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

Antoinette Hollestelle, Erasmus MC Cancer Institute
Frederieke H. Van Der Baan, The Netherlands Cancer Institute
Andrew Berchuck, Duke Cancer Institute
Sharon E. Johnatty, QIMR Berghofer Medical Research Institute
Katja K. Aben, Comprehensive Cancer Center the Netherlands
Bjarni A. Agnarsson, Landspitali - The National University Hospital of Iceland
Kristiina Aittomäki, Helsinki University Hospital
Elisa Alducci, Istituto Oncologico Veneto IOV - IRCCS
Irene L. Andrulis, University of Toronto
Hoda Anton-Culver, University of California, Irvine
Natalia N. Antonenkova, Research Institute of Oncology and Medical Radiology of the Ministry of Health of the Byelorussian SSR
Antonis C. Antoniou, University of Cambridge
Carmel Apicella, University of Melbourne
Volker Arndt, German Cancer Research Center
Norbert Arnold, Universitätsklinikum Schleswig-Holstein Campus Kiel
Banu K. Arun, University of Texas Health Science Center at Houston
Brita Arver, Karolinska Universitetssjukhuset
Alan Ashworth, The Institute of Cancer Research
Laura Baglietto, University of Melbourne
Rosemary Balleine, The Westmead Institute for Medical Research
Elisa V. Bandera, Rutgers Robert Wood Johnson Medical School at New Brunswick


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.