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


Authors: Ovarian Cancer Association Consortium; Breast Cancer Association Consortium; Hollestelle, A.; Van Der Baan, F. H.; Berchuck, A.; Johnatty, S. E.; Aben, K. K.; 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.; Consortium of Modifiers of BRCA1 and BRCA2; Baglietto, L.; Balleine, R.; Bandera, E. V.; Barrowdale, D.; Bean, Y. T.; Beckmann, L.; Beckmann, M. W.; Benitez, J.; Berger, A.; Berger, R.; Beuselinck, B.; Bisogna, M.; Bjorge, L.; Blomqvist, C.; Bogdanova, N. V.; Bojesen, A.; Bojesen, S. E.; Bolla, M. K.; Bonanni, B.; Brand, J. S.; Brauch, H.; Breast Cancer Family Register; Brenner, H.; Brinton, L.; Brooks-Wilson, A.; Bruinsma, F.; Brunet, J.; Brüning, T.; Budzilowska, A.; Bunker, C. H.; Burwinkel, B.; Butzow, R.; Australian Ovarian Cancer Study Group; Buys, S. S.; Caligo, M. A.; Campbell, I.; Carter, J.; Chang-Claude, J.; Chanock, S. J.; Claes, K. B. M.; Collée, J. M.; Cook, L. S.; Couch, F. J.; Cox, A.; Cramer, D.; Cross, S. S.; Cunningham, J. M.; Cybulski, C.; Czene, K.; Damiola, F.; Dansonka-Mieszkowska, A.; Darabi, H.; De La Hoya, M.; Defazio, A.; Dennis, J.; Devilee, P.; Dicks, E. M.; Diez, O.; Doherty, J. A.; Domchek, S. M.; Dorfling, C. M.; Dörk, T.; Silva, I. D. S.; Du Bois, A.; Dumont, M.; Dunning, A. M.; Duran, M.; Easton, D. F.; Eccles, D.; Edwards, R. P.; Ehrencrona, H.; Ejlertsen, B.; Ekici, A. B.; Ellis, S. D.; EMBRACE; Engel, C.; Eriksson, M.; Fasching, P. A.; Feliubadalo, L.; Figueroa, J.; Flesch-Janys, D.; Fletcher, O.; Fontaine, A.; Fortuzzi, S.; Fostira, F.; Fridley, B. L.; Friebel, T.; Friedman, E.; Friel, G.; Frost, D.; Garber, J.; García-Closas, M.; Gayther, S. A.; GEMO Study Collaborators; GENICA Network; Gentry-Maharaj, A.; Gerdes, A. M.; Giles, G. G.; Glasspool, R.; Glendon, G.; Godwin, A. K.; Goodman, M. T.; Gore, M.; Greene, M. H.; Grip, M.; Gronwald, J.; Gschwantler Kaulich, D.; Guénel, P.; Guzman, S. R.; Haeberle, L.; Haiman, C. A.; Hall, P.; Halverson, S. L.; Hamann, U.; Hansen, T. V. O.; Harter, P.; Hartikainen, J. M.; Healey, S.; HEBON; Hein, A.; Heitz, F.; Henderson, B. E.; Herzog, J.; T Hildebrandt, M. A.; Høgdall, C. K.; Høgdall, E.; Hogervorst, F. B. L.; Hopper, J. L.; Humphreys, K.; Huzarski, T.; Imyanitov, E. N.; Isaacs, C.; Jakubowska, A.; Janavicius, R.; Jaworska, K.; Jensen, A.; Jensen, U. B.; Johnson, N.; Jukkola-Vuorinen, A.; Kabisch, M.; Karlan, B. Y.; Kataja, V.; Kauff, N.; KConFab Investigators; Kelemen, L. E.; Kerin, M. J.; Kiemeney, L. A.; Kjaer, S. K.; Knight, J. A.; Knol-Bout, J. P.; Konstantopoulou, I.; Kosma, V. M.; Krakstad, C.; Kristensen, V.; Kuchenbaecker, K. B.; Kupryjanczyk, J.; Laitman, Y.; Lambrechts, D.; Lambrechts, S.; Larson, M. C.; Lasa, A.; Laurent-Puig, P.; Lazaro, C.; Le, N. D.; Le Marchand, L.; Leminen, A.; Lester, J.; Levine, D. A.; Li, J.; Liang, D.; Lindblom, A.; Lindor, N.; Lissowska, J.; Long, J.; Lu, K. H.; Lubinski, J.; Lundvall, L.; Lurie, G.; Mai, P. L.; Mannermaa, A.; Margolin, S.; Mariette, F.; Marme, F.; Martens, J. W. M.; Massuger, L. F. A. G.; Maugard, C.; Mazoyer, S.; McGuffog, L.; McGuire, V.; McLean, C.; McNeish, I.; Meindl, A.; Menegaux, F.; Menéndez, P.; Menkiszak, J.; Menon, U.; Mensenkamp, A. R.; Miller, N.; Milne, R. L.; Modugno, F.; Montagna, M.; Moysich, K. B.; Müller, H.; Mulligan, A. M.; Muranen, T. A.; Narod, S. A.; Nathanson, K. L.; Ness, R. B.; Neuhausen, S. L.; Nevanlinna, H.; Neven, P.; Nielsen, F. C.; Nielsen, S. F.; Nordestgaard, Bø