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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 Group19, Baglietto L20, Balleine R21, Bandera EV22, Barrowdale D12, Bean YT23, Beckmann L24, Beckmann MW25, Benitez J26, Berger A27, Berger R28, Beuselinck B29, Bisogna M30, Bjorge L31, Blomqvist C32, Bogdanova NV33, Bojesen A34, Bojesen SE35, Bolla MK12, Bonanni B36, Brand JS37, Brauch H38; Breast Cancer Family Register39, Brenner H14, Brinton L40, Brooks-Wilson A41, Bruinsma F20, Brunet J42, Brüning T43, Budzilowska A44, Bunker CH45, Burwinkel B46, Butzow R47, Buys SS48, Caligo MA49, Campbell I50, Carter J51, Chang-Claude J52, Chanock SJ40, Claes KBM53, Collée JM54, Cook LS55, Couch FJ56, Cox A57, Cramer D58, Cross SS59, Cunningham JM60, Cybulski C61, Czene K37, Damiola F62, Dansonka-Mieszkowska A44, Darabi H37, de la Hoya M63, deFazio A64, Dennis J12, Devilee P65, Dicks EM66, Diez O67, Doherty JA68, Domchek SM69, Dorfling CM70, Dörk T71, Silva IDS72, du Bois A73, Dumont M74, Dunning AM66, Duran M75, Easton DF76, Eccles D77, Edwards RP78, Ehrencrona H79, Ejlertsen B80, Ekici AB81, Ellis SD12; EMBRACE12, Engel C82, Eriksson M37, Fasching PA83, Feliubadalo L84, Figueroa J40, Flesch-Janys D85, Fletcher O18, Fontaine A86, Fortuzzi S87, Fostira F88, Fridley BL89, Friebel T90, Friedman E91, Friel G92, Frost D12, Garber J93, García-Closas M18, Gayther SA94; GEMO Study Collaborators95; GENICA Network96, Gentry-Maharaj A97, Gerdes AM98, Giles GG20, Glasspool R99, Glendon G100, Godwin AK101, Goodman MT102, Gore M103, Greene MH104, Grip M105, Gronwald J106, Gschwantler Kaulich D27, Guénel P107, Guzman SR108, Haeberle L25, Haiman CA94, Hall P37, Halverson SL109, Hamann U110, Hansen TVO111, Harter P73, Hartikainen JM112, Healey S4; HEBON113, Hein A114, Heitz F73, Henderson BE94, Herzog J115, T Hildebrandt MA116, Høgdall CK117, Høgdall E118, Hogervorst FBL119, Hopper JL13, Humphreys K37, Huzarski T106, Imyanitov EN120, Isaacs C121, Jakubowska A106, Janavicius R122, Jaworska K123, Jensen A124, Jensen UB125, Johnson N18, Jukkola-Vuorinen A126, Kabisch M110, Karlan BY127, Kataja V128, Kauff N129; KConFab Investigators130, Kelemen LE131, Kerin MJ132, Kiemeney LA133, Kjaer SK134, Knight JA135, Knol-Bout JP2, Konstantopoulou I88, Kosma VM112, Krakstad C31, Kristensen V136, Kuchenbaecker KB12, Kupryjanczyk J44, Laitman Y91, Lambrechts D137, Lambrechts S138, Larson MC139, Lasa A140, Laurent-Puig P141, Lazaro C84, Le ND142, Le Marchand L143, Leminen A144, Lester J127, Levine DA30, Li J37, Liang D145, Lindblom A146, Lindor N147, Lissowska J148, Long J109, Lu KH149, Lubinski J106, Lundvall L117, Lurie G143, Mai PL104, Mannermaa A112, Margolin S150, Mariette F87, Marme F151, Martens JWM1, Massuger LFAG152, Maugard C153, Mazoyer S62, McGuffog L12, McGuire V154, McLean C155, McNeish I156, Meindl A157, Menegaux F107, Menéndez P158, Menkiszak J159, Menon U97, Mensenkamp AR160, Miller N132, Milne RL161, Modugno F162, Montagna M8, Moysich KB92, Müller H14, Mulligan AM163, Muranen TA144, Narod SA164, Nathanson KL69, Ness RB165, Neuhausen SL166, Nevanlinna H144, Neven P29, Nielsen FC111, Nielsen SF35, Nordestgaard BG35, Nussbaum RL167, Odunsi K92, Offit K168, Olah E169, Olopade OI170, Olson JE108, Olson SH171, Oosterwijk JC172, Orlow I171, Orr N18, Orsulic S127, Osorio A173, Ottini L174, Paul J99, Pearce CL94, Pedersen IS175, Peissel B176, Pejovic T23, Pelttari LM144, Perkins J12, Permuth-Wey J177, Peterlongo P178, Peto J72, Phelan CM177, Phillips KA179, Piedmonte M180, Pike MC181, Platte R12, Plisiecka-Halasa J44, Poole EM182, Poppe B53, Pylkäs K183, Radice P184, Ramus SJ94, Rebbeck TR185, Reed MWR57, Rennert G186, Risch HA187, Robson M168, Rodriguez GC188, Romero A63, Rossing MA189, Rothstein JH154, Rudolph A52, Runnebaum I190, Salani R191, Salvesen HB31, Sawyer EJ192, Schildkraut JM193, Schmidt MK119, Schmutzler RK194, Schneeweiss A151, Schoemaker MJ195, Schrauder MG25, Schumacher F94, Schwaab I196, Scuvera G176, Sellers TA177, Severi G20, Seynaeve CM1, Shah M66, Shrubsole M109, Siddiqui N197, Sieh W154, Simard J74, Singer CF27, Sinilnikova OM198, Smeets D137, Sohn C199, Soller M200, Song H66, Soucy P74, Southey MC201, Stegmaier C202, Stoppa-Lyonnet D203, Sucheston L92; SWE-BRCA204, Swerdlow A205, Tangen IL31, Tea MK27, Teixeira MR206, Terry KL58, Terry MB207, Thomassen M208, Thompson PJ102, Tihomirova L209, Tischkowitz M210, Toland AE211, Tollenaar RAEM212, Tomlinson I213, Torres D214, Truong T107, Tsimiklis H201, Tung N215, Tworoger SS182, Tyrer JP66, Vachon CM108, Van 't Veer LJ119, van Altena AM152, Van Asperen CJ216, van den Berg D94, van den Ouweland AMW54, van Doorn HC217, Van Nieuwenhuysen E138, van Rensburg EJ70, Vergote I138, Verhoef S119, Vierkant RA139, Vijai J129, Vitonis AF218, von Wachenfeldt A17, Walsh C127, Wang Q12, Wang-Gohrke S219, Wappenschmidt B194, Weischer M35, Weitzel JN115, Weltens C29, Wentzensen N40, Whittemore AS154, Wilkens LR143, Winqvist R183, Wu AH94, Wu X116, Yang HP40, Zaffaroni D176, Pilar Zamora M220, Zheng W109, Ziogas A221, Chenevix-Trench G4, Pharoah PDP66, Rookus MA222, Hooning MJ1, Goode EL108.

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
