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Gynecol Oncol. 2016 May;141(2):386-401. doi: 10.1016/j.ygyno.2015.04.034. Epub 2015 May 2.

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

Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2, Hollestelle A1, van der Baan FH2, Berchuck A3, Johnatty SE4, Aben KK5, Agnarsson BA6, Aittomäki K7, Alducci E8, Andrulis IL9, Anton-Culver H10, Antonenkova NN11, Antoniou AC12, Apicella C13, Arndt V14, Arnold N15, Arun BK16, Arver B17, Ashworth A18; Australian Ovarian Cancer Study Group, Baglietto L19, Balleine R20, Bandera EV21, Barrowdale D12, Bean YT22, Beckmann L23, Beckmann MW24, Benitez J25, Berger A26, Berger R27, Beuselinck B28, Bisogna M29, Bjorge L30, Blomqvist C31, Bogdanova NV32, Bojesen A33, Bojesen SE34, Bolla MK12, Bonanni B35, Brand JS36, Brauch H37; Breast Cancer Family Register, Brenner H14, Brinton L38, Brooks-Wilson A39, Bruinsma F19, Brunet J40, Brüning T41, Budzilowska A42, Bunker CH43, Burwinkel B44, Butzow R45, Buys SS46, Caligo MA47, Campbell I48, Carter J49, Chang-Claude J50, Chanock SJ38, Claes KB51, Collée JM52, Cook LS53, Couch FJ54, Cox A55, Cramer D56, Cross SS57, Cunningham JM58, Cybulski C59, Czene K36, Damiola F60, Dansonka-Mieszkowska A42, Darabi H36, de la Hoya M61, deFazio A62, Dennis J12, Devilee P63, Dicks EM64, Diez O65, Doherty JA66, Domchek SM67, Dorfling CM68, Dörk T69, Silva Idos S70, du Bois A71, Dumont M72, Dunning AM64, Duran M73, Easton DF74, Eccles D75, Edwards RP76, Ehrencrona H77, Ejlertsen B78, Ekici AB79, Ellis SD12; EMBRACE, Engel C80, Eriksson M36, Fasching PA81, Feliubadalo L82, Figueroa J38, Flesch-Janys D83, Fletcher O18, Fontaine A84, Fortuzzi S85, Fostira F86, Fridley BL87, Friebel T88, Friedman E89, Friel G90, Frost D12, Garber J91, García-Closas M18, Gayther SA92; GEMO Study Collaborators; GENICA Network, Gentry-Maharaj A93, Gerdes AM94, Giles GG19, Glasspool R95, Glendon G96, Godwin AK97, Goodman MT98, Gore M99, Greene MH100, Grip M101, Gronwald J102, Gschwantler Kaulich D26, Guénel P103, Guzman SR104, Haeberle L24, Haiman CA92, Hall P36, Halverson SL105, Hamann U106, Hansen TV107, Harter P71, Hartikainen JM108, Healey S4; HEBON, Hein A109, Heitz F71, Henderson BE92, Herzog J110, T Hildebrandt MA111, Høgdall CK112, Høgdall E113, Hogervorst FB114, Hopper JL13, Humphreys K36, Huzarski T102, Imyanitov EN115, Isaacs C116, Jakubowska A102, Janavicius R117, Jaworska K118, Jensen A119, Jensen UB120, Johnson N18, Jukkola-Vuorinen A121, Kabisch M106, Karlan BY122, Kataja V123, Kauff N124; KConFab Investigators, Kelemen LE125, Kerin MJ126, Kiemeney LA127, Kjaer SK128, Knight JA129, Knol-Bout JP2, Konstantopoulou I86, Kosma VM108, Krakstad C30, Kristensen V130, Kuchenbaecker KB12, Kupryjanczyk J42, Laitman