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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. and Anton-Culver, Hoda, et al. (2016) In Gynecologic Oncology 141(2). p.386-401
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... (More)

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.

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published
subject
keywords
Breast cancer, Clinical outcome, Genetic association, KRAS variant, Ovarian cancer
in
Gynecologic Oncology
volume
141
issue
2
pages
16 pages
publisher
Academic Press
external identifiers
  • Scopus:84964863805
  • WOS:000375358200032
ISSN
0090-8258
DOI
10.1016/j.ygyno.2015.04.034
language
English
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yes
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1fcf3e9b-4a28-4551-b2de-36336041f24e
date added to LUP
2016-06-03 15:38:52
date last changed
2016-11-25 08:14:17
@misc{1fcf3e9b-4a28-4551-b2de-36336041f24e,
  abstract     = {<p>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.</p>},
  author       = {Hollestelle, Antoinette and Van Der Baan, Frederieke H. and Berchuck, Andrew and Johnatty, Sharon E. and Aben, Katja K. and Agnarsson, Bjarni A. and Aittomäki, Kristiina and Alducci, Elisa and Andrulis, Irene L. and Anton-Culver, Hoda and Antonenkova, Natalia N. and Antoniou, Antonis C. and Apicella, Carmel and Arndt, Volker and Arnold, Norbert and Arun, Banu K. and Arver, Brita and Ashworth, Alan and Baglietto, Laura and Balleine, Rosemary and Bandera, Elisa V. and Barrowdale, Daniel and Bean, Yukie T. and Beckmann, Lars and Beckmann, Matthias W. and Benitez, Javier and Berger, Andreas and Berger, Raanan and Beuselinck, Benoit and Bisogna, Maria and Bjorge, Line and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Anders and Bojesen, Stig E. and Bolla, Manjeet K. and Bonanni, Bernardo and Brand, Judith S. and Brauch, Hiltrud and Brenner, Hermann and Brinton, Louise and Brooks-Wilson, Angela and Bruinsma, Fiona and Brunet, Joan and Brüning, Thomas and Budzilowska, Agnieszka and Bunker, Clareann H. and Burwinkel, Barbara and Butzow, Ralf and Buys, Saundra S. and Caligo, Maria A. and Campbell, Ian and Carter, Jonathan and Chang-Claude, Jenny and Chanock, Stephen J. and Claes, Kathleen B M and Collée, J. Margriet and Cook, Linda S. and Couch, Fergus J. and Cox, Angela and Cramer, Daniel and Cross, Simon S. and Cunningham, Julie M. and Cybulski, Cezary and Czene, Kamila and Damiola, Francesca and Dansonka-Mieszkowska, Agnieszka and Darabi, Hatef and De La Hoya, Miguel and Defazio, Anna and Dennis, Joseph and Devilee, Peter and Dicks, Ed M. and Diez, Orland and Doherty, Jennifer A. and Domchek, Susan M. and Dorfling, Cecilia M. and Dörk, Thilo and Silva, Isabel Dos Santos and Du Bois, Andreas and Dumont, Martine and Dunning, Alison M. and Duran, Mercedes and Easton, Douglas F. and Eccles, Diana and Edwards, Robert P. and Ehrencrona, Hans and Ejlertsen, Bent and Ekici, Arif B. and Ellis, Steve D. and Engel, Christoph and Eriksson, Mikael and Fasching, Peter A. and Feliubadalo, Lidia and Figueroa, Jonine and Flesch-Janys, Dieter and Fletcher, Olivia and Fontaine, Annette and Fortuzzi, Stefano and Fostira, Florentia and Fridley, Brooke L. and Friebel, Tara and Friedman, Eitan and Friel, Grace and Frost, Debra and Garber, Judy and García-Closas, Montserrat and Gayther, Simon A. and Gentry-Maharaj, Aleksandra and Gerdes, Anne Marie and Giles, Graham G. and Glasspool, Rosalind and Glendon, Gord and Godwin, Andrew K. and Goodman, Marc T. and Gore, Martin and Greene, Mark H. and Grip, Mervi and Gronwald, Jacek and Gschwantler Kaulich, Daphne and Guénel, Pascal and Guzman, Starr R. and Haeberle, Lothar and Haiman, Christopher A. and Hall, Per and Halverson, Sandra L. and Hamann, Ute and Hansen, Thomas V O and Harter, Philipp and Hartikainen, Jaana M. and Healey, Sue and Hein, Alexander and Heitz, Florian and Henderson, Brian E. and Herzog, Josef and T Hildebrandt, Michelle A. and Høgdall, Claus K. and Høgdall, Estrid and Hogervorst, Frans B L and Hopper, John L. and Humphreys, Keith and Huzarski, Tomasz and Imyanitov, Evgeny N. and Isaacs, Claudine and Jakubowska, Anna and Janavicius, Ramunas and Jaworska, Katarzyna and Jensen, Allan and Jensen, Uffe Birk and Johnson, Nichola and Jukkola-Vuorinen, Arja and Kabisch, Maria and Karlan, Beth Y. and Kataja, Vesa and Kauff, Noah 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 