Cancer Division, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia; Peter MacCallum Cancer Institute, Melbourne, VIC, Australia; Center for Cancer Research, University of Sydney at Westmead Millennium Institute, Sydney, Australia.
20
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.
21
Western Sydney and Nepean Blue Mountains Local Health Districts, Westmead Millennium Institute for Medical Research, University of Sydney, Sydney, Australia.
22
Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
23
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
24
Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, Germany.
25
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
26
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.
27
Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
28
Sheba Medical Center, Tel Aviv, Israel.
29
Multidisciplinary Breast Center, University Hospital Leuven, University of Leuven, Belgium.
30
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
31
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
32
Department of Oncology, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
33
Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany; Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
34
Department of Clinical Genetics, Vejle Hospital, Vejle, Denmark.
35
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.
36
Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.
37
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
38
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.
39
Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA.
40
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
41
Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
42
Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI-Catalan Institute of Oncology, Girona, Spain.
43
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany.
44
Department of Pathology and Laboratory Diagnostics, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
45
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
46
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
47
Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
48
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
49
Section of Genetic Oncology, Department of Laboratory Medicine, University Hospital of Pisa, University of Pisa, Pisa, Italy.
50
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.
51
Gynaecological Oncology, The Chris O'Brien Lifehouse and The University of Sydney, Sydney, Australia.
52
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
53
Center for Medical Genetics, Ghent University, Ghent, Belgium.
54
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
55
Division of Epidemiology and Biostatistics, University of New Mexico, Albuquerque, NM, USA.
56
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.
57
Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, UK.
58
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.
59
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
60
Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN, USA.
61
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical Academy, Szczecin, Poland.
62
INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
63
Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain.
64
Center for Cancer Research, University of Sydney at Westmead Millennium Institute, Sydney, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia.
65
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
66
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
67
Oncogenetics Laboratory, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
68
Section of Biostatistics and Epidemiology, The Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
69
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.
70
Department of Genetics, University of Pretoria, Pretoria, South Africa.
71
Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
72
Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, UK.
73
Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Klinik Wiesbaden, Wiesbaden, Germany; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
74
Centre Hospitalier Universitaire de Québec Research Center, Laval University, Quebec, Canada.
75
Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain.
76
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.
77
Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK.
78
Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
79
Department of Clinical Genetics, Lund University, Lund, Sweden.
80
Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
81
Institute of Human Genetics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
82
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
83
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.
84
Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain.
85
Department of Cancer Epidemiology/Clinical Cancer Registry, Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
86
Clinical Cancer Genetics, City of Hope, Duarte, CA, USA; New Mexico Cancer Center, Albuquerque, NM, USA.
87
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy; Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
88
Molecular Diagnostics Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research Demokritos, Aghia Paraskevi Attikis, Athens, Greece.
