Article open access publication

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

Gynecologic Oncology, Elsevier, ISSN 1095-6859

Volume 141, 2, 2016

DOI:10.1016/j.ygyno.2015.04.034, Dimensions: pub.1016197888, PMC: PMC4630206, PMID: 25940428,

Authors

Aben, Katja K H (5) (6)
Andrulis, Irene L. (11) (12)
Baglietto, Laura (16) (24) (25)
Benitez, Javier (30) (31) (32)
Bjorge, Line (37) (38)
Bojesen, Stig E. (42) (43)
Brauch, Hiltrud (17) (46) (47)
Bruinsma, Fiona (16) (24) (25)
Burwinkel, Barbara (17) (56)
Butzow, Ralf (57) (58)
Campbell, Ian (16) (22)
Cramer, Daniel (65) (66)
deFazio, Anna (23) (70)
du Bois, Andreas (77) (78)
EMBRACE (15)
Fasching, Peter A. (30) (86)
Fontaine, Annette (88) (89)
Fortuzzi, Stefano (90) (91)
Network, GENICA (17) (46) (47) (53) (87) (98) (99)
Giles, Graham G (16) (24) (25)
Gore, Martin (106)
Grip, Mervi (107)
Guénel, Pascal (108) (109)
Hall, Per (45)
Harter, Philipp (77) (78)
Hartikainen, Jaana M (112) (113)
HEBON (2)
Heitz, Florian (77) (78)
Høgdall, Estrid (116) (117)
Jaworska, Katarzyna (67) (121)
Kataja, Vesa (112) (124)
Kelemen, Linda E (125) (126)
Kjaer, Susanne K. (115) (117)
Knight, Julia A. (12) (128)
Kosma, Veli-Matti (112) (113)
Krakstad, Camilla (37) (38)
Kristensen, Vessela (129) (130)
Lambrechts, Diether (131) (132)
Le, Nhu D. (51)
Liang, Dong (136)
L, Phuong (49)
Mannermaa, Arto (112) (113)
Marme, Frederik (56) (138)
Menegaux, Florence (108) (109)
Menon, Usha (100)
Milne, Roger L. (16) (24)
Nielsen, Sune F. (42) (43)
Olah, Edith (149)
Orr, Nick (21)
Osorio, Ana (31) (32)
Paul, James (102)
Phillips, Kelly-Anne (16) (22) (156)
Pike, Malcolm C (36) (96)
Poole, Elizabeth M (65) (66)
Pylkäs, Katri (158) (159)
Rennert, Gad (160) (161)
Rossing, Mary Anne (164) (165)
Salani, Ritu (167)
Salvesen, Helga B. (37) (38)
Schwaab, Ira (171)
Severi, Gianluca (16) (24) (25)
Sieh, Weiva (140)
Sinilnikova, Olga M (68) (173)
Smeets, Dominiek (131) (132)
SWE-BRCA (82)
Tangen, Ingvild L. (37) (38)
Teixeira, Manuel R. (178) (179)
Terry, Kathryn L (65) (66)
Torres, Diana (17) (185)
Truong, Thérèse (108) (109)
Tung, Nadine (186)
Vitonis, Allison F (65) (66)
Wang, Qin (15)
Weischer, Maren (42) (43)
Winqvist, Robert (158) (159)
Wu, Anna H (96)
Wu, Xifeng (19)
Zheng, Wei (110)

* Corresponding author

Affiliations

Organisations

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  2. (2) Antoni van Leeuwenhoek Hospital, grid.430814.a
  3. (3) Duke University, grid.26009.3d
  4. (4) QIMR Berghofer Medical Research Institute, grid.1049.c
  5. (5) Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands
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  8. (8) University of Iceland, grid.14013.37
  9. (9) Department of Clinical Genetics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  10. (10) Istituto Oncologico Veneto, grid.419546.b
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  13. (13) University of California, Irvine, grid.266093.8
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  16. (16) University of Melbourne, grid.1008.9
  17. (17) German Cancer Research Center, grid.7497.d
  18. (18) Department of Gynecology and Obstetrics, University Hospital of Schleswig-Holstein, University Kiel, Kiel, Germany
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  35. (35) Multidisciplinary Breast Center, University Hospital Leuven, University of Leuven, Belgium
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  41. (41) Vejle Sygehus, grid.417271.6, Southern Denmark Region
  42. (42) Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
  43. (43) Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
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  46. (46) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, grid.502798.1
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  58. (58) Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
  59. (59) University of Utah, grid.223827.e
  60. (60) Section of Genetic Oncology, Department of Laboratory Medicine, University Hospital of Pisa, University of Pisa, Pisa, Italy
  61. (61) Ghent University, grid.5342.0
  62. (62) University of New Mexico, grid.266832.b
  63. (63) Mayo Clinic, grid.66875.3a
  64. (64) University of Sheffield, grid.11835.3e
  65. (65) Brigham and Women's Hospital, grid.62560.37
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  67. (67) Pomeranian Medical University, grid.107950.a
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  74. (74) University of Pennsylvania, grid.25879.31
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  80. (80) University of Valladolid, grid.5239.d
  81. (81) Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK
  82. (82) Lund University, grid.4514.4
  83. (83) Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  84. (84) University of Erlangen-Nuremberg, grid.5330.5
  85. (85) Leipzig University, grid.9647.c
  86. (86) University of California, Los Angeles, grid.19006.3e
  87. (87) University Medical Center Hamburg-Eppendorf, grid.13648.38
  88. (88) New Mexico Cancer Center, grid.492882.d
  89. (89) City Of Hope National Medical Center, grid.410425.6
  90. (90) Cogentech Cancer Genetic Test Laboratory, Milan, Italy
  91. (91) FIRC Institute of Molecular Oncology, grid.7678.e
  92. (92) National Centre of Scientific Research Demokritos, grid.6083.d
  93. (93) University of Kansas Cancer Center, grid.468219.0
  94. (94) Roswell Park Cancer Institute, grid.240614.5
  95. (95) Dana-Farber Cancer Institute, grid.65499.37
  96. (96) University of Southern California, grid.42505.36
  97. (97) GEMO Study: National Cancer Genetics Network, UNICANCER Genetic Group, France
  98. (98) Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany
  99. (99) University of Bonn, grid.10388.32
  100. (100) University College London, grid.83440.3b
  101. (101) Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  102. (102) Beatson West of Scotland Cancer Centre, grid.422301.6
  103. (103) Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada
  104. (104) University of Kansas Medical Center, grid.412016.0
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  115. (115) Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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  117. (117) Danish Cancer Society, grid.417390.8
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  122. (122) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  123. (123) Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
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  135. (135) University of Hawaii at Manoa, grid.410445.0
  136. (136) Texas Southern University, grid.264771.1
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  138. (138) National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany
  139. (139) Hôpitaux Universitaires de Strasbourg, grid.412220.7
  140. (140) Stanford University, grid.168010.e
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  142. (142) University of Glasgow, grid.8756.c
  143. (143) Department of Gynecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
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  145. (145) University of Pittsburgh Cancer Institute, grid.478063.e
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  150. (150) University of Chicago Medical Center, grid.412578.d
  151. (151) University Medical Center Groningen, grid.4494.d
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Description

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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2015; 2016: Realized

Research area: Medicine

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2015; 2016: Level 2

Research area: Medicine

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Times Cited: 14

Field Citation Ratio (FCR): 3.62

Relative Citation ratio (RCR): 0.67

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