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 Antonenkova, Antonis C Antoniou, Carmel Apicella, Volker Arndt, Norbert Arnold, Banu K. Arun, Brita Arver, Alan Ashworth, Laura Baglietto, Rosemary BalleineAngela Cox, Graham G. Giles, John L. Hopper, Catriona McLean, Gianluca Severi, Melissa C. Southey, 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 journalReview ArticleResearchpeer-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
DOIs
Publication statusPublished - 1 May 2016

Keywords

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

Cite this

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., Antoniou, A. C., Apicella, C., Arndt, V., Arnold, N., Arun, B. K., Arver, B., Ashworth, A., Baglietto, L., ... 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