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

Antoinette Hollestelle, Frederieke H van der Baan, Andrew Berchuck, Sharon E Johnatty, Katja K Aben, Bjarni A Agnarsson, Kristiina Aittomäki, Elisa Alducci, Irene L Andrulis, Hoda Anton-Culver, Natalia N Antonenkova, Antonis C Antoniou, Carmel Apicella, Volker Arndt, Norbert Arnold, Banu K Arun, Brita Arver, Alan Ashworth, Laura Baglietto, Rosemary BalleineElisa V Bandera, Daniel Barrowdale, Yukie T Bean, Lars Beckmann, Matthias W Beckmann, Javier Benitez, Andreas Berger, Raanan Berger, Benoit Beuselinck, Maria Bisogna, Line Bjorge, Carl Blomqvist, Natalia V Bogdanova, Anders Bojesen, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Judith S Brand, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Thomas Brüning, Agnieszka Budzilowska, Clareann H Bunker, Barbara Burwinkel, Julie M Cunningham, Robert P Edwards, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2

Research output: Contribution to journalReview article (Academic Journal)peer-review

8 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
Pages (from-to)386-401
Number of pages16
JournalGynecologic Oncology
Volume141
Issue number2
Early online date2 May 2015
DOIs
Publication statusE-pub ahead of print - 2 May 2015

Keywords

  • Breast Neoplasms
  • Female
  • Humans
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms
  • Proto-Oncogene Proteins p21(ras)
  • Journal Article
  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Intramural

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