Article
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
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Organisations
- (1) Erasmus University Medical Center, grid.5645.2
- (2) Antoni van Leeuwenhoek Hospital, grid.430814.a
- (3) Duke University, grid.26009.3d
- (4) QIMR Berghofer Medical Research Institute, grid.1049.c
- (5) Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands
- (6) Radboud University Nijmegen Medical Centre, grid.10417.33
- (7) National University Hospital of Iceland, grid.410540.4
- (8) University of Iceland, grid.14013.37
- (9) Department of Clinical Genetics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
- (10) Istituto Oncologico Veneto, grid.419546.b
- (11) Ontario Cancer Genetics Network, Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
- (12) University of Toronto, grid.17063.33
- (13) University of California, Irvine, grid.266093.8
- (14) N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
- (15) University of Cambridge, grid.5335.0
- (16) University of Melbourne, grid.1008.9
- (17) German Cancer Research Center, grid.7497.d
- (18) Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, University Kiel, Kiel, Germany
- (19) The University of Texas MD Anderson Cancer Center, grid.240145.6
- (20) Karolinska University Hospital, grid.24381.3c
- (21) Institute of Cancer Research, grid.18886.3f
- (22) Peter MacCallum Cancer Centre, grid.1055.1
- (23) Westmead Institute for Medical Research, grid.452919.2
- (24) Cancer Council Victoria, grid.3263.4
- (25) Monash University, grid.1002.3
- (26) University of Sydney, grid.1013.3
- (27) Rutgers, The State University of New Jersey, grid.430387.b
- (28) Oregon Health & Science University, grid.5288.7
- (29) Institute for Quality and Efficiency in Health Care, grid.414694.a
- (30) University Hospital Erlangen, grid.411668.c
- (31) Spanish National Cancer Research Centre, grid.7719.8
- (32) Centre for Biomedical Network Research on Rare Diseases, grid.452372.5
- (33) Medical University of Vienna, grid.22937.3d
- (34) Sheba Medical Center, grid.413795.d
- (35) Multidisciplinary Breast Center, University Hospital Leuven, University of Leuven, Belgium
- (36) Memorial Sloan Kettering Cancer Center, grid.51462.34
- (37) Haukeland University Hospital, grid.412008.f
- (38) University of Bergen, grid.7914.b
- (39) Department of Oncology, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland
- (40) Hannover Medical School, grid.10423.34
- (41) Vejle Sygehus, grid.417271.6, Southern Denmark Region
- (42) Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
- (43) Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
- (44) European Institute of Oncology, grid.15667.33
- (45) Karolinska Institute, grid.4714.6
- (46) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
- (47) University of Tübingen, grid.10392.39
- (48) Cancer Prevention Institute of California, grid.280669.3
- (49) National Cancer Institute, grid.48336.3a
- (50) Simon Fraser University, grid.61971.38
- (51) BC Cancer Agency, grid.248762.d
- (52) Catalan Institute of Oncology, grid.418701.b
- (53) Ruhr University Bochum, grid.5570.7
- (54) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
- (55) University of Pittsburgh, grid.21925.3d
- (56) Heidelberg University, grid.7700.0
- (57) Helsinki University Central Hospital, grid.15485.3d
- (58) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
- (59) University of Utah, grid.223827.e
- (60) Section of Genetic Oncology, Department of Laboratory Medicine, University Hospital of Pisa, University of Pisa, Pisa, Italy
- (61) Ghent University, grid.5342.0
- (62) University of New Mexico, grid.266832.b
- (63) Mayo Clinic, grid.66875.3a
- (64) University of Sheffield, grid.11835.3e
- (65) Brigham and Women's Hospital, grid.62560.37
- (66) Harvard University, grid.38142.3c
- (67) Pomeranian Medical University, grid.107950.a
- (68) Cancer Center of Lyon, grid.462282.8
- (69) Hospital Clínico San Carlos, grid.411068.a
- (70) Westmead Hospital, grid.413252.3
- (71) Leiden University Medical Center, grid.10419.3d
- (72) Hospital Universitari Vall d'Hebron, grid.411083.f
- (73) Dartmouth College, grid.254880.3
- (74) University of Pennsylvania, grid.25879.31
- (75) University of Pretoria, grid.49697.35
- (76) London School of Hygiene & Tropical Medicine, grid.8991.9
- (77) Helios Dr. Horst Schmidt Kliniken Wiesbaden, grid.491861.3
- (78) Kliniken Essen-Mitte, grid.461714.1
- (79) Laval University, grid.23856.3a
- (80) University of Valladolid, grid.5239.d
- (81) Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK
- (82) Lund University, grid.4514.4
- (83) Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- (84) University of Erlangen-Nuremberg, grid.5330.5
- (85) Leipzig University, grid.9647.c
- (86) University of California, Los Angeles, grid.19006.3e
- (87) University Medical Center Hamburg-Eppendorf, grid.13648.38
- (88) New Mexico Cancer Center, grid.492882.d
- (89) City Of Hope National Medical Center, grid.410425.6
- (90) Cogentech Cancer Genetic Test Laboratory, Milan, Italy
- (91) FIRC Institute of Molecular Oncology, grid.7678.e
- (92) National Centre of Scientific Research Demokritos, grid.6083.d
- (93) University of Kansas Cancer Center, grid.468219.0
- (94) Roswell Park Cancer Institute, grid.240614.5
- (95) Dana-Farber Cancer Institute, grid.65499.37
