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

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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 , 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 , Brenner , H , Brinton , L , Brooks-Wilson , A , Bruinsma , F , Brunet , J , Bruning , T , Butzow , R , Leminen , A , Muranen , T A , Nevanlinna , H , Pelttari , L M , Ovarian Canc Assoc Consortium , Breast Canc Assoc Consortium , Consortium Modifiers BRCA1 & BRCA2 , Australian Ovarian Canc Study Grp , Breast Cancer Family Register , EMBRACE , GEMO Study Collaborators , GENICA Network , HEBON , kConFab Investigators & SWE-BRCA 2016 , ' No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer ' , Gynecologic Oncology , vol. 141 , no. 2 , pp. 386-401 . https://doi.org/10.1016/j.ygyno.2015.04.034

Title: No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
Author: 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; Bruning, Thomas; Butzow, Ralf; Leminen, Arto; Muranen, Taru A.; Nevanlinna, Heli; Pelttari, Liisa M.; Ovarian Canc Assoc Consortium; Breast Canc Assoc Consortium; Consortium Modifiers BRCA1 & BRCA2; Australian Ovarian Canc Study Grp; Breast Cancer Family Register; EMBRACE; GEMO Study Collaborators; GENICA Network; HEBON; kConFab Investigators; SWE-BRCA
Contributor organization: Medicum
Kristiina Aittomäki / Principal Investigator
Department of Medical and Clinical Genetics
Clinicum
Department of Oncology
Department of Pathology
Department of Obstetrics and Gynecology
HUS Gynecology and Obstetrics
Date: 2016-05
Language: eng
Number of pages: 16
Belongs to series: Gynecologic Oncology
ISSN: 0090-8258
DOI: https://doi.org/10.1016/j.ygyno.2015.04.034
URI: http://hdl.handle.net/10138/223960
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 = 034, 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. (C) 2015 Elsevier Inc. All rights reserved.
Subject: KRAS variant
Breast cancer
Ovarian cancer
Genetic association
Clinical outcome
GENOME-WIDE ASSOCIATION
MICRORNA-BINDING-SITE
SUSCEPTIBILITY LOCI
RISK
PROSTATE
IDENTIFICATION
POLYMORPHISMS
ENDOMETRIOSIS
WOMEN
3123 Gynaecology and paediatrics
3122 Cancers
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion


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