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. 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 Balleine & 343 others Elisa 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, Louise 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 B M Claes, J. Margriet Collée, Linda S. Cook, Fergus J. Couch, Angela Cox, Daniel Cramer, Simon S. Cross, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Francesca Damiola, Agnieszka Dansonka-Mieszkowska, Hatef Darabi, Miguel De La Hoya, Anna Defazio, Joseph Dennis, Peter Devilee, Ed M. Dicks, Orland Diez, Jennifer A. Doherty, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dörk, Isabel Dos Santos Silva, Andreas Du Bois, Martine Dumont, Alison M. Dunning, Mercedes Duran, Douglas F. Easton, Diana Eccles, Robert P. Edwards, Hans Ehrencrona, Bent Ejlertsen, Arif B. Ekici, Steve D. Ellis, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Lidia Feliubadalo, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Annette Fontaine, Stefano Fortuzzi, Florentia Fostira, Brooke L. Fridley, Tara Friebel, Eitan Friedman, Grace Friel, Debra Frost, Judy Garber, Montserrat García-Closas, Simon A. Gayther, Aleksandra Gentry-Maharaj, Anne Marie Gerdes, Graham G. Giles, Rosalind Glasspool, Gord Glendon, Andrew K. Godwin, Marc T. Goodman, Martin Gore, Mark H. Greene, Mervi Grip, Jacek Gronwald, Daphne Gschwantler Kaulich, Pascal Guénel, 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 K. Høgdall, Estrid Høgdall, Frans B L Hogervorst, John L. Hopper, Keith Humphreys, Tomasz Huzarski, Evgeny N. 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, Lambertus A. Kiemeney, Susanne K. Kjaer, Julia A. Knight, Jacoba P. Knol-Bout, Irene Konstantopoulou, Veli Matti Kosma, Camilla Krakstad, Vessela Kristensen, Karoline B. Kuchenbaecker, Jolanta Kupryjanczyk, Yael Laitman, Diether Lambrechts, Sandrina Lambrechts, Melissa C. Larson, Adriana Lasa, Pierre Laurent-Puig, Conxi Lazaro, Nhu D. 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, Galina 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 McNeish, Alfons Meindl, Florence Menegaux, Primitiva Menéndez, Janusz Menkiszak, Usha Menon, Arjen R. Mensenkamp, Nicola Miller, Roger L. Milne, Francesmary Modugno, Marco Montagna, Kirsten B. Moysich, Heiko Müller, Anna Marie Mulligan, Taru A. Muranen, Steven 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 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 R. Rebbeck, Malcolm W R Reed, Gad Rennert, Harvey A. Risch, Mark Robson, Gustavo C. Rodriguez, Atocha Romero, Mary Anne Rossing, Joseph H. Rothstein, Anja Rudolph, Ingo Runnebaum, Ritu Salani, Helga B. Salvesen, Elinor J. Sawyer, Joellen M. Schildkraut, Marjanka K. Schmidt, Rita K. Schmutzler, Andreas Schneeweiss, Minouk J. Schoemaker, Michael G. Schrauder, Fredrick Schumacher, Ira Schwaab, Giulietta Scuvera, Thomas A. Sellers, Gianluca Severi, Caroline M. 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 C. Southey, Christa Stegmaier, Dominique Stoppa-Lyonnet, Lara Sucheston, Anthony 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 Ewart Toland, Rob A E M Tollenaar, Ian Tomlinson, Diana Torres, Thérèse Truong, Helen Tsimiklis, Nadine Tung, Shelley S. Tworoger, Jonathan P. Tyrer, Celine M. 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, Senno Verhoef, Robert A. Vierkant, Joseph Vijai, Allison F. Vitonis, Anna Von Wachenfeldt, Christine Walsh, Qin Wang, Shan Wang-Gohrke, Barbara Wappenschmidt, Maren Weischer, Jeffrey N. 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, Matti A. Rookus, Maartje J. Hooning, Ellen L. Goode, Cancer Family Register Breast Cancer Family Register, EMBRACE, Network GENICA Network, HEBON, SWE-BRCA

Research output: Contribution to journalReview article

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 (US)
Pages (from-to)386-401
Number of pages16
JournalGynecologic Oncology
Volume141
Issue number2
DOIs
StatePublished - May 1 2016
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Breast Neoplasms
Mutation
Survival
Genetic Testing
3' Untranslated Regions
MicroRNAs
Neoplasms
Binding Sites

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Hollestelle, A., Van Der Baan, F. H., Berchuck, A., Johnatty, S. E., Aben, K. K., Agnarsson, B. A., ... SWE-BRCA (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

