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

Research output: Contribution to journalReview articlepeer-review

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
StatePublished - 1 May 2016
Externally publishedYes

Funding

FundersFunder number
Barbara Thomason Ovarian Cancer ResearchSIOP-06-090-06
Cancer Foundation of Western Australia
German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research01 GB 9401
Imperial Experimental Cancer Research CentreC1312/A15589
L & S Milken Foundation
Lon V. Smith FoundationLVS-39420
Nationaal Kankerplan of Belgium
OHSU Foundation
Royal Marsden Hospital
Rudolf-Bartling Foundation
University College Hospital
American Cancer SocietySIOP-06-258-01-COUN, CRTG-00-196-01-CCE
American Cancer Society
National Cancer InstituteR01-CA064277, R01-CA126841, R01-CA016056, R01-CA122443, R01-CA106414, R01-CA063682, R01-CA058598, R01-CA149429, R37-CA070867, N01-CN55424, R01-CA071766, K07-CA143047, R01-095023, R03-CA115195, R01-CA112523, R01-CA080978, R01-CA114343, N01-PC067010, R01-CA049449, R01-CA063678, R01-CA014089, P50-CA105009, R03-CA113148, R01-CA017054, R01-CA061132, K07-CA095666, R01-CA058860, P01-CA087696, P50-CA136393, R01-CA054419, U01-CA069417, R01CA067262, R01-CA050385, N01-PC035137, P30-CA15083, R01-CA076016, U19-CA148112, R01-CA087538, R01-CA092044, R01CA83918, U01-CA071966, K22-CA138563, R01-CA061107
National Cancer Institute
Medical Research and Materiel CommandDAMD17-02-1-0666, DAMD17-98-1-8659, DAMD17-02-1-0669, DAMD17-01-1-0729, W81XWH-07-0449
Medical Research and Materiel Command
Oak foundation
Ovarian Cancer Research FundPPD/RPCI.07
Ovarian Cancer Research Fund
Celma Mastry Ovarian Cancer Foundation
Minnesota Ovarian Cancer Alliance
California Breast Cancer Research Program2II0200, 00-01389V-20170, N01-CN25403
California Breast Cancer Research Program
Roswell Park Alliance Foundation, Roswell Park Cancer Institute
Mayo Foundation for Medical Education and Research
Rutgers Cancer Institute of New Jersey
Kræftens Bekæmpelse94-222-52
Kræftens Bekæmpelse
Helsingin ja Uudenmaan Sairaanhoitopiiri
Wellcome Trust076113
Wellcome Trust
Seventh Framework Programme223175
Seventh Framework Programme
Canadian Institutes of Health Research
National Institute for Health and Care Research
Cancer Research UKC490/A10119, C490/A10124, C536/A6689, C490/A6187, C536/A13086
Cancer Research UK
National Health and Medical Research Council400281, 199600
National Health and Medical Research Council
Cancer Council South Australia
Cancer Council Victoria
Cancer Council NSW
Cancer Council Queensland
Cancer Council Tasmania
Friedrich-Alexander-Universität Erlangen-Nürnberg
Ministerstwo Edukacji i Nauki2 PO5A 068 27, 4 PO5C 028 14
Ministerstwo Edukacji i Nauki
Deutsche Krebshilfe
Universität UlmP.685
Universität Ulm

    Keywords

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

    Fingerprint

    Dive into the research topics of 'No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer'. Together they form a unique fingerprint.

    Cite this