Y89, Lambrechts D131, Lambrechts S132, Larson MC133, Lasa A134, Laurent-Puig P135, Lazaro C82, Le ND136, Le Marchand L137, Leminen A138, Lester J122, Levine DA29, Li J36, Liang D139, Lindblom A140, Lindor N141, Lissowska J142, Long J105, Lu KH143, Lubinski J102, Lundvall L112, Lurie G137, Mai PL100, Mannermaa A108, Margolin S144, Mariette F85, Marme F145, Martens JW1, Massuger LF146, Maugard C147, Mazoyer S60, McGuffog L12, McGuire V148, McLean C149, McNeish I150, Meindl A151, Menegaux F103, Menéndez P152, Menkiszak J153, Menon U93, Mensenkamp AR154, Miller N126, Milne RL155, Modugno F156, Montagna M8, Moysich KB90, Müller H14, Mulligan AM157, Muranen TA138, Narod SA158, Nathanson KL67, Ness RB159, Neuhausen SL160, Nevanlinna H138, Neven P28, Nielsen FC107, Nielsen SF34, Nordestgaard BG34, Nussbaum RL161, Odunsi K90, Offit K162, Olah E163, Olopade OI164, Olson JE104, Olson SH165, Oosterwijk JC166, Orlow I165, Orr N18, Orsulic S122, Osorio A167, Ottini L168, Paul J95, Pearce CL92, Pedersen IS169, Peissel B170, Pejovic T22, Pelttari LM138, Perkins J12, Permuth-Wey J171, Peterlongo P172, Peto J70, Phelan CM171, Phillips KA173, Piedmonte M174, Pike MC175, Platte R12, Plisiecka-Halasa J42, Poole EM176, Poppe B51, Pylkäs K177, Radice P178, Ramus SJ92, Rebbeck TR179, Reed MW55, Rennert G180, Risch HA181, Robson M162, Rodriguez GC182, Romero A61, Rossing MA183, Rothstein JH148, Rudolph A50, Runnebaum I184, Salani R185, Salvesen HB30, Sawyer EJ186, Schildkraut JM187, Schmidt MK114, Schmutzler RK188, Schneeweiss A145, Schoemaker MJ189, Schrauder MG24, Schumacher F92, Schwaab I190, Scuvera G170, Sellers TA171, Severi G19, Seynaeve CM1, Shah M64, Shrubsole M105, Siddiqui N191, Sieh W148, Simard J72, Singer CF26, Sinilnikova OM192, Smeets D131, Sohn C193, Soller M194, Song H64, Soucy P72, Southey MC195, Stegmaier C196, Stoppa-Lyonnet D197, Sucheston L90; SWE-BRCA, Swerdlow A198, Tangen IL30, Tea MK26, Teixeira MR199, Terry KL56, Terry MB200, Thomassen M201, Thompson PJ98, Tihomirova L202, Tischkowitz M203, Toland AE204, Tollenaar RA205, Tomlinson I206, Torres D207, Truong T103, Tsimiklis H195, Tung N208, Tworoger SS176, Tyrer JP64, Vachon CM104, Van 't Veer LJ114, van Altena AM146, Van Asperen CJ209, van den Berg D92, van den Ouweland AM52, van Doorn HC210, Van Nieuwenhuysen E132, van Rensburg EJ68, Vergote I132, Verhoef S114, Vierkant RA133, Vijai J124, Vitonis AF211, von Wachenfeldt A17, Walsh C122, Wang Q12, Wang-Gohrke S212, Wappenschmidt B188, Weischer M34, Weitzel JN110, Weltens C28, Wentzensen N38, Whittemore AS148, Wilkens LR137, Winqvist R177, Wu AH92, Wu X111, Yang HP38, Zaffaroni D170, Pilar Zamora M213, Zheng W105, Ziogas A214, Chenevix-Trench G4, Pharoah PD64, Rookus MA215, Hooning MJ1, Goode EL104.

