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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.
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, Null;Embrace, Null;GENICA Network, Null;Hebon, Null;SWE BRCA, Null
2016-01-01
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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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/818059
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.