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. / Hollestelle, Antoinette; Van Der Baan, Frederieke H.; Berchuck, Andrew; Johnatty, Sharon E.; Aben, Katja K.; Agnarsson, Bjarni A.; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K.; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V.; Barrowdale, Daniel; Bean, Yukie T.; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Brüning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H.; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Caligo, Maria A.; Campbell, Ian; Carter, Jonathan; Chang-Claude, Jenny; Chanock, Stephen J.; Claes, Kathleen B M; Collée, J. Margriet; Cook, Linda S.; Couch, Fergus J.; Cox, Angela; Cramer, Daniel; Cross, Simon S.; Cunningham, Julie M.; Cybulski, Cezary; Czene, Kamila; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; De La Hoya, Miguel; Defazio, Anna; Dennis, Joseph; Devilee, Peter; Dicks, Ed M.; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Silva, Isabel Dos Santos; Du Bois, Andreas; Dumont, Martine; Dunning, Alison M.; Duran, Mercedes; Easton, Douglas F.; Eccles, Diana; Edwards, Robert P.; Ehrencrona, Hans; Ejlertsen, Bent; Ekici, Arif B.; Ellis, Steve D.; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Fontaine, Annette; Fortuzzi, Stefano; Fostira, Florentia; Fridley, Brooke L.; Friebel, Tara; Friedman, Eitan; Friel, Grace; Frost, Debra; Garber, Judy; García-Closas, Montserrat; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Gerdes, Anne Marie; Giles, Graham G.; Glasspool, Rosalind; Glendon, Gord; Godwin, Andrew K.; Goodman, Marc T.; Gore, Martin; Greene, Mark H.; Grip, Mervi; Gronwald, Jacek; Gschwantler Kaulich, Daphne; Guénel, Pascal; Guzman, Starr R.; Haeberle, Lothar; Haiman, Christopher A.; Hall, Per; Halverson, Sandra L.; Hamann, Ute; Hansen, Thomas V O; Harter, Philipp; Hartikainen, Jaana M.; Healey, Sue; Hein, Alexander; Heitz, Florian; Henderson, Brian E.; Herzog, Josef; T Hildebrandt, Michelle A.; Høgdall, Claus K.; Høgdall, Estrid; Hogervorst, Frans B L; Hopper, John L.; Humphreys, Keith; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska, Katarzyna; Jensen, Allan; Jensen, Uffe Birk; Johnson, Nichola; Jukkola-Vuorinen, Arja; Kabisch, Maria; Karlan, Beth Y.; Kataja, Vesa; Kauff, Noah; Kelemen, Linda E.; Kerin, Michael J.; Kiemeney, Lambertus A.; Kjaer, Susanne K.; Knight, Julia A.; Knol-Bout, Jacoba P.; Konstantopoulou, Irene; Kosma, Veli Matti; Krakstad, Camilla; Kristensen, Vessela; Kuchenbaecker, Karoline B.; Kupryjanczyk, Jolanta; Laitman, Yael; Lambrechts, Diether; Lambrechts, Sandrina; Larson, Melissa C.; Lasa, Adriana; Laurent-Puig, Pierre; Lazaro, Conxi; Le, Nhu D.; Le Marchand, Loic; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Liang, Dong; Lindblom, Annika; Lindor, Noralane; Lissowska, Jolanta; Long, Jirong; Lu, Karen H.; Lubinski, Jan; Lundvall, Lene; Lurie, Galina; Mai, Phuong L.; Mannermaa, Arto; Margolin, Sara; Mariette, Frederique; Marme, Frederik; Martens, John W M; Massuger, Leon F A G; Maugard, Christine; Mazoyer, Sylvie; McGuffog, Lesley; McGuire, Valerie; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menegaux, Florence; Menéndez, Primitiva; Menkiszak, Janusz; Menon, Usha; Mensenkamp, Arjen R.; Miller, Nicola; Milne, Roger L.; Modugno, Francesmary; Montagna, Marco; Moysich, Kirsten B.; Müller, Heiko; Mulligan, Anna Marie; Muranen, Taru A.; Narod, Steven A.; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Finn C.; Nielsen, Sune F.; Nordestgaard, Børge G.; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olson, Sara H.; Oosterwijk, Jan C.; Orlow, Irene; Orr, Nick; Orsulic, Sandra; Osorio, Ana; Ottini, Laura; Paul, James; Pearce, Celeste L.; Pedersen, Inge Sokilde; Peissel, Bernard; Pejovic, Tanja; Pelttari, Liisa M.; Perkins, Jo; Permuth-Wey, Jenny; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Phillips, Kelly Anne; Piedmonte, Marion; Pike, Malcolm C.; Platte, Radka; Plisiecka-Halasa, Joanna; Poole, Elizabeth M.; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Ramus, Susan J.; Rebbeck, Timothy R.; Reed, Malcolm W R; Rennert, Gad; Risch, Harvey A.; Robson, Mark; Rodriguez, Gustavo C.; Romero, Atocha; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo; Salani, Ritu; Salvesen, Helga B.; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schrauder, Michael G.; Schumacher, Fredrick; Schwaab, Ira; Scuvera, Giulietta; Sellers, Thomas A.; Severi, Gianluca; Seynaeve, Caroline M.; Shah, Mitul; Shrubsole, Martha; Siddiqui, Nadeem; Sieh, Weiva; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Smeets, Dominiek; Sohn, Christof; Soller, Maria; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Sucheston, Lara; Swerdlow, Anthony; Tangen, Ingvild L.; Tea, Muy Kheng; Teixeira, Manuel R.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Thompson, Pamela J.; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda Ewart; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tsimiklis, Helen; Tung, Nadine; Tworoger, Shelley S.; Tyrer, Jonathan P.; Vachon, Celine M.; Van 't Veer, Laura J.; Van Altena, Anne M.; Van Asperen, C. J.; Van Den Berg, David; Van Den Ouweland, Ans M W; Van Doorn, Helena C.; Van Nieuwenhuysen, Els; Van Rensburg, Elizabeth J.; Vergote, Ignace; Verhoef, Senno; Vierkant, Robert A.; Vijai, Joseph; Vitonis, Allison F.; Von Wachenfeldt, Anna; Walsh, Christine; Wang, Qin; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weischer, Maren; Weitzel, Jeffrey N.; Weltens, Caroline; Wentzensen, Nicolas; Whittemore, Alice S.; Wilkens, Lynne R.; Winqvist, Robert; Wu, Anna H.; Wu, Xifeng; Yang, Hannah P.; Zaffaroni, Daniela; Pilar Zamora, M.; Zheng, Wei; Ziogas, Argyrios; Chenevix-Trench, Georgia; Pharoah, Paul D P; Rookus, Matti A.; Hooning, Maartje J.; Goode, Ellen L.; Breast Cancer Family Register, Cancer Family Register; EMBRACE; GENICA Network, Network; HEBON; SWE-BRCA.

In: Gynecologic Oncology, Vol. 141, No. 2, 01.05.2016, p. 386-401.

