andrew Berchuck, Sharon E. Johnatty, Katja K H Aben, Bjarni A. Agnarsson, Kristiina Aittomäki, Elisa Alducci, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Antonis C. Antoniou, Carmel Apicella, Volker Arndt, Norbert Arnold, Banu K. Arun, Brita Arver, Alan Ashworth, Laura Baglietto, Rosemary BalleineElisa V. Bandera, Daniel Barrowdale, Yukie T. Bean, Lars Beckmann, Matthias W. Beckmann, Javier Benitez, Andreas Berger, Raanan Berger, Benoit Beuselinck, Maria Bisogna, Line Bjorge, Carl Blomqvist, Natalia V. Bogdanova, Anders Bojesen, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, L. A. Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Thomas Brüning, Agnieszka Budzilowska, Clareann H. Bunker, Barbara Burwinkel, Ralf Butzow, Saundra S. Buys, Maria A. Caligo, Ian Campbell, Jonathan Carter, Jenny Chang-Claude, Stephen J. Chanock, Kathleen Claes, J. Margriet Collée, Linda S. Cook, Fergus J. Couch, Angela Cox, Daniel W. Cramer, Simon S. Cross, Julie Cunningham, Cezary Cybulski, Kamila Czene, Francesca Damiola, Agnieszka Dansonka-Mieszkowska, Hatef Darabi, Miguel de la Hoya, A. deFazio, Joe Dennis, Peter Devilee, Ed Dicks, Orland Diez, Jennifer A. Doherty, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dörk, Isabel Dos Santos Silva, A. du Bois, Martine Dumont, Alison Dunning, Mercedes Durán, Douglas F. Easton, Diana Eccles, Robert P. Edwards, Hans Ehrencrona, Bent Ejlertsen, Arif B. Ekici, Steve Ellis, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Lidia Feliubadaló, Jonine D. Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Annette Fontaine, S. Fortuzzi, Florentia Fostira, Brooke L. Fridley, Tara M. Friebel, Eitan Friedman, Grace Friel, D. Frost, Judy E. Garber, Montse Garcia-Closas, Simon A. Gayther, Aleksandra Gentry-Maharaj, Anne Marie Gerdes, Graham Giles, Rosalind Glasspool, Gord Glendon, Andrew K. Godwin, Marc T. Goodman, M. E. Gore, Mark H. Greene, Mervi Grip, Jacek Gronwald, Daphne Gschwantler-Kaulich, Pascal Guenel, Starr R. Guzman, Lothar Haeberle, Christopher A. Haiman, Per Hall, Sandra L. Halverson, Ute Hamann, Thomas v O Hansen, Philipp Harter, Jaana M. Hartikainen, Sue Healey, Alexander Hein, Florian Heitz, Brian E. Henderson, Josef Herzog, Michelle A. T Hildebrandt, Claus Hogdall, Estrid Hogdall, Frans B. Hogervorst, John Hopper, Keith Humphreys, Tomasz Huzarski, Evgeny Imyanitov, Claudine Isaacs, Anna Jakubowska, Ramunas Janavicius, Katarzyna Jaworska, Allan Jensen, Uffe Birk Jensen, Nichola Johnson, Arja Jukkola-Vuorinen, Maria Kabisch, Beth Y. Karlan, Vesa Kataja, Noah Kauff, Linda E. Kelemen, Michael J. Kerin, Lambartus Kiemeney, Susanne Krüger Kjær, Julia A. Knight, Jacoba P. Knol-Bout, Irene Konstantopoulou, Veli Matti Kosma, Camilla Krakstad, Vessela Kristensen, Karoline Kuchenbaecker, Jolanta Kupryjanczyk, Yael Laitman, Diether Lambrechts, Sandrina Lambrechts, Melissa C. Larson, Adriana Lasa, Pierre Laurent-Puig, Conxi Lazaro, Nhu Le, Loic Le Marchand, Arto Leminen, Jenny Lester, Douglas A. Levine, Jingmei Li, Dong Liang, Annika Lindblom, Noralane Lindor, Jolanta Lissowska, Jirong Long, Karen H. Lu, Jan Lubinski, Lene Lundvall, G. Lurie, Phuong L. Mai, Arto Mannermaa, Sara Margolin, Frederique Mariette, Frederik Marme, John W M Martens, Leon F A G Massuger, Christine Maugard, Sylvie Mazoyer, Lesley McGuffog, Valerie McGuire, Catriona McLean, Iain A. McNeish, Alfons Meindl, Florence Menegaux, Primitiva Menéndez, Janusz Menkiszak, Usha Menon, Arjen Mensenkamp, Nicola Miller, Roger L. Milne, Francesmary Modugno, Marco Montagna, Kirsten B. Moysich, Heiko Müller, Anna Marie