TY - JOUR
T1 - No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
AU - kConFab Investigators
AU - Ovarian Cancer Association Consortium
AU - Breast Cancer Association Consortium
AU - Consortium of Modifiers of BRCA1 and BRCA2
AU - Australian Ovarian Cancer Study Group
AU - Australian Ovarian Cancer Study Group
AU - Australian Ovarian Cancer Study Group
AU - GEMO Study Collaborators
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 - Torres, Diana
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
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 - https://www.scopus.com/pages/publications/84964863805
U2 - 10.1016/j.ygyno.2015.04.034
DO - 10.1016/j.ygyno.2015.04.034
M3 - Review article
C2 - 25940428
AN - SCOPUS:84964863805
SN - 0090-8258
VL - 141
SP - 386
EP - 401
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -
SDG 3 Good Health and Well-being