Research output: Contribution to journalReview article

Hollestelle, A, Van Der Baan, FH, Berchuck, A, Johnatty, SE, Aben, KK, Agnarsson, BA, Aittomäki, K, Alducci, E, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Antoniou, AC, Apicella, C, Arndt, V, Arnold, N, Arun, BK, Arver, B, Ashworth, A, Baglietto, L, Balleine, R, Bandera, EV, Barrowdale, D, Bean, YT, Beckmann, L, Beckmann, MW, Benitez, J, Berger, A, Berger, R, Beuselinck, B, Bisogna, M, Bjorge, L, Blomqvist, C, Bogdanova, NV, Bojesen, A, Bojesen, SE, Bolla, MK, Bonanni, B, Brand, JS, Brauch, H, Brenner, H, Brinton, L, Brooks-Wilson, A, Bruinsma, F, Brunet, J, Brüning, T, Budzilowska, A, Bunker, CH, Burwinkel, B, Butzow, R, Buys, SS, Caligo, MA, Campbell, I, Carter, J, Chang-Claude, J, Chanock, SJ, Claes, KBM, Collée, JM, Cook, LS, Couch, FJ, Cox, A, Cramer, D, Cross, SS, Cunningham, JM, Cybulski, C, Czene, K, Damiola, F, Dansonka-Mieszkowska, A, Darabi, H, De La Hoya, M, Defazio, A, Dennis, J, Devilee, P, Dicks, EM, Diez, O, Doherty, JA, Domchek, SM, Dorfling, CM, Dörk, T, Silva, IDS, Du Bois, A, Dumont, M, Dunning, AM, Duran, M, Easton, DF, Eccles, D, Edwards, RP, Ehrencrona, H, Ejlertsen, B, Ekici, AB, Ellis, SD, Engel, C, Eriksson, M, Fasching, PA, Feliubadalo, L, Figueroa, J, Flesch-Janys, D, Fletcher, O, Fontaine, A, Fortuzzi, S, Fostira, F, Fridley, BL, Friebel, T, Friedman, E, Friel, G, Frost, D, Garber, J, García-Closas, M, Gayther, SA, Gentry-Maharaj, A, Gerdes, AM, Giles, GG, Glasspool, R, Glendon, G, Godwin, AK, Goodman, MT, Gore, M, Greene, MH, Grip, M, Gronwald, J, Gschwantler Kaulich, D, Guénel, P, Guzman, SR, Haeberle, L, Haiman, CA, Hall, P, Halverson, SL, Hamann, U, Hansen, TVO, Harter, P, Hartikainen, JM, Healey, S, Hein, A, Heitz, F, Henderson, BE, Herzog, J, T Hildebrandt, MA, Høgdall, CK, Høgdall, E, Hogervorst, FBL, Hopper, JL, Humphreys, K, Huzarski, T, Imyanitov, EN, Isaacs, C, Jakubowska, A, Janavicius, R, Jaworska, K, Jensen, A, Jensen, UB, Johnson, N, Jukkola-Vuorinen, A, Kabisch, M, Karlan, BY, Kataja, V, Kauff, N, Kelemen, LE, Kerin, MJ, Kiemeney, LA, Kjaer, SK, Knight, JA, Knol-Bout, JP, Konstantopoulou, I, Kosma, VM, Krakstad, C, Kristensen, V, Kuchenbaecker, KB, Kupryjanczyk, J, Laitman, Y, Lambrechts, D, Lambrechts, S, Larson, MC, Lasa, A, Laurent-Puig, P, Lazaro, C, Le, ND, Le Marchand, L, Leminen, A, Lester, J, Levine, DA, Li, J, Liang, D, Lindblom, A, Lindor, N, Lissowska, J, Long, J, Lu, KH, Lubinski, J, Lundvall, L, Lurie, G, Mai, PL, Mannermaa, A, Margolin, S, Mariette, F, Marme, F, Martens, JWM, Massuger, LFAG, Maugard, C, Mazoyer, S, McGuffog, L, McGuire, V, McLean, C, McNeish, I, Meindl, A, Menegaux, F, Menéndez, P, Menkiszak, J, Menon, U, Mensenkamp, AR, Miller, N, Milne, RL, Modugno, F, Montagna, M, Moysich, KB, Müller, H, Mulligan, AM, Muranen, TA, Narod, SA, Nathanson, KL, Ness, RB, Neuhausen, SL, Nevanlinna, H, Neven, P, Nielsen, FC, Nielsen, SF, Nordestgaard, BG, Nussbaum, RL, Odunsi, K, Offit, K, Olah, E, Olopade, OI, Olson, JE, Olson, SH, Oosterwijk, JC, Orlow, I, Orr, N, Orsulic, S, Osorio, A, Ottini, L, Paul, J, Pearce, CL, Pedersen, IS, Peissel, B, Pejovic, T, Pelttari, LM, Perkins, J, Permuth-Wey, J, Peterlongo, P, Peto, J, Phelan, CM, Phillips, KA, Piedmonte, M, Pike, MC, Platte, R, Plisiecka-Halasa, J, Poole, EM, Poppe, B, Pylkäs, K, Radice, P, Ramus, SJ, Rebbeck, TR, Reed, MWR, Rennert, G, Risch, HA, Robson, M, Rodriguez, GC, Romero, A, Rossing, MA, Rothstein, JH, Rudolph, A, Runnebaum, I, Salani, R, Salvesen, HB, Sawyer, EJ, Schildkraut, JM, Schmidt, MK, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schrauder, MG, Schumacher, F, Schwaab, I, Scuvera, G, Sellers, TA, Severi, G, Seynaeve, CM, Shah, M, Shrubsole, M, Siddiqui, N, Sieh, W, Simard, J, Singer, CF, Sinilnikova, OM, Smeets, D, Sohn, C, Soller, M, Song, H, Soucy, P, Southey, MC, Stegmaier, C, Stoppa-Lyonnet, D, Sucheston, L, Swerdlow, A, Tangen, IL, Tea, MK, Teixeira, MR, Terry, KL, Terry, MB, Thomassen, M, Thompson, PJ, Tihomirova, L, Tischkowitz, M, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Torres, D, Truong, T, Tsimiklis, H, Tung, N, Tworoger, SS, Tyrer, JP, Vachon, CM, Van 't Veer, LJ, Van Altena, AM, Van Asperen, CJ, Van Den Berg, D, Van Den Ouweland, AMW, Van Doorn, HC, Van Nieuwenhuysen, E, Van Rensburg, EJ, Vergote, I, Verhoef, S, Vierkant, RA, Vijai, J, Vitonis, AF, Von Wachenfeldt, A, Walsh, C, Wang, Q, Wang-Gohrke, S, Wappenschmidt, B, Weischer, M, Weitzel, JN, Weltens, C, Wentzensen, N, Whittemore, AS, Wilkens, LR, Winqvist, R, Wu, AH, Wu, X, Yang, HP, Zaffaroni, D, Pilar Zamora, M, Zheng, W, Ziogas, A, Chenevix-Trench, G, Pharoah, PDP, Rookus, MA, Hooning, MJ, Goode, EL, Breast Cancer Family Register, CFR, EMBRACE, GENICA Network, N, HEBON & SWE-BRCA 2016, 'No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer', Gynecologic Oncology, vol. 141, no. 2, pp. 386-401. https://doi.org/10.1016/j.ygyno.2015.04.034
Hollestelle A, Van Der Baan FH, Berchuck A, Johnatty SE, Aben KK, Agnarsson BA et al. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology. 2016 May 1;141(2):386-401. https://doi.org/10.1016/j.ygyno.2015.04.034
