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

  • Author(s): Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2
  • 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
  • Australian Ovarian Cancer Study Group
  • 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
  • Breast Cancer Family Register
  • 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 BM
  • 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
  • EMBRACE
  • 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
  • GEMO Study Collaborators
  • GENICA Network
  • 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 VO
  • Harter, Philipp
  • Hartikainen, Jaana M
  • Healey, Sue
  • HEBON
  • Hein, Alexander
  • Heitz, Florian
  • Henderson, Brian E
  • Herzog, Josef
  • T Hildebrandt, Michelle A
  • Høgdall, Claus K
  • Høgdall, Estrid
  • Hogervorst, Frans BL
  • 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
  • KConFab Investigators
  • 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 WM
  • Massuger, Leon FAG
  • 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 WR
  • 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
  • SWE-BRCA
  • 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 AEM
  • 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, CJ
  • van den Berg, David
  • van den Ouweland, Ans MW
  • 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 DP
  • Rookus, Matti A
  • Hooning, Maartje J
  • Goode, Ellen L
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630206/
No data is associated with this publication.
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.

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