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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.
Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew; Johnatty, Sharon E; Aben, Katja K; Agnarsson, Bjarni A; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Antoniou, Antonis C; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Barrowdale, Daniel; Bean, Yukie T; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Brüning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.
Affiliation
  • Hollestelle A; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
  • van der Baan FH; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Berchuck A; Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. Electronic address: berch001@mc.duke.edu.
  • Johnatty SE; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Aben KK; Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands; Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
  • Agnarsson BA; Landspitali University Hospital, Reykjavik, Iceland; University of Iceland, School of Medicine, Reykjavik, Iceland.
  • Aittomäki K; Department of Clinical Genetics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
  • Alducci E; Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
  • Andrulis IL; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Ontario Cancer Genetics Network, Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
  • Anton-Culver H; Department of Epidemiology, University of California Irvine, Irvine, CA, USA.
  • Antonenkova NN; N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
  • Antoniou AC; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Apicella C; Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
  • Arndt V; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • Arnold N; Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, University Kiel, Kiel, Germany.
  • Arun BK; Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Clinical Cancer Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Arver B; Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
  • Ashworth A; Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
  • Baglietto L; Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC
  • Balleine R; Western Sydney and Nepean Blue Mountains Local Health Districts, Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia.
  • Bandera EV; Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
  • Barrowdale D; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Bean YT; Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
  • Beckmann L; Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany.
  • Beckmann MW; University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
  • Benitez J; Centro Nacional de Genotipación, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany; Biomedical Network on Rare Diseases (CIBERER),
  • Berger A; Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
  • Berger R; Sheba Medical Center, Tel Aviv, Israel.
  • Beuselinck B; Multidisciplinary Breast Center, University Hospital Leuven, University of Leuven, Belgium.
  • Bisogna M; Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
  • Bjorge L; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Blomqvist C; Department of Oncology, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
  • Bogdanova NV; Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany; Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
  • Bojesen A; Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
  • Bojesen SE; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Bolla MK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Bonanni B; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.
  • Brand JS; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Brauch H; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
  • Brinton L; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Brooks-Wilson A; Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
  • Bruinsma F; Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC
  • Brunet J; Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI-Catalan Institute of Oncology, Girona, Spain.
  • Brüning T; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany.
  • Budzilowska A; Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
  • Bunker CH; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
  • Burwinkel B; Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Butzow R; Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
  • Buys SS; Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Gynecol Oncol ; 141(2): 386-401, 2016 05.
Article in En | MEDLINE | ID: mdl-25940428
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Breast Neoplasms / Proto-Oncogene Proteins p21(ras) / Neoplasms, Glandular and Epithelial Type of study: Prognostic_studies Limits: Female / Humans Language: En Journal: Gynecol Oncol Year: 2016 Type: Article Affiliation country: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ovarian Neoplasms / Breast Neoplasms / Proto-Oncogene Proteins p21(ras) / Neoplasms, Glandular and Epithelial Type of study: Prognostic_studies Limits: Female / Humans Language: En Journal: Gynecol Oncol Year: 2016 Type: Article Affiliation country: Netherlands