Hollestelle, Antoinette ; Van Der Baan, Frederieke H. ; Berchuck, Andrew ; Johnatty, Sharon E. ; Aben, Katja K. ; Agnarsson, Bjarni A. ; Aittomäki, Kristiina ; Alducci, Elisa ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Antonenkova, Natalia N. ; Antoniou, Antonis C. ; Apicella, Carmel ; Arndt, Volker ; Arnold, Norbert ; Arun, Banu K. ; Arver, Brita ; Ashworth, Alan ; Baglietto, Laura ; Balleine, Rosemary ; Bandera, Elisa V. ; Barrowdale, Daniel ; Bean, Yukie T. ; Beckmann, Lars ; Beckmann, Matthias W. ; Benitez, Javier ; Berger, Andreas ; Berger, Raanan ; Beuselinck, Benoit ; Bisogna, Maria ; Bjorge, Line ; Blomqvist, Carl ; Bogdanova, Natalia V. ; Bojesen, Anders ; Bojesen, Stig E. ; Bolla, Manjeet K. ; Bonanni, Bernardo ; Brand, Judith S. ; Brauch, Hiltrud ; Brenner, Hermann ; Brinton, Louise ; Brooks-Wilson, Angela ; Bruinsma, Fiona ; Brunet, Joan ; Brüning, Thomas ; Budzilowska, Agnieszka ; Bunker, Clareann H. ; Burwinkel, Barbara ; Butzow, Ralf ; Buys, Saundra S. ; Caligo, Maria A. ; Campbell, Ian ; Carter, Jonathan ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Claes, Kathleen B M ; Collée, J. Margriet ; Cook, Linda S. ; Couch, Fergus J. ; Cox, Angela ; Cramer, Daniel ; Cross, Simon S. ; Cunningham, Julie M. ; Cybulski, Cezary ; Czene, Kamila ; Damiola, Francesca ; Dansonka-Mieszkowska, Agnieszka ; Darabi, Hatef ; De La Hoya, Miguel ; Defazio, Anna ; Dennis, Joseph ; Devilee, Peter ; Dicks, Ed M. ; Diez, Orland ; Doherty, Jennifer A. ; Domchek, Susan M. ; Dorfling, Cecilia M. ; Dörk, Thilo ; Silva, Isabel Dos Santos ; Du Bois, Andreas ; Dumont, Martine ; Dunning, Alison M. ; Duran, Mercedes ; Easton, Douglas F. ; Eccles, Diana ; Edwards, Robert P. ; Ehrencrona, Hans ; Ejlertsen, Bent ; Ekici, Arif B. ; Ellis, Steve D. ; Engel, Christoph ; Eriksson, Mikael ; Fasching, Peter A. ; Feliubadalo, Lidia ; Figueroa, Jonine ; Flesch-Janys, Dieter ; Fletcher, Olivia ; Fontaine, Annette ; Fortuzzi, Stefano ; Fostira, Florentia ; Fridley, Brooke L. ; Friebel, Tara ; Friedman, Eitan ; Friel, Grace ; Frost, Debra ; Garber, Judy ; García-Closas, Montserrat ; Gayther, Simon A. ; Gentry-Maharaj, Aleksandra ; Gerdes, Anne Marie ; Giles, Graham G. ; Glasspool, Rosalind ; Glendon, Gord ; Godwin, Andrew K. ; Goodman, Marc T. ; Gore, Martin ; Greene, Mark H. ; Grip, Mervi ; Gronwald, Jacek ; Gschwantler Kaulich, Daphne ; Guénel, Pascal ; Guzman, Starr R. ; Haeberle, Lothar ; Haiman, Christopher A. ; Hall, Per ; Halverson, Sandra L. ; Hamann, Ute ; Hansen, Thomas V O ; Harter, Philipp ; Hartikainen, Jaana M. ; Healey, Sue ; Hein, Alexander ; Heitz, Florian ; Henderson, Brian E. ; Herzog, Josef ; T Hildebrandt, Michelle A. ; Høgdall, Claus K. ; Høgdall, Estrid ; Hogervorst, Frans B L ; Hopper, John L. ; Humphreys, Keith ; Huzarski, Tomasz ; Imyanitov, Evgeny N. ; Isaacs, Claudine ; Jakubowska, Anna ; Janavicius, Ramunas ; Jaworska, Katarzyna ; Jensen, Allan ; Jensen, Uffe Birk ; Johnson, Nichola ; Jukkola-Vuorinen, Arja ; Kabisch, Maria ; Karlan, Beth Y. ; Kataja, Vesa ; Kauff, Noah ; Kelemen, Linda E. ; Kerin, Michael J. ; Kiemeney, Lambertus A. ; Kjaer, Susanne K. ; Knight, Julia A. ; Knol-Bout, Jacoba P. ; Konstantopoulou, Irene ; Kosma, Veli Matti ; Krakstad, Camilla ; Kristensen, Vessela ; Kuchenbaecker, Karoline B. ; Kupryjanczyk, Jolanta ; Laitman, Yael ; Lambrechts, Diether ; Lambrechts, Sandrina ; Larson, Melissa C. ; Lasa, Adriana ; Laurent-Puig, Pierre ; Lazaro, Conxi ; Le, Nhu D. ; Le Marchand, Loic ; Leminen, Arto ; Lester, Jenny ; Levine, Douglas A. ; Li, Jingmei ; Liang, Dong ; Lindblom, Annika ; Lindor, Noralane ; Lissowska, Jolanta ; Long, Jirong ; Lu, Karen H. ; Lubinski, Jan ; Lundvall, Lene ; Lurie, Galina ; Mai, Phuong L. ; Mannermaa, Arto ; Margolin, Sara ; Mariette, Frederique ; Marme, Frederik ; Martens, John W M ; Massuger, Leon F A G ; Maugard, Christine ; Mazoyer, Sylvie ; McGuffog, Lesley ; McGuire, Valerie ; McLean, Catriona ; McNeish, Iain ; Meindl, Alfons ; Menegaux, Florence ; Menéndez, Primitiva ; Menkiszak, Janusz ; Menon, Usha ; Mensenkamp, Arjen R. ; Miller, Nicola ; Milne, Roger L. ; Modugno, Francesmary ; Montagna, Marco ; Moysich, Kirsten B. ; Müller, Heiko ; Mulligan, Anna Marie ; Muranen, Taru A. ; Narod, Steven A. ; Nathanson, Katherine L. ; Ness, Roberta B. ; Neuhausen, Susan L. ; Nevanlinna, Heli ; Neven, Patrick ; Nielsen, Finn C. ; Nielsen, Sune F. ; Nordestgaard, Børge G. ; Nussbaum, Robert L. ; Odunsi, Kunle ; Offit, Kenneth ; Olah, Edith ; Olopade, Olufunmilayo I. ; Olson, Janet E. ; Olson, Sara H. ; Oosterwijk, Jan C. ; Orlow, Irene ; Orr, Nick ; Orsulic, Sandra ; Osorio, Ana ; Ottini, Laura ; Paul, James ; Pearce, Celeste L. ; Pedersen, Inge Sokilde ; Peissel, Bernard ; Pejovic, Tanja ; Pelttari, Liisa M. ; Perkins, Jo ; Permuth-Wey, Jenny ; Peterlongo, Paolo ; Peto, Julian ; Phelan, Catherine M. ; Phillips, Kelly Anne ; Piedmonte, Marion ; Pike, Malcolm C. ; Platte, Radka ; Plisiecka-Halasa, Joanna ; Poole, Elizabeth M. ; Poppe, Bruce ; Pylkäs, Katri ; Radice, Paolo ; Ramus, Susan J. ; Rebbeck, Timothy R. ; Reed, Malcolm W R ; Rennert, Gad ; Risch, Harvey A. ; Robson, Mark ; Rodriguez, Gustavo C. ; Romero, Atocha ; Rossing, Mary Anne ; Rothstein, Joseph H. ; Rudolph, Anja ; Runnebaum, Ingo ; Salani, Ritu ; Salvesen, Helga B. ; Sawyer, Elinor