Author information

1
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
2
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA. Electronic address: berch001@mc.duke.edu.
4
Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
5
Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands; Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
6
Landspitali University Hospital, Reykjavik, Iceland; University of Iceland, School of Medicine, Reykjavik, Iceland.
7
Department of Clinical Genetics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
8
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
9
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.
10
Department of Epidemiology, University of California Irvine, Irvine, CA, USA.
11
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
12
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
13
Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
14
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
15
Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, University Kiel, Kiel, Germany.
16
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.
17
Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
18
Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
19
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, Australia.
20
Western Sydney and Nepean Blue Mountains Local Health Districts, Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia.
21
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
22
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
23
Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany.
24
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
25
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), Madrid, Spain.
26
Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
27
Sheba Medical Center, Tel Aviv, Israel.
28
Multidisciplinary Breast Center, University Hospital Leuven, University of Leuven, Belgium.
29
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
30
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
31
Department of Oncology, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
32
Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany; Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
33
Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
34
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.
35
Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.
36
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
37
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.
38
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
39
Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
40
Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI-Catalan Institute of Oncology, Girona, Spain.
41
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany.
42
Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
43
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
44
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
45
Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
46
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
47
Section of Genetic Oncology, Department of Laboratory Medicine, University Hospital of Pisa, University of Pisa, Pisa, Italy.
48
Cancer Genetics Laboratory, Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Department of Pathology, University of Melbourne, Melbourne, VIC, Australia.
49
Gynaecological Oncology, The Chris O'Brien Lifehouse and The University of Sydney, Sydney, Australia.
50
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
51
Center for Medical Genetics, Ghent University, Ghent, Belgium.
52
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
53
Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA.
54
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA; Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA.
55
Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, UK.
56
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
57
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
58
Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA.
59
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical Academy, Szczecin, Poland.
60
INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
61
Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain.
62
Center for Cancer Research, University of Sydney at Westmead Millennium Institute, Sydney, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia.
63
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
64
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
65
Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
66
Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
67
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA; Basser Research Centre, Abramson Cancer Center, The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
68
Department of Genetics, University of Pretoria, Pretoria, South Africa.
69
Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
70
Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
71
Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, Wiesbaden, Germany; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
72
Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec, Canada.
73
Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain.
74
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
75
Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
76
Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
77
Department of Clinical Genetics, Lund University, Lund, Sweden.
78
Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
79
Institute of Human Genetics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
80
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
81
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany; David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, CA, USA.
82
Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain.
83
Department of Cancer Epidemiology/Clinical Cancer Registry, Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
84
Clinical Cancer Genetics, City of Hope, Duarte, CA, USA; New Mexico Cancer Center, Albuquerque, NM, USA.
85
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy; Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
86
Molecular Diagnostics Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research Demokritos, Aghia Paraskevi Attikis, Athens, Greece.
87
Kansas IDeA Network of Biomedical Research Excellence Bioinformatics Core, The University of Kansas Cancer Center, Kansas City, KS, USA.
88
University of Pennsylvania, Philadelphia, PA, USA.
89
The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel; Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
90
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
91
Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA.
92
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
93
Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, UCL, London, UK.
94
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
95
Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Glasgow, UK.
96
Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
97
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
98
Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
99
Gynecological Oncology Unit, The Royal Marsden Hospital, London, UK.
100
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
101
Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
102
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
103
INSERM U1018, CESP (Center for Research in Epidemiology and Population Health), Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
104
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
105
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
106
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
107
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
108
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland; School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
109
University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany.
110
Clinical Cancer Genetics, City of Hope, Duarte, CA, USA.
111
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
112
Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
113
Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark; Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
114
Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
115
N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
116
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
117
Vilnius University Hospital Santariskiu Clinics, Hematology, Oncology and Transfusion Medicine Center, Department of Molecular and Regenerative Medicine, State Research Centre Institute for Innovative Medicine, Vilnius, Lithuania.