G.; Nussbaum, R. L.; Odunsi, K.; Offit, K.; Olah, E.; Olopade, O. I.; Olson, J. E.; Olson, S. H.; Oosterwijk, J. C.; Orlow, I.; Orr, N.; Orsulic, S.; Osorio, A.; Ottini, L.; Paul, J.; Pearce, C. L.; Pedersen, I. S.; Peissel, B.; Pejovic, T.; Pelttari, L. M.; Perkins, J.; Permuth-Wey, J.; Peterlongo, P.; Peto, J.; Phelan, C. M.; Phillips, K. A.; Piedmonte, M.; Pike, M. C.; Platte, R.; Plisiecka-Halasa, J.; Poole, E. M.; Poppe, B.; Pylkäs, K.; Radice, P.; Ramus, S. J.; Rebbeck, T. R.; Reed, M. W. R.; Rennert, G.; Risch, H. A.; Robson, M.; Rodriguez, G. C.; Romero, A.; Rossing, M. A.; Rothstein, J. H.; Rudolph, A.; Runnebaum, I.; Salani, R.; Salvesen, H. B.; Sawyer, E. J.; Schildkraut, J. M.; Schmidt, M. K.; Schmutzler, R. K.; Schneeweiss, A.; Schoemaker, M. J.; Schrauder, M. G.; Schumacher, F.; Schwaab, I.; Scuvera, G.; Sellers, T. A.; Severi, G.; Seynaeve, C. M.; Shah, M.; Shrubsole, M.; Siddiqui, N.; Sieh, W.; Simard, J.; Singer, C. F.; Sinilnikova, O. M.; Smeets, D.; Sohn, C.; Soller, M.; Song, H.; Soucy, P.; Southey, M. C.; Stegmaier, C.; Stoppa-Lyonnet, D.; Sucheston, L.; Swerdlow, A.; Tangen, I. L.; Tea, M. K.; Teixeira, M. R.; Terry, K. L.; Terry, M. B.; Thomassen, M.; Thompson, P. J.; Tihomirova, L.; Tischkowitz, M.; Toland, A. E.; Tollenaar, R. A. E. M.; Tomlinson, I.; Torres, D.; Truong, T.; Tsimiklis, H.; Tung, N.; Tworoger, S. S.; Tyrer, J. P.; Vachon, C. M.; Van 't Veer, L. J.; Van Altena, A. M.; Van Asperen, C. J.; Van Den Berg, D.; Van Den Ouweland, A. M. W.; Van Doorn, H. C.; Van Nieuwenhuysen, E.; Van Rensburg, E. J.; Vergote, I.; Verhoef, S.; Vierkant, R. A.; Vijai, J.; Vitonis, A. F.; Von Wachenfeldt, A.; Walsh, C.; Wang, Q.; Wang-Gohrke, S.; Wappenschmidt, B.; Weischer, M.; Weitzel, J. N.; Weltens, C.; Wentzensen, N.; Whittemore, A. S.; Wilkens, L. R.; Winqvist, R.; Wu, A. H.; Wu, X.; Yang, H. P.; Zaffaroni, D.; Pilar Zamora, M.; Zheng, W.; Ziogas, A.; Chenevix-Trench, G.; Pharoah, P. D. P.; Rookus, M. A.; Hooning, M. J.; Goode, E. L.
Article 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. © 2015 Elsevier Inc. All rights reserved.
Keywords: ovarian cancer; breast cancer; genetic association; clinical outcome; kras variant
Journal Title: Gynecologic Oncology
Volume: 141
Issue: 2
ISSN: 0090-8258
Publisher: Elsevier Inc.  
Date Published: 2016-05-01
Start Page: 386
End Page: 401
Language: English
DOI: 10.1016/j.ygyno.2015.04.034
PROVIDER: scopus
PMCID: PMC4630206
PUBMED: 25940428
DOI/URL:
Notes: Review -- Export Date: 2 June 2016 -- Source: Scopus
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  1. Malcolm Pike
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  2. Kenneth Offit
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  3. Sara H Olson
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  4. Mark E Robson
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  5. Noah Kauff
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  6. Douglas A Levine
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  7. Irene Orlow
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