J. ; Schildkraut, Joellen M. ; Schmidt, Marjanka K. ; Schmutzler, Rita K. ; Schneeweiss, Andreas ; Schoemaker, Minouk J. ; Schrauder, Michael G. ; Schumacher, Fredrick ; Schwaab, Ira ; Scuvera, Giulietta ; Sellers, Thomas A. ; Severi, Gianluca ; Seynaeve, Caroline M. ; Shah, Mitul ; Shrubsole, Martha ; Siddiqui, Nadeem ; Sieh, Weiva ; Simard, Jacques ; Singer, Christian F. ; Sinilnikova, Olga M. ; Smeets, Dominiek ; Sohn, Christof ; Soller, Maria ; Song, Honglin ; Soucy, Penny ; Southey, Melissa C. ; Stegmaier, Christa ; Stoppa-Lyonnet, Dominique ; Sucheston, Lara ; Swerdlow, Anthony ; Tangen, Ingvild L. ; Tea, Muy Kheng ; Teixeira, Manuel R. ; Terry, Kathryn L. ; Terry, Mary Beth ; Thomassen, Mads ; Thompson, Pamela J. ; Tihomirova, Laima ; Tischkowitz, Marc ; Toland, Amanda Ewart ; Tollenaar, Rob A E M ; Tomlinson, Ian ; Torres, Diana ; Truong, Thérèse ; Tsimiklis, Helen ; Tung, Nadine ; Tworoger, Shelley S. ; Tyrer, Jonathan P. ; Vachon, Celine M. ; Van 't Veer, Laura J. ; Van Altena, Anne M. ; Van Asperen, C. J. ; Van Den Berg, David ; Van Den Ouweland, Ans M W ; Van Doorn, Helena C. ; Van Nieuwenhuysen, Els ; Van Rensburg, Elizabeth J. ; Vergote, Ignace ; Verhoef, Senno ; Vierkant, Robert A. ; Vijai, Joseph ; Vitonis, Allison F. ; Von Wachenfeldt, Anna ; Walsh, Christine ; Wang, Qin ; Wang-Gohrke, Shan ; Wappenschmidt, Barbara ; Weischer, Maren ; Weitzel, Jeffrey N. ; Weltens, Caroline ; Wentzensen, Nicolas ; Whittemore, Alice S. ; Wilkens, Lynne R. ; Winqvist, Robert ; Wu, Anna H. ; Wu, Xifeng ; Yang, Hannah P. ; Zaffaroni, Daniela ; Pilar Zamora, M. ; Zheng, Wei ; Ziogas, Argyrios ; Chenevix-Trench, Georgia ; Pharoah, Paul D P ; Rookus, Matti A. ; Hooning, Maartje J. ; Goode, Ellen L. ; Breast Cancer Family Register, Cancer Family Register ; EMBRACE ; GENICA Network, Network ; HEBON ; SWE-BRCA. / No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. In: Gynecologic Oncology. 2016 ; Vol. 141, No. 2. pp. 386-401.
@article{aae82852d65e45dba202bf18492fc5f2,
title = "No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer",
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.",
keywords = "Breast cancer, Clinical outcome, Genetic association, KRAS variant, Ovarian cancer",
author = "Antoinette Hollestelle and {Van Der Baan}, {Frederieke H.} and Andrew Berchuck and Johnatty, {Sharon E.} and Aben, {Katja K.} and Agnarsson, {Bjarni A.} and Kristiina Aittom{\"a}ki and Elisa Alducci and Andrulis, {Irene L.} and Hoda Anton-Culver and Antonenkova, {Natalia N.} and Antoniou, {Antonis C.} and Carmel Apicella and Volker Arndt and Norbert Arnold and Arun, {Banu K.} and Brita Arver and Alan Ashworth and Laura Baglietto and Rosemary Balleine and Bandera, {Elisa V.} and Daniel Barrowdale and Bean, {Yukie T.} and Lars Beckmann and Beckmann, {Matthias W.} and Javier Benitez and Andreas Berger and Raanan Berger and Benoit Beuselinck and Maria Bisogna and Line Bjorge and Carl Blomqvist and Bogdanova, {Natalia V.} and Anders Bojesen and Bojesen, {Stig E.} and Bolla, {Manjeet K.} and Bernardo Bonanni and Brand, {Judith S.} and Hiltrud Brauch and Hermann Brenner and Louise Brinton and Angela Brooks-Wilson and Fiona Bruinsma and Joan Brunet and Thomas Br{\"u}ning and Agnieszka Budzilowska and Bunker, {Clareann H.} and Barbara Burwinkel and Ralf Butzow and Buys, {Saundra S.} and Caligo, {Maria A.} and Ian Campbell and Jonathan Carter and Jenny Chang-Claude and Chanock, {Stephen J.} and Claes, {Kathleen B M} and Coll{\'e}e, {J. Margriet} and Cook, {Linda S.} and Couch, {Fergus J.} and Angela Cox and Daniel Cramer and Cross, {Simon S.} and Cunningham, {Julie M.} and Cezary Cybulski and Kamila Czene and Francesca Damiola and Agnieszka Dansonka-Mieszkowska and Hatef Darabi and {De La Hoya}, Miguel and Anna Defazio and Joseph Dennis and Peter Devilee and Dicks, {Ed M.} and Orland Diez and Doherty, {Jennifer A.} and Domchek, {Susan M.} and Dorfling, {Cecilia M.} and Thilo D{\"o}rk and Silva, {Isabel Dos Santos} and {Du Bois}, Andreas and Martine Dumont and Dunning, {Alison M.} and Mercedes Duran and Easton, {Douglas F.} and Diana Eccles and Edwards, {Robert P.} and Hans Ehrencrona and Bent Ejlertsen and Ekici, {Arif B.} and Ellis, {Steve D.} and Christoph Engel and Mikael Eriksson and Fasching, {Peter A.} and Lidia Feliubadalo and Jonine Figueroa and Dieter Flesch-Janys and Olivia Fletcher and Annette Fontaine and Stefano Fortuzzi and Florentia Fostira and Fridley, {Brooke L.} and Tara Friebel and Eitan Friedman and Grace Friel and Debra Frost and Judy Garber and Montserrat Garc{\'i}a-Closas and Gayther, {Simon A.} and Aleksandra Gentry-Maharaj and Gerdes, {Anne Marie} and Giles, {Graham G.} and Rosalind Glasspool and Gord Glendon and Godwin, {Andrew K.} and Goodman, {Marc T.} and Martin Gore and Greene, {Mark H.} and Mervi Grip and Jacek Gronwald and {Gschwantler Kaulich}, Daphne and Pascal Gu{\'e}nel and Guzman, {Starr R.} and Lothar Haeberle and Haiman, {Christopher A.} and Per Hall and Halverson, {Sandra L.} and Ute Hamann and Hansen, {Thomas V O} and Philipp Harter and Hartikainen, {Jaana M.} and Sue Healey and Alexander Hein and Florian Heitz and Henderson, {Brian E.} and Josef Herzog and {T Hildebrandt}, {Michelle A.