118
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
119
Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
120
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
121
Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.
122
Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
123
School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, Biocenter Kuopio, Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland; Jyväskylä Central Hospital, Jyväskylä, Finland.
124
Clinical Genetics Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
125
Department of Population Health Research, Alberta Health Services-Cancer Care, Calgary, Alberta, Canada; Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada; Department of Oncology, University of Calgary, Calgary, Alberta, Canada.
126
School of Medicine, National University of Ireland, Galway, Ireland.
127
Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
128
Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
129
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
130
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway; Faculty of Medicine (Faculty Division Ahus), Universitetet i Oslo, Norway.
131
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Belgium; Vesalius Research Center (VRC), VIB, Leuven, Belgium.
132
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium; Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
133
Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
134
Genetic and Molecular Epidemiology Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
135
Université Paris Sorbonne Cité, UMR-S775 Inserm, Paris, France.
136
Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
137
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
138
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
139
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.
140
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
141
Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, USA.
142
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland.
143
Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
144
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
145
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
146
Department of Gynecology, Radboud University Medical Centre, Nijmegen, The Netherlands.
147
Laboratoire de Diagnostic Génétique et Service d'Onco-hématologie, Hopitaux Universitaire de Strasbourg, CHRU Nouvel Hôpital Civil, Strasbourg, France.
148
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.
149
Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
150
Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK.
151
Department of Gynecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
152
Servicio de Anatomía Patológica, Hospital Monte Naranco, Oviedo, Spain.
153
Department of Surgical Gynecology and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.
154
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
155
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.
156
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Women's Cancer Research Program, Magee-Women's Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
157
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
158
Women's College Research Institute, University of Toronto, Toronto, ON, Canada.
159
The University of Texas School of Public Health, Houston, TX, USA.
160
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
161
Department of Medicine and Institute for Human Genetics, University of California, San Francisco, CA, USA.
162
Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
163
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
164
Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL, USA.
165
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
166
University of Groningen, University Medical Center, Department of Genetics, Groningen, The Netherlands.
167
Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain; Genetic and Molecular Epidemiology Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
168
Department of Molecular Medicine, Sapienza University, Rome, Italy.
169
Section of Molecular Diagnostics, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
170
Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Tumori (INT), Milan, Italy.
171
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
172
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy.
173
Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia; Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia; Department of Medicine, St Vincent's Hospital, The University of Melbourne, Victoria, Australia.
174
NRG Oncology Statistics and Data Management Center, Buffalo, NY, USA.
175
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
176
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
177
Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Genetics, University of Oulu, Oulu University Hospital, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland.
178
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori (INT), Milan, Italy.
179
Basser Research Centre, Abramson Cancer Center, The University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
180
Clalit National Israeli Cancer Control Center, Haifa, Israel; Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel.
181
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
182
NorthShore University Health System, University of Chicago, Evanston, IL, USA.
183
Department of Epidemiology, University of Washington, Seattle, WA, USA; Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
184
Department of Gynecology, Jena University Hospital, Jena, Germany.
185
Ohio State University, Columbus, OH, USA.
186
Division of Cancer Studies, NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, London, UK.
187
Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA; Cancer Prevention, Detection and Control Research Program, Duke Cancer Institute, Durham, NC, USA.
188
Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany; Centre for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany.
189
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, UK.
190
Institut für Humangenetik Wiesbaden, Wiesbaden, Germany.
191
Department of Gynecological Oncology, Glasgow Royal Infirmary, Glasgow, UK.
192
INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon, Centre Léon Bérard, Lyon, France.
193
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
194
Department of Clinical Genetics, University and Regional Laboratories, Lund University Hospital, Lund, Sweden.
195
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
196
Saarland Cancer Registry, Saarbrücken, Germany.
197
Institut Curie, Department of Tumour Biology, Paris, France; Institut Curie, INSERM U830, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France.
198
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, UK; Division of Breast Cancer Research, The Institute of Cancer Research, Sutton, Surrey, UK.
199
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal; Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
200
Department of Epidemiology, Columbia University, New York, NY, USA.
201
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
202
Latvian Biomedical Research and Study Centre, Riga, Latvia.
203
Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, Quebec, Canada.
204
Divison of Human Cancer Genetics, Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
205
Department of Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
206
Welcome Trust Centre for Human Genetics, University of Oxford, UK; Oxford Biomedical Research Centre, University of Oxford, UK.
207
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
208
Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
209
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
210
Department of Gynecology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
211
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
212
Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
213
Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
214
Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA.
215
Division of Molecular Pathology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

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.

KEYWORDS:

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

PMID:
25940428
PMCID:
PMC4630206
[Available on 2017-05-01]
DOI:
10.1016/j.ygyno.2015.04.034

Publication type, Grant support

Publication type

Grant support

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