89
Kansas IDeA Network of Biomedical Research Excellence Bioinformatics Core, The University of Kansas Cancer Center, Kansas City, KS, USA.
90
University of Pennsylvania, Philadelphia, PA, USA.
91
The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel; Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
92
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
93
Center for Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA, USA.
94
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
95
GEMO Study: National Cancer Genetics Network, UNICANCER Genetic Group, France.
96
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany; Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany; Institute of Pathology, Medical Faculty of the University of Bonn, Bonn, Germany; Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Cancer Research Center (DKFZ), Heidelberg, Germany.
97
Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health, UCL, London, UK.
98
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
99
Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre, Glasgow, UK.
100
Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
101
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
102
Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
103
Gynecological Oncology Unit, The Royal Marsden Hospital, London, UK.
104
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
105
Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
106
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
107
INSERM U1018, CESP (Center for Research in Epidemiology and Population Health), Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
108
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
109
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
110
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
111
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
112
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.
113
The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating Center: Netherlands Cancer Institute, Amsterdam, The Netherlands.
114
University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center, Erlangen, Germany.
115
Clinical Cancer Genetics, City of Hope, Duarte, CA, USA.
116
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
117
Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
118
Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark; Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
119
Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
120
N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
121
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
122
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.
123
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
124
Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
125
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
126
Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.
127
Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
128
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.
129
Clinical Genetics Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
130
kConFab: Kathleen Cuningham Consortium for Research into Familial Breast Cancer - Peter MacCallum Cancer Center, Melbourne, Australia.
131
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.
132
School of Medicine, National University of Ireland, Galway, Ireland.
133
Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
134
Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
135
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.
136
Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway; Faculty of Medicine (Faculty Division Ahus), Universitetet i Oslo, Norway.
137
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Belgium; Vesalius Research Center (VRC), VIB, Leuven, Belgium.
138
Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium; Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
139
Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
140
Genetic and Molecular Epidemiology Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
141
Université Paris Sorbonne Cité, UMR-S775 Inserm, Paris, France.
142
Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
143
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
144
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
145
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.
146
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
147
Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, USA.
148
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland.
149
Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
150
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
151
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
152
Department of Gynecology, Radboud University Medical Centre, Nijmegen, The Netherlands.
153
Laboratoire de Diagnostic Génétique et Service d'Onco-hématologie, Hopitaux Universitaire de Strasbourg, CHRU Nouvel Hôpital Civil, Strasbourg, France.
154
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.
155
Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
156
Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK.
157
Department of Gynecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
158
Servicio de Anatomía Patológica, Hospital Monte Naranco, Oviedo, Spain.
159
Department of Surgical Gynecology and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.
160
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
161
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.
162
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.
163
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
164
Women's College Research Institute, University of Toronto, Toronto, ON, Canada.
165
The University of Texas School of Public Health, Houston, TX, USA.
166
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
167
Department of Medicine and Institute for Human Genetics, University of California, San Francisco, CA, USA.
168
Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
169
Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.
170
Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL, USA.
171
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
172
University of Groningen, University Medical Center, Department of Genetics, Groningen, The Netherlands.
173
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.
174
Department of Molecular Medicine, Sapienza University, Rome, Italy.
175
Section of Molecular Diagnostics, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
176
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.
177
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
178
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), Milan, Italy.
179
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.
180
NRG Oncology Statistics and Data Management Center, Buffalo, NY, USA.
181
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.
182
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.
183
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.
184
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.
185
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.
186
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.
187
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
188
NorthShore University Health System, University of Chicago, Evanston, IL, USA.
189
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.
190
Department of Gynecology, Jena University Hospital, Jena, Germany.
191
Ohio State University, Columbus, OH, USA.
192
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.
193
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.
194
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.
195
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, UK.
196
Institut für Humangenetik Wiesbaden, Wiesbaden, Germany.
197
Department of Gynecological Oncology, Glasgow Royal Infirmary, Glasgow, UK.
198
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.
199
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
200
Department of Clinical Genetics, University and Regional Laboratories, Lund University Hospital, Lund, Sweden.
201
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
202
Saarland Cancer Registry, Saarbrücken, Germany.
203
Institut Curie, Department of Tumour Biology, Paris, France; Institut Curie, INSERM U830, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France.
204
Department of Oncology, Lund University, Lund, Sweden.
205
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.
206
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal; Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.
207
Department of Epidemiology, Columbia University, New York, NY, USA.
208
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
209
Latvian Biomedical Research and Study Centre, Riga, Latvia.
210
Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, Quebec, Canada.
211
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.
212
Department of Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
213
Welcome Trust Centre for Human Genetics, University of Oxford, UK; Oxford Biomedical Research Centre, University of Oxford, UK.
214
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany; Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
215
Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
216
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
217
Department of Gynecology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
218
Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
219
Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
220
Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
221
Department of Epidemiology, Center for Cancer Genetics Research and Prevention, School of Medicine, University of California Irvine, Irvine, CA, USA.
222
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
DOI:
10.1016/j.ygyno.2015.04.034
[Indexed for MEDLINE]
Free PMC Article

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