} and H{\o}gdall, {Claus K.} and Estrid H{\o}gdall and Hogervorst, {Frans B L} and Hopper, {John L.} and Keith Humphreys and Tomasz Huzarski and Imyanitov, {Evgeny N.} and Claudine Isaacs and Anna Jakubowska and Ramunas Janavicius and Katarzyna Jaworska and Allan Jensen and Jensen, {Uffe Birk} and Nichola Johnson and Arja Jukkola-Vuorinen and Maria Kabisch and Karlan, {Beth Y.} and Vesa Kataja and Noah Kauff and Kelemen, {Linda E.} and Kerin, {Michael J.} and Kiemeney, {Lambertus A.} and Kjaer, {Susanne K.} and Knight, {Julia A.} and Knol-Bout, {Jacoba P.} and Irene Konstantopoulou and Kosma, {Veli Matti} and Camilla Krakstad and Vessela Kristensen and Kuchenbaecker, {Karoline B.} and Jolanta Kupryjanczyk and Yael Laitman and Diether Lambrechts and Sandrina Lambrechts and Larson, {Melissa C.} and Adriana Lasa and Pierre Laurent-Puig and Conxi Lazaro and Le, {Nhu D.} and {Le Marchand}, Loic and Arto Leminen and Jenny Lester and Levine, {Douglas A.} and Jingmei Li and Dong Liang and Annika Lindblom and Noralane Lindor and Jolanta Lissowska and Jirong Long and Lu, {Karen H.} and Jan Lubinski and Lene Lundvall and Galina Lurie and Mai, {Phuong L.} and Arto Mannermaa and Sara Margolin and Frederique Mariette and Frederik Marme and Martens, {John W M} and Massuger, {Leon F A G} and Christine Maugard and Sylvie Mazoyer and Lesley McGuffog and Valerie McGuire and Catriona McLean and Iain McNeish and Alfons Meindl and Florence Menegaux and Primitiva Men{\'e}ndez and Janusz Menkiszak and Usha Menon and Mensenkamp, {Arjen R.} and Nicola Miller and Milne, {Roger L.} and Francesmary Modugno and Marco Montagna and Moysich, {Kirsten B.} and Heiko M{\"u}ller and Mulligan, {Anna Marie} and Muranen, {Taru A.} and Narod, {Steven A.} and Nathanson, {Katherine L.} and Ness, {Roberta B.} and Neuhausen, {Susan L.} and Heli Nevanlinna and Patrick Neven and Nielsen, {Finn C.} and Nielsen, {Sune F.} and Nordestgaard, {B{\o}rge G.} and Nussbaum, {Robert L.} and Kunle Odunsi and Kenneth Offit and Edith Olah and Olopade, {Olufunmilayo I.} and Olson, {Janet E.} and Olson, {Sara H.} and Oosterwijk, {Jan C.} and Irene Orlow and Nick Orr and Sandra Orsulic and Ana Osorio and Laura Ottini and James Paul and Pearce, {Celeste L.} and Pedersen, {Inge Sokilde} and Bernard Peissel and Tanja Pejovic and Pelttari, {Liisa M.} and Jo Perkins and Jenny Permuth-Wey and Paolo Peterlongo and Julian Peto and Phelan, {Catherine M.} and Phillips, {Kelly Anne} and Marion Piedmonte and Pike, {Malcolm C.} and Radka Platte and Joanna Plisiecka-Halasa and Poole, {Elizabeth M.} and Bruce Poppe and Katri Pylk{\"a}s and Paolo Radice and Ramus, {Susan J.} and Rebbeck, {Timothy R.} and Reed, {Malcolm W R} and Gad Rennert and Risch, {Harvey A.} and Mark Robson and Rodriguez, {Gustavo C.} and Atocha Romero and Rossing, {Mary Anne} and Rothstein, {Joseph H.} and Anja Rudolph and Ingo Runnebaum and Ritu Salani and Salvesen, {Helga B.} and Sawyer, {Elinor J.} and Schildkraut, {Joellen M.} and Schmidt, {Marjanka K.} and Schmutzler, {Rita K.} and Andreas Schneeweiss and Schoemaker, {Minouk J.} and Schrauder, {Michael G.} and Fredrick Schumacher and Ira Schwaab and Giulietta Scuvera and Sellers, {Thomas A.} and Gianluca Severi and Seynaeve, {Caroline M.} and Mitul Shah and Martha Shrubsole and Nadeem Siddiqui and Weiva Sieh and Jacques Simard and Singer, {Christian F.} and Sinilnikova, {Olga M.} and Dominiek Smeets and Christof Sohn and Maria Soller and Honglin Song and Penny Soucy and Southey, {Melissa C.} and Christa Stegmaier and Dominique Stoppa-Lyonnet and Lara Sucheston and Anthony Swerdlow and Tangen, {Ingvild L.} and Tea, {Muy Kheng} and Teixeira, {Manuel R.} and Terry, {Kathryn L.} and Terry, {Mary Beth} and Mads Thomassen and Thompson, {Pamela J.} and Laima Tihomirova and Marc Tischkowitz and Toland, {Amanda Ewart} and Tollenaar, {Rob A E M} and Ian Tomlinson and Diana Torres and Th{\'e}r{\`e}se Truong and Helen Tsimiklis and Nadine Tung and Tworoger, {Shelley S.} and Tyrer, {Jonathan P.} and Vachon, {Celine M.} and {Van 't Veer}, {Laura J.} and {Van Altena}, {Anne M.} and {Van Asperen}, {C. J.} and {Van Den Berg}, David and {Van Den Ouweland}, {Ans M W} and {Van Doorn}, {Helena C.} and {Van Nieuwenhuysen}, Els and {Van Rensburg}, {Elizabeth J.} and Ignace Vergote and Senno Verhoef and Vierkant, {Robert A.} and Joseph Vijai and Vitonis, {Allison F.} and {Von Wachenfeldt}, Anna and Christine Walsh and Qin Wang and Shan Wang-Gohrke and Barbara Wappenschmidt and Maren Weischer and Weitzel, {Jeffrey N.} and Caroline Weltens and Nicolas Wentzensen and Whittemore, {Alice S.} and Wilkens, {Lynne R.} and Robert Winqvist and Wu, {Anna H.} and Xifeng Wu and Yang, {Hannah P.} and Daniela Zaffaroni and {Pilar Zamora}, M. and Wei Zheng and Argyrios Ziogas and Georgia Chenevix-Trench and Pharoah, {Paul D P} and Rookus, {Matti A.} and Hooning, {Maartje J.} and Goode, {Ellen L.} and {Breast Cancer Family Register}, {Cancer Family Register} and EMBRACE and {GENICA Network}, Network and HEBON and SWE-BRCA",
year = "2016",
month = "5",
day = "1",
doi = "10.1016/j.ygyno.2015.04.034",
language = "English (US)",
volume = "141",
pages = "386--401",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

