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

KConFab Investigators; Ovarian Cancer Association Consortium; Breast Cancer Association Consortium; Consortium of Modifiers of BRCA1 and BRCA2; Australian Ovarian Cancer Study Group; Australian Ovarian Cancer Study Group; Australian Ovarian Cancer Study Group; GEMO Study Collaborators

doi:10.1016/j.ygyno.2015.04.034

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

KConFab Investigators
, Ovarian Cancer Association Consortium
, Breast Cancer Association Consortium
, Consortium of Modifiers of BRCA1 and BRCA2
, Australian Ovarian Cancer Study Group
, Australian Ovarian Cancer Study Group
, Australian Ovarian Cancer Study Group
, GEMO Study Collaborators

Department of Epidemiology and Environmental Health

Peter Maccallum Cancer Centre
Cancer Division
Queensland Institute of Medical Research
Center for Cancer Research
The University of Sydney
UNICANCER Genetic Group
GEMO Study: National Cancer Genetics Network
Erasmus University Rotterdam
Netherlands Cancer Institute
Duke University
Comprehensive Cancer Center the Netherlands
Radboud University Nijmegen
Landspitali University Hospital
University of Iceland
Helsinki University Hospital
IRCCS Istituto Oncologico Veneto - Padova
University of Toronto
University of California at Irvine
Settlement of Lesnoy-2
University of Cambridge
University of Melbourne
German Cancer Research Center
Universitätsklinikum Kiel
University of Texas Health Science Center at Houston
Karolinska Institutet
The Institute of Cancer Research
Cancer Council Victoria
Monash University
The Westmead Institute for Medical Research
Rutgers - The State University of New Jersey, New Brunswick
Oregon Health and Science University
Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen
Friedrich-Alexander University Erlangen-Nürnberg
Spanish National Cancer Research Centre (CNIO)
AvMonforte de Lemos
Medical University of Vienna
Sheba Medical Center at Tel Hashomer
KU Leuven
Memorial Sloan-Kettering Cancer Center
University of Bergen
University of Helsinki
Hannover Medical School
University of Southern Denmark
University of Copenhagen
IRCCS Istituto Europeo di Oncologia - Milano
Robert Bosch Foundation
University of Tübingen
National Institutes of Health
Provincial Health Services Authority
Simon Fraser University
Institute Catala Oncologia
Institute of the Ruhr-Universität Bochum
Maria Sklodowska-Curie Institute of Oncology
University of Pittsburgh
Heidelberg University

Research output: Contribution to journal › Review article › peer-review

12 Scopus citations

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	https://doi.org/10.1016/j.ygyno.2015.04.034
State	Published - May 1 2016

Keywords

Breast cancer
Clinical outcome
Genetic association
KRAS variant
Ovarian cancer

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10.1016/j.ygyno.2015.04.034

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KConFab Investigators, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Consortium of Modifiers of BRCA1 and BRCA2, Australian Ovarian Cancer Study Group, Australian Ovarian Cancer Study Group, Australian Ovarian Cancer Study Group, & GEMO Study Collaborators (2016). No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology, 141(2), 386-401. https://doi.org/10.1016/j.ygyno.2015.04.034

@article{3cfc0a5139ad4c67858678e0da24d715,

title = "No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer",

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.",

keywords = "Breast cancer, Clinical outcome, Genetic association, KRAS variant, Ovarian cancer",

author = "\{KConFab Investigators\} and \{Ovarian Cancer Association Consortium\} and \{Breast Cancer Association Consortium\} and \{Consortium of Modifiers of BRCA1 and BRCA2\} and \{Australian Ovarian Cancer Study Group\} and \{Australian Ovarian Cancer Study Group\} and \{Australian Ovarian Cancer Study Group\} and \{GEMO Study Collaborators\} and Antoinette Hollestelle and \{Van Der Baan\}, \{Frederieke H.\} and Andrew Berchuck and Johnatty, \{Sharon E.\} and Aben, \{Katja K.\} and Agnarsson, \{Bjarni A.\} and Kristiina Aittom{\"a}ki and Elisa Alducci and Andrulis, \{Irene L.\} and Hoda Anton-Culver and Antonenkova, \{Natalia N.\} and Antoniou, \{Antonis C.\} and Carmel Apicella and Volker Arndt and Norbert Arnold and Arun, \{Banu K.\} and Brita Arver and Alan Ashworth and Laura Baglietto and Rosemary Balleine and Bandera, \{Elisa V.\} and Daniel Barrowdale and Bean, \{Yukie T.\} and Lars Beckmann and Beckmann, \{Matthias W.\} and Javier Benitez and Andreas Berger and Raanan Berger and Benoit Beuselinck and Maria Bisogna and Line Bjorge and Carl Blomqvist and Bogdanova, \{Natalia V.\} and Anders Bojesen and Bojesen, \{Stig E.\} and Bolla, \{Manjeet K.\} and Bernardo Bonanni and Brand, \{Judith S.\} and Hiltrud Brauch and Hermann Brenner and Louise Brinton and Angela Brooks-Wilson and Fiona Bruinsma and Joan Brunet and Thomas Br{\"u}ning and Agnieszka Budzilowska and Bunker, \{Clareann H.\} and Barbara Burwinkel and Ralf Butzow and Moysich, \{Kirsten B.\}",

year = "2016",

month = may,

day = "1",

doi = "10.1016/j.ygyno.2015.04.034",

language = "English",

volume = "141",

pages = "386--401",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

number = "2",

}

KConFab Investigators, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Consortium of Modifiers of BRCA1 and BRCA2, Australian Ovarian Cancer Study Group, Australian Ovarian Cancer Study Group, Australian Ovarian Cancer Study Group & GEMO Study Collaborators 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

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 - 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 - Moysich, Kirsten B.

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 -

KConFab Investigators, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Consortium of Modifiers of BRCA1 and BRCA2, Australian Ovarian Cancer Study Group, Australian Ovarian Cancer Study Group et al. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology. 2016 May 1;141(2):386-401. doi: 10.1016/j.ygyno.2015.04.034

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

Abstract

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