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 language | English |
|---|---|
| Pages (from-to) | 386-401 |
| Number of pages | 16 |
| Journal | Gynecologic Oncology |
| Volume | 141 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - May 1 2016 |
Keywords
- Breast cancer
- Clinical outcome
- Genetic association
- KRAS variant
- Ovarian cancer
ASJC Scopus subject areas
- Obstetrics and Gynaecology
- Oncology
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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.; 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 journal › Article › peer-review
}
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 - Article
AN - SCOPUS:84964863805
VL - 141
SP - 386
EP - 401
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 2
ER -