- (96) University of Southern California, grid.42505.36
- (97) GEMO Study: National Cancer Genetics Network, UNICANCER Genetic Group, France
- (98) Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany
- (99) University of Bonn, grid.10388.32
- (100) University College London, grid.83440.3b
- (101) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- (102) Beatson West of Scotland Cancer Centre, grid.422301.6
- (103) Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
- (104) University of Kansas Medical Center, grid.412016.0
- (105) Cedars-Sinai Medical Center, grid.50956.3f
- (106) Royal Marsden Hospital, grid.424926.f
- (107) Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland
- (108) Centre for research in epidemiology and population health, grid.463845.8
- (109) University of Paris-Sud, grid.5842.b
- (110) Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
- (111) Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- (112) University of Eastern Finland, grid.9668.1
- (113) Kuopio University Hospital, grid.410705.7
- (114) University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany
- (115) Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- (116) University of Copenhagen, grid.5254.6, KU
- (117) Danish Cancer Society, grid.417390.8
- (118) Institute of Oncology NN Petrov, grid.465337.0
- (119) Georgetown University Medical Center, grid.411667.3
- (120) Vilnius University Hospital Santariskiu Klinikos, grid.426597.b
- (121) Medical University of Warsaw, grid.13339.3b
- (122) Aarhus University Hospital, grid.154185.c, Central Denmark Region
- (123) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
- (124) Central Finland Health Care District, grid.460356.2
- (125) Alberta Health Services, grid.413574.0
- (126) University of Calgary, grid.22072.35
- (127) National University of Ireland, Galway, grid.6142.1
- (128) Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
- (129) Oslo University Hospital, grid.55325.34
- (130) University of Oslo, grid.5510.1
- (131) Flanders Institute for Biotechnology, grid.11486.3a
- (132) KU Leuven, grid.5596.f
- (133) Universitair Ziekenhuis Leuven, grid.410569.f
- (134) Sorbonne University, grid.462844.8
- (135) University of Hawaii at Manoa, grid.410445.0
- (136) Texas Southern University, grid.264771.1
- (137) Mayo Clinic, grid.417468.8
- (138) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
- (139) Hôpitaux Universitaires de Strasbourg, grid.412220.7
- (140) Stanford University, grid.168010.e
- (141) The Alfred Hospital, grid.1623.6
- (142) University of Glasgow, grid.8756.c
- (143) Department of Gynecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
- (144) Hospital Monte Naranco, grid.414858.4
- (145) University of Pittsburgh Cancer Institute, grid.478063.e
- (146) University Health Network, grid.231844.8
- (147) The University of Texas Health Science Center at Houston, grid.267308.8
- (148) University of California, San Francisco, grid.266102.1
- (149) National Institute of Oncology, grid.419617.c
- (150) University of Chicago Medical Center, grid.412578.d
- (151) University Medical Center Groningen, grid.4494.d
- (152) Sapienza University of Rome, grid.7841.a
- (153) Aalborg Hospital, grid.27530.33, North Denmark Region
- (154) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
- (155) Moffitt Cancer Center, grid.468198.a
- (156) Department of Medicine, St Vincent's Hospital, The University of Melbourne, Victoria, Australia
- (157) NRG Oncology Statistics and Data Management Center, Buffalo, NY, USA
- (158) Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics, University of Oulu, Oulu University Hospital, Oulu, Finland
- (159) University of Oulu, grid.10858.34
- (160) Clalit National Israeli Cancer Control Center, Haifa, Israel
- (161) Technion – Israel Institute of Technology, grid.6451.6
- (162) Yale University, grid.47100.32
- (163) NorthShore University HealthSystem, grid.240372.0
- (164) Fred Hutchinson Cancer Research Center, grid.270240.3
- (165) University of Washington, grid.34477.33
- (166) Jena University Hospital, grid.275559.9
- (167) The Ohio State University, grid.261331.4
- (168) King's College London, grid.13097.3c
- (169) Duke University Hospital, grid.189509.c
- (170) University Hospital Cologne, grid.411097.a
- (171) Institut für Humangenetik Wiesbaden, Wiesbaden, Germany
- (172) Glasgow Royal Infirmary, grid.411714.6
- (173) Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon, Centre Léon Bérard, Lyon, France
- (174) Skåne University Hospital, grid.411843.b
- (175) Krebsregister Saarland, grid.482902.5
- (176) Institute Curie, grid.418596.7
- (177) Paris Descartes University, grid.10992.33
- (178) Portuguese Oncology Institute, grid.418711.a
- (179) University of Porto, grid.5808.5
- (180) Columbia University, grid.21729.3f
- (181) Odense University Hospital, grid.7143.1, Southern Denmark Region
- (182) Latvian Biomedical Research and Study Centre, grid.419210.f
- (183) McGill University, grid.14709.3b
- (184) University of Oxford, grid.4991.5
- (185) Pontificia Universidad Javeriana, grid.41312.35
- (186) Beth Israel Deaconess Medical Center, grid.239395.7
- (187) University of Ulm, grid.6582.9
- (188) Hospital Universitario La Paz, grid.81821.32
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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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