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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)386-401
Number of pages16
JournalGynecologic Oncology
Volume141
Issue number2
DOIs
StatePublished - May 1 2016

Fingerprint

Ovarian Neoplasms
Breast Neoplasms
Mutation
Survival
Genetic Testing
3' Untranslated Regions
MicroRNAs
Neoplasms
Binding Sites

Keywords

  • Breast cancer
  • Clinical outcome
  • Genetic association
  • KRAS variant
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

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

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. / Ovarian Cancer Association Consortium; Breast Cancer Association Consortium; Consortium of Modifiers of BRCA1 and BRCA2; Australian Ovarian Cancer Study Group; GEMO Study Collaborators; KConFab investigators.

In: Gynecologic Oncology, Vol. 141, No. 2, 01.05.2016, p. 386-401.

Research output: Contribution to journalArticle

Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Consortium of Modifiers of BRCA1 and BRCA2, Australian Ovarian Cancer Study Group, GEMO Study Collaborators & KConFab investigators 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
Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Consortium of Modifiers of BRCA1 and BRCA2, Australian Ovarian Cancer Study Group, GEMO Study Collaborators, KConFab investigators. No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology. 2016 May 1;141(2):386-401. https://doi.org/10.1016/j.ygyno.2015.04.034
Ovarian Cancer Association Consortium ; Breast Cancer Association Consortium ; Consortium of Modifiers of BRCA1 and BRCA2 ; Australian Ovarian Cancer Study Group ; GEMO Study Collaborators ; KConFab investigators. / No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. In: Gynecologic Oncology. 2016 ; Vol. 141, No. 2. pp. 386-401.
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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 = "{Ovarian Cancer Association Consortium} and {Breast Cancer Association Consortium} and {Consortium of Modifiers of BRCA1 and BRCA2} and {Australian Ovarian Cancer Study Group} and {GEMO Study Collaborators} and {KConFab investigators} 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 Couch, {Fergus J} and Cunningham, {Julie M} and Lindor, {Noralane Morey} and Olson, {Janet E} and Vachon, {Celine M} and Goode, {Ellen L}",
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TY - JOUR

T1 - No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

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 - KConFab investigators

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 - Couch, Fergus J

AU - Cunningham, Julie M

AU - Lindor, Noralane Morey

AU - Olson, Janet E

AU - Vachon, Celine M

AU - Goode, Ellen L

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

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