AU - Hollestelle, Antoinette

AU - Van Der Baan, Frederieke H.

AU - Berchuck, Andrew

AU - Johnatty, Sharon E.

AU - Aben, Katja K.

AU - Agnarsson, Bjarni A.

AU - Aittomäki, Kristiina

AU - Alducci, Elisa

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Antoniou, Antonis C.

AU - Apicella, Carmel

AU - Arndt, Volker

AU - Arnold, Norbert

AU - Arun, Banu K.

AU - Arver, Brita

AU - Ashworth, Alan

AU - Baglietto, Laura

AU - Balleine, Rosemary

AU - Bandera, Elisa V.

AU - Barrowdale, Daniel

AU - Bean, Yukie T.

AU - Beckmann, Lars

AU - Beckmann, Matthias W.

AU - Benitez, Javier

AU - Berger, Andreas

AU - Berger, Raanan

AU - Beuselinck, Benoit

AU - Bisogna, Maria

AU - Bjorge, Line

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Bojesen, Anders

AU - Bojesen, Stig E.

AU - Bolla, Manjeet K.

AU - Bonanni, Bernardo

AU - Brand, Judith S.

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Brinton, Louise

AU - Brooks-Wilson, Angela

AU - Bruinsma, Fiona

AU - Brunet, Joan

AU - Brüning, Thomas

AU - Budzilowska, Agnieszka

AU - Bunker, Clareann H.

AU - Burwinkel, Barbara

AU - Butzow, Ralf

AU - Buys, Saundra S.

AU - Caligo, Maria A.

AU - Campbell, Ian

AU - Carter, Jonathan

AU - Chang-Claude, Jenny

AU - Chanock, Stephen J.

AU - Claes, Kathleen B M

AU - Collée, J. Margriet

AU - Cook, Linda S.

AU - Couch, Fergus J.

AU - Cox, Angela

AU - Cramer, Daniel

AU - Cross, Simon S.

AU - Cunningham, Julie M.

AU - Cybulski, Cezary

AU - Czene, Kamila

AU - Damiola, Francesca

AU - Dansonka-Mieszkowska, Agnieszka

AU - Darabi, Hatef

AU - De La Hoya, Miguel

AU - Defazio, Anna

AU - Dennis, Joseph

AU - Devilee, Peter

AU - Dicks, Ed M.

AU - Diez, Orland

AU - Doherty, Jennifer A.

AU - Domchek, Susan M.

AU - Dorfling, Cecilia M.

AU - Dörk, Thilo

AU - Silva, Isabel Dos Santos

AU - Du Bois, Andreas

AU - Dumont, Martine

AU - Dunning, Alison M.

AU - Duran, Mercedes

AU - Easton, Douglas F.

AU - Eccles, Diana

AU - Edwards, Robert P.

AU - Ehrencrona, Hans

AU - Ejlertsen, Bent

AU - Ekici, Arif B.

AU - Ellis, Steve D.

AU - Engel, Christoph

AU - Eriksson, Mikael

AU - Fasching, Peter A.

AU - Feliubadalo, Lidia

AU - Figueroa, Jonine

AU - Flesch-Janys, Dieter

AU - Fletcher, Olivia

AU - Fontaine, Annette

AU - Fortuzzi, Stefano

AU - Fostira, Florentia

AU - Fridley, Brooke L.

AU - Friebel, Tara

AU - Friedman, Eitan

AU - Friel, Grace

AU - Frost, Debra

AU - Garber, Judy

AU - García-Closas, Montserrat

AU - Gayther, Simon A.

AU - Gentry-Maharaj, Aleksandra

AU - Gerdes, Anne Marie

AU - Giles, Graham G.

AU - Glasspool, Rosalind

AU - Glendon, Gord

AU - Godwin, Andrew K.

AU - Goodman, Marc T.

AU - Gore, Martin

AU - Greene, Mark H.

AU - Grip, Mervi

AU - Gronwald, Jacek

AU - Gschwantler Kaulich, Daphne

AU - Guénel, Pascal

AU - Guzman, Starr R.

AU - Haeberle, Lothar

AU - Haiman, Christopher A.

AU - Hall, Per

AU - Halverson, Sandra L.

AU - Hamann, Ute

AU - Hansen, Thomas V O

AU - Harter, Philipp

AU - Hartikainen, Jaana M.

AU - Healey, Sue

AU - Hein, Alexander

AU - Heitz, Florian

AU - Henderson, Brian E.

AU - Herzog, Josef

AU - T Hildebrandt, Michelle A.

AU - Høgdall, Claus K.

AU - Høgdall, Estrid

AU - Hogervorst, Frans B L

AU - Hopper, John L.

AU - Humphreys, Keith

AU - Huzarski, Tomasz

AU - Imyanitov, Evgeny N.

AU - Isaacs, Claudine

AU - Jakubowska, Anna

AU - Janavicius, Ramunas

AU - Jaworska, Katarzyna

AU - Jensen, Allan

AU - Jensen, Uffe Birk

AU - Johnson, Nichola

AU - Jukkola-Vuorinen, Arja

AU - Kabisch, Maria

AU - Karlan, Beth Y.

AU - Kataja, Vesa

AU - Kauff, Noah

AU - Kelemen, Linda E.

AU - Kerin, Michael J.

AU - Kiemeney, Lambertus A.

AU - Kjaer, Susanne K.

AU - Knight, Julia A.

AU - Knol-Bout, Jacoba P.

AU - Konstantopoulou, Irene

AU - Kosma, Veli Matti

AU - Krakstad, Camilla

AU - Kristensen, Vessela

AU - Kuchenbaecker, Karoline B.

AU - Kupryjanczyk, Jolanta

AU - Laitman, Yael

AU - Lambrechts, Diether

AU - Lambrechts, Sandrina

AU - Larson, Melissa C.

AU - Lasa, Adriana

AU - Laurent-Puig, Pierre

AU - Lazaro, Conxi

AU - Le, Nhu D.

AU - Le Marchand, Loic

AU - Leminen, Arto

AU - Lester, Jenny

AU - Levine, Douglas A.