Konstantopoulou, Irene and Kosma, Veli Matti and Krakstad, Camilla and Kristensen, Vessela and Kuchenbaecker, Karoline B. and Kupryjanczyk, Jolanta and Laitman, Yael and Lambrechts, Diether and Lambrechts, Sandrina and Larson, Melissa C. and Lasa, Adriana and Laurent-Puig, Pierre and Lazaro, Conxi and Le, Nhu D. and Le Marchand, Loic and Leminen, Arto and Lester, Jenny and Levine, Douglas A. and Li, Jingmei and Liang, Dong and Lindblom, Annika and Lindor, Noralane and Lissowska, Jolanta and Long, Jirong and Lu, Karen H. and Lubinski, Jan and Lundvall, Lene and Lurie, Galina and Mai, Phuong L. and Mannermaa, Arto and Margolin, Sara and Mariette, Frederique and Marme, Frederik and Martens, John W M and Massuger, Leon F A G and Maugard, Christine and Mazoyer, Sylvie and McGuffog, Lesley and McGuire, Valerie and McLean, Catriona and McNeish, Iain and Meindl, Alfons and Menegaux, Florence and Menéndez, Primitiva and Menkiszak, Janusz and Menon, Usha and Mensenkamp, Arjen R. and Miller, Nicola and Milne, Roger L. and Modugno, Francesmary and Montagna, Marco and Moysich, Kirsten B. and Müller, Heiko 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 Nevanlinna, Heli and Neven, Patrick and Nielsen, Finn C. and Nielsen, Sune F. and Nordestgaard, Børge G. and Nussbaum, Robert L. and Odunsi, Kunle and Offit, Kenneth and Olah, Edith and Olopade, Olufunmilayo I. and Olson, Janet E. and Olson, Sara H. and Oosterwijk, Jan C. and Orlow, Irene and Orr, Nick and Orsulic, Sandra and Osorio, Ana and Ottini, Laura and Paul, James and Pearce, Celeste L. and Pedersen, Inge Sokilde and Peissel, Bernard and Pejovic, Tanja and Pelttari, Liisa M. and Perkins, Jo and Permuth-Wey, Jenny and Peterlongo, Paolo and Peto, Julian and Phelan, Catherine M. and Phillips, Kelly Anne and Piedmonte, Marion and Pike, Malcolm C. and Platte, Radka and Plisiecka-Halasa, Joanna and Poole, Elizabeth M. and Poppe, Bruce and Pylkäs, Katri and Radice, Paolo and Ramus, Susan J. and Rebbeck, Timothy R. and Reed, Malcolm W R and Rennert, Gad and Risch, Harvey A. and Robson, Mark and Rodriguez, Gustavo C. and Romero, Atocha and Rossing, Mary Anne and Rothstein, Joseph H. and Rudolph, Anja and Runnebaum, Ingo and Salani, Ritu and Salvesen, Helga B. and Sawyer, Elinor J. and Schildkraut, Joellen M. and Schmidt, Marjanka K. and Schmutzler, Rita K. and Schneeweiss, Andreas and Schoemaker, Minouk J. and Schrauder, Michael G. and Schumacher, Fredrick and Schwaab, Ira and Scuvera, Giulietta and Sellers, Thomas A. and Severi, Gianluca and Seynaeve, Caroline M. and Shah, Mitul and Shrubsole, Martha and Siddiqui, Nadeem and Sieh, Weiva and Simard, Jacques and Singer, Christian F. and Sinilnikova, Olga M. and Smeets, Dominiek and Sohn, Christof and Soller, Maria and Song, Honglin and Soucy, Penny and Southey, Melissa C. and Stegmaier, Christa and Stoppa-Lyonnet, Dominique and Sucheston, Lara and Swerdlow, Anthony and Tangen, Ingvild L. and Tea, Muy Kheng and Teixeira, Manuel R. and Terry, Kathryn L. and Terry, Mary Beth and Thomassen, Mads and Thompson, Pamela J. and Tihomirova, Laima and Tischkowitz, Marc and Toland, Amanda Ewart and Tollenaar, Rob A E M and Tomlinson, Ian and Torres, Diana and Truong, Thérèse and Tsimiklis, Helen and Tung, Nadine 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 Vergote, Ignace and Verhoef, Senno and Vierkant, Robert A. and Vijai, Joseph and Vitonis, Allison F. and Von Wachenfeldt, Anna and Walsh, Christine and Wang, Qin and Wang-Gohrke, Shan and Wappenschmidt, Barbara and Weischer, Maren and Weitzel, Jeffrey N. and Weltens, Caroline and Wentzensen, Nicolas and Whittemore, Alice S. and Wilkens, Lynne R. and Winqvist, Robert and Wu, Anna H. and Wu, Xifeng and Yang, Hannah P. and Zaffaroni, Daniela and Pilar Zamora, M. and Zheng, Wei and Ziogas, Argyrios and Chenevix-Trench, Georgia 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, },
  issn         = {0090-8258},
  keyword      = {Breast cancer,Clinical outcome,Genetic association,KRAS variant,Ovarian cancer},
  language     = {eng},
  month        = {05},
  number       = {2},
  pages        = {386--401},
  publisher    = {ARRAY(0x9cc0eb0)},
  series       = {Gynecologic Oncology},
  title        = {No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer},
  url          = {http://dx.doi.org/10.1016/j.ygyno.2015.04.034},
  volume       = {141},
  year         = {2016},
}