Mulligan, Taru A. Muranen, S. A. Narod, Katherine L. Nathanson, Roberta B. Ness, Susan L. Neuhausen, Heli Nevanlinna, Patrick Neven, Finn C. Nielsen, Sune F. Nielsen, Børge G. Nordestgaard, Robert L. Nussbaum, Kunle Odunsi, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Janet E. Olson, Sara H. Olson, Jan C. Oosterwijk, Irene Orlow, Nick Orr, Sandra Orsulic, Ana Osorio, Laura Ottini, James Paul, Celeste L. Pearce, Inge Sokilde Pedersen, Bernard Gilles Peissel, Tanja Pejovic, Liisa M. Pelttari, Jo Perkins, Jenny Permuth-Wey, Paolo Peterlongo, Julian Peto, Catherine M. Phelan, Kelly Anne Phillips, Marion Piedmonte, Malcolm C. Pike, Radka Platte, Joanna Plisiecka-Halasa, Elizabeth M. Poole, Bruce Poppe, Katri Pylkäs, Paolo Radice, Susan J. Ramus, Timothy Rebbeck, Malcolm W R Reed, Gad Rennert, Harvey A. Risch, Mark E. Robson, Gustavo C. Rodriguez, Atocha Romero, Mary Anne Rossing, Joseph H. Rothstein, Anja Rudolph, I. B. Runnebaum, Ritu Salani, Helga B. Salvesen, Elinor J. Sawyer, Joellen M. Schildkraut, Marjanka K. Schmidt, Rita K. Schmutzler, Andreas Schneeweiss, Minouk J. Schoemaker, Michael Schrauder, Fredrick Schumacher, Ira Schwaab, Giulietta Scuvera, Thomas A. Sellers, Gianluca Severi, Caroline Seynaeve, Mitul Shah, Martha Shrubsole, Nadeem Siddiqui, Weiva Sieh, Jacques Simard, Christian F. Singer, Olga M. Sinilnikova, Dominiek Smeets, Christof Sohn, Maria Soller, Honglin Song, Penny Soucy, Melissa Southey, Christa Stegmaier, Dominique Stoppa-Lyonnet, Lara Sucheston, Anthony J. Swerdlow, Ingvild L. Tangen, Muy Kheng Tea, Manuel R. Teixeira, Kathryn L. Terry, Mary Beth Terry, Mads Thomassen, Pamela J. Thompson, Laima Tihomirova, Marc Tischkowitz, Amanda E. Toland, Robert A E M Tollenaar, Ian P M Tomlinson, Diana Torres, Therese Truong, Helen Tsimiklis, Nadine Tung, Shelley S. Tworoger, Jonathan Tyrer, Celine Vachon, Laura J. Van 't Veer, Anne M. Van Altena, C. J. Van Asperen, David Van Den Berg, Ans M W Van Den Ouweland, Helena C. Van Doorn, Els Van Nieuwenhuysen, Elizabeth J. van Rensburg, Ignace Vergote, S. Verhoef, Robert A. Vierkant, Joseph Vijai, Allison F. Vitonis, Anna von Wachenfeldt, Christine S. Walsh, Qin Wang, Shan Wang-Gohrke, Barbara Wappenschmidt, Maren Weischer, Jeffrey Weitzel, Caroline Weltens, Nicolas Wentzensen, Alice S. Whittemore, Lynne R. Wilkens, Robert Winqvist, Anna H. Wu, Xifeng Wu, Hannah P. Yang, Daniela Zaffaroni, M. Pilar Zamora, Wei Zheng, Argyrios Ziogas, Georgia Chenevix-Trench, Paul D P Pharoah, M. A. Rookus, Maartje J. Hooning, Ellen L. Goode, Cancer Family Register Breast Cancer Family Register, [No Value] EMBRACE, Network GENICA Network, [No Value] HEBON, [No Value] SWE-BRCA

Research output: Contribution to journalArticle

Abstract

Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.

Original languageEnglish
Pages (from-to)386-401
Number of pages16
JournalGynecologic Oncology
Volume141
Issue number2
DOIs
Publication statusPublished - May 1 2016

Keywords

  • Breast cancer
  • Clinical outcome
  • Genetic association
  • KRAS variant
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

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    Hollestelle, A., Van Der Baan, F. H., Berchuck, A., Johnatty, S. E., Aben, K. K. H., Agnarsson, B. A., Aittomäki, K., Alducci, E., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Antoniou, A. C., Apicella, C., Arndt, V., Arnold, N., Arun, B. K., Arver, B., Ashworth, A., Baglietto, L., ... SWE-BRCA, N. V. (2016). No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology, 141(2), 386-401. https://doi.org/10.1016/j.ygyno.2015.04.034