AU - Li, Jingmei

AU - Liang, Dong

AU - Lindblom, Annika

AU - Lindor, Noralane

AU - Lissowska, Jolanta

AU - Long, Jirong

AU - Lu, Karen H.

AU - Lubinski, Jan

AU - Lundvall, Lene

AU - Lurie, Galina

AU - Mai, Phuong L.

AU - Mannermaa, Arto

AU - Margolin, Sara

AU - Mariette, Frederique

AU - Marme, Frederik

AU - Martens, John W M

AU - Massuger, Leon F A G

AU - Maugard, Christine

AU - Mazoyer, Sylvie

AU - McGuffog, Lesley

AU - McGuire, Valerie

AU - McLean, Catriona

AU - McNeish, Iain

AU - Meindl, Alfons

AU - Menegaux, Florence

AU - Menéndez, Primitiva

AU - Menkiszak, Janusz

AU - Menon, Usha

AU - Mensenkamp, Arjen R.

AU - Miller, Nicola

AU - Milne, Roger L.

AU - Modugno, Francesmary

AU - Montagna, Marco

AU - Moysich, Kirsten B.

AU - Müller, Heiko

AU - Mulligan, Anna Marie

AU - Muranen, Taru A.

AU - Narod, Steven A.

AU - Nathanson, Katherine L.

AU - Ness, Roberta B.

AU - Neuhausen, Susan L.

AU - Nevanlinna, Heli

AU - Neven, Patrick

AU - Nielsen, Finn C.

AU - Nielsen, Sune F.

AU - Nordestgaard, Børge G.

AU - Nussbaum, Robert L.

AU - Odunsi, Kunle

AU - Offit, Kenneth

AU - Olah, Edith

AU - Olopade, Olufunmilayo I.

AU - Olson, Janet E.

AU - Olson, Sara H.

AU - Oosterwijk, Jan C.

AU - Orlow, Irene

AU - Orr, Nick

AU - Orsulic, Sandra

AU - Osorio, Ana

AU - Ottini, Laura

AU - Paul, James

AU - Pearce, Celeste L.

AU - Pedersen, Inge Sokilde

AU - Peissel, Bernard

AU - Pejovic, Tanja

AU - Pelttari, Liisa M.

AU - Perkins, Jo

AU - Permuth-Wey, Jenny

AU - Peterlongo, Paolo

AU - Peto, Julian

AU - Phelan, Catherine M.

AU - Phillips, Kelly Anne

AU - Piedmonte, Marion

AU - Pike, Malcolm C.

AU - Platte, Radka

AU - Plisiecka-Halasa, Joanna

AU - Poole, Elizabeth M.

AU - Poppe, Bruce

AU - Pylkäs, Katri

AU - Radice, Paolo

AU - Ramus, Susan J.

AU - Rebbeck, Timothy R.

AU - Reed, Malcolm W R

AU - Rennert, Gad

AU - Risch, Harvey A.

AU - Robson, Mark

AU - Rodriguez, Gustavo C.

AU - Romero, Atocha

AU - Rossing, Mary Anne

AU - Rothstein, Joseph H.

AU - Rudolph, Anja

AU - Runnebaum, Ingo

AU - Salani, Ritu

AU - Salvesen, Helga B.

AU - Sawyer, Elinor J.

AU - Schildkraut, Joellen M.

AU - Schmidt, Marjanka K.

AU - Schmutzler, Rita K.

AU - Schneeweiss, Andreas

AU - Schoemaker, Minouk J.

AU - Schrauder, Michael G.

AU - Schumacher, Fredrick

AU - Schwaab, Ira

AU - Scuvera, Giulietta

AU - Sellers, Thomas A.

AU - Severi, Gianluca

AU - Seynaeve, Caroline M.

AU - Shah, Mitul

AU - Shrubsole, Martha

AU - Siddiqui, Nadeem

AU - Sieh, Weiva

AU - Simard, Jacques

AU - Singer, Christian F.

AU - Sinilnikova, Olga M.

AU - Smeets, Dominiek

AU - Sohn, Christof

AU - Soller, Maria

AU - Song, Honglin

AU - Soucy, Penny

AU - Southey, Melissa C.

AU - Stegmaier, Christa

AU - Stoppa-Lyonnet, Dominique

AU - Sucheston, Lara

AU - Swerdlow, Anthony

AU - Tangen, Ingvild L.

AU - Tea, Muy Kheng

AU - Teixeira, Manuel R.

AU - Terry, Kathryn L.

AU - Terry, Mary Beth

AU - Thomassen, Mads

AU - Thompson, Pamela J.

AU - Tihomirova, Laima

AU - Tischkowitz, Marc

AU - Toland, Amanda Ewart

AU - Tollenaar, Rob A E M

AU - Tomlinson, Ian

AU - Torres, Diana

AU - Truong, Thérèse

AU - Tsimiklis, Helen

AU - Tung, Nadine

AU - Tworoger, Shelley S.

AU - Tyrer, Jonathan P.

AU - Vachon, Celine M.

AU - Van 't Veer, Laura J.

AU - Van Altena, Anne M.

AU - Van Asperen, C. J.

AU - Van Den Berg, David

AU - Van Den Ouweland, Ans M W

AU - Van Doorn, Helena C.

AU - Van Nieuwenhuysen, Els

AU - Van Rensburg, Elizabeth J.

AU - Vergote, Ignace

AU - Verhoef, Senno

AU - Vierkant, Robert A.

AU - Vijai, Joseph

AU - Vitonis, Allison F.

AU - Von Wachenfeldt, Anna

AU - Walsh, Christine

AU - Wang, Qin

AU - Wang-Gohrke, Shan

AU - Wappenschmidt, Barbara

AU - Weischer, Maren

AU - Weitzel, Jeffrey N.

AU - Weltens, Caroline

AU - Wentzensen, Nicolas

AU - Whittemore, Alice S.

AU - Wilkens, Lynne R.

AU - Winqvist, Robert

AU - Wu, Anna H.

AU - Wu, Xifeng

AU - Yang, Hannah P.

AU - Zaffaroni, Daniela

AU - Pilar Zamora, M.

AU - Zheng, Wei

AU - Ziogas, Argyrios

AU - Chenevix-Trench, Georgia

AU - Pharoah, Paul D P

AU - Rookus, Matti A.

AU - Hooning, Maartje J.

AU - Goode, Ellen L.

AU - Breast Cancer Family Register, Cancer Family Register

AU - EMBRACE,

AU - GENICA Network, Network

AU - HEBON,

AU - SWE-BRCA,

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Clinical outcome

KW - Genetic association

KW - KRAS variant

KW - Ovarian cancer

UR - http://www.scopus.com/inward/record.url?scp=84964863805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964863805&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2015.04.034

DO - 10.1016/j.ygyno.2015.04.034

M3 - Review article

VL - 141

SP - 386

EP - 401

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -