Format

Send to

Choose Destination
PLoS One. 2014 Nov 12;9(11):e109973. doi: 10.1371/journal.pone.0109973. eCollection 2014.

MicroRNA related polymorphisms and breast cancer risk.

Khan S1, Greco D2, Michailidou K3, Milne RL4, Muranen TA1, Heikkinen T1, Aaltonen K5, Dennis J3, Bolla MK3, Liu J6, Hall P7, Irwanto A6, Humphreys K7, Li J6, Czene K7, Chang-Claude J8, Hein R9, Rudolph A8, Seibold P8, Flesch-Janys D10, Fletcher O11, Peto J12, dos Santos Silva I12, Johnson N11, Gibson L12, Aitken Z12, Hopper JL13, Tsimiklis H14, Bui M13, Makalic E13, Schmidt DF13, Southey MC14, Apicella C13, Stone J13, Waisfisz Q15, Meijers-Heijboer H15, Adank MA15, van der Luijt RB16, Meindl A17, Schmutzler RK18, Müller-Myhsok B19, Lichtner P20, Turnbull C21, Rahman N21, Chanock SJ22, Hunter DJ23, Cox A24, Cross SS25, Reed MW24, Schmidt MK26, Broeks A26, Van't Veer LJ26, Hogervorst FB26, Fasching PA27, Schrauder MG28, Ekici AB29, Beckmann MW28, Bojesen SE30, Nordestgaard BG30, Nielsen SF30, Flyger H31, Benitez J32, Zamora PM33, Perez JI34, Haiman CA35, Henderson BE35, Schumacher F35, Le Marchand L36, Pharoah PD37, Dunning AM38, Shah M38, Luben R39, Brown J3, Couch FJ40, Wang X40, Vachon C41, Olson JE41, Lambrechts D42, Moisse M42, Paridaens R43, Christiaens MR43, Guénel P44, Truong T44, Laurent-Puig P45, Mulot C45, Marme F46, Burwinkel B47, Schneeweiss A46, Sohn C48, Sawyer EJ49, Tomlinson I50, Kerin MJ51, Miller N51, Andrulis IL52, Knight JA53, Tchatchou S54, Mulligan AM55, Dörk T56, Bogdanova NV57, Antonenkova NN58, Anton-Culver H59, Darabi H7, Eriksson M7, Garcia-Closas M60, Figueroa J22, Lissowska J61, Brinton L22, Devilee P62, Tollenaar RA63, Seynaeve C64, van Asperen CJ65, Kristensen VN66; kConFab Investigators; Australian Ovarian Cancer Study Group, Slager S41, Toland AE67, Ambrosone CB68, Yannoukakos D69, Lindblom A70, Margolin S71, Radice P72, Peterlongo P73, Barile M74, Mariani P75, Hooning MJ76, Martens JW76, Collée JM77, Jager A76, Jakubowska A78, Lubinski J78, Jaworska-Bieniek K79, Durda K78, Giles GG4, McLean C80, Brauch H81, Brüning T82, Ko YD83; GENICA Network, Brenner H84, Dieffenbach AK84, Arndt V85, Stegmaier C86, Swerdlow A87, Ashworth A11, Orr N11, Jones M88, Simard J89, Goldberg MS90, Labrèche F91, Dumont M89, Winqvist R92, Pylkäs K92, Jukkola-Vuorinen A93, Grip M94, Kataja V95, Kosma VM96, Hartikainen JM96, Mannermaa A96, Hamann U97, Chenevix-Trench G98, Blomqvist C99, Aittomäki K100, Easton DF37, Nevanlinna H1.

Collaborators (284)

Brauch H, Lo WY, Justenhoven C, Ko YD, Baisch C, Fischer HP, Hamann U, Brüning T, Pesch B, Rabstein S, Lotz A, Harth V, Aghmesheh M, Amor D, Andrews L, Antill Y, Armitage S, Arnold L, Balleine R, Bankier A, Bastick P, Beesley J, Beilby J, Bennett B, Bennett I, Berry G, Blackburn A, Bogwitz M, Brennan M, Brown M, Buckley M, Burgess M, Burke J, Butow P, Byron K, Callen D, Campbell I, Chauhan D, Chauhan M, Chenevix-Trench G, Christian A, Clarke C, Colley A, Cotton D, Crook A, Cui J, Culling B, Cummings M, Dawson SJ, deFazio A, Delatycki M, Dickson R, Dixon J, Dobrovic A, Dudding T, Edkins T, Edwards S, Eisenbruch M, Farshid G, Fawcett S, Fellows A, Fenton G, Field M, Firgaira F, Flanagan J, Fleming J, Fong P, Forbes J, Fox S, French J, Friedlander M, Gaff C, Gardner M, Gattas M, George P, Giles G, Gill G, Goldblatt J, Greening S, Grist S, Haan E, Hardie K, Harris M, Hart S, Hayward N, Healey S, Heiniger L, Hopper J, Humphrey E, Hunt C, James P, Jenkins M, Jones A, Kefford R, Kidd A, Kiely B, Kirk J, Koehler J, Kollias J, Kovalenko S, Lakhani S, Leaming A, Leary J, Lim J, Lindeman G, Lipton L, Lobb L, Mann G, Marsh D, McLachlan SA, Meiser B, Meldrum C, Milne R, Mitchell G, Newman B, Nightingale S, O'Connell S, O'Loughlin I, Osborne R, Pachter N, Patterson B, Peters L, Phillips K, Price M, Purser L, Reeve T, Reeve J, Richards R, Rickard E, Robinson B, Rudzki B, Saleh M, Salisbury E, Sambrook J, Saunders C, Saunus J, Sayer R, Scott E, Scott R, Scott C, Seshadri R, Sexton A, Sharma R, Shelling A, Simpson P, Southey M, Spurdle A, Suthers G, Sykes P, Taylor D, Taylor J, Thierry B, Thomas S, Thompson E, Thorne H, Townshend S, Trainer A, Tran L, Tucker K, Tyler J, Visvader J, Walker L, Walpole I, Ward R, Waring P, Warner B, Warren G, Williams R, Wilson J, Winship I, Wu K, Young MA, Stuart-Harris R, Kirsten F, Rutovitz J, Clingan P, Glasgow A, Proietto A, Braye S, Otton G, Shannon J, Bonaventura T, Stewart J, Begbie S, Friedlander M, Bell D, Baron-Hay S, Ferrier A, Gard G, Nevell D, Pavlakis N, Valmadre S, Young B, Camaris C, Crouch R, Edwards L, Hacker N, Marsden D, Robertson G, Beale P, Beith J, Carter J, Dalrymple C, Houghton R, Russell P, Anderson L, Links M, Grygiel J, Hill J, Brand A, Byth K, Jaworski R, Harnett P, Sharma R, Wain G, Purdie D, Whiteman D, Ward B, Papadimos D, Crandon A, Cummings M, Horwood K, Obermair A, Perrin L, Wyld D, Nicklin J, Davy M, Oehler MK, Hall C, Dodd T, Healy T, Pittman K, Henderson D, Miller J, Pierdes J, Achan A, Blomfield P, Challis D, McIntosh R, Parker A, Brown B, Rome R, Allen D, Grant P, Hyde S, Laurie R, Robbie M, Healy D, Jobling T, Manolitsas T, McNealage J, Rogers P, Susil B, Sumithran E, Simpson I, Haviv I, Phillips K, Rischin D, Fox S, Johnson D, Lade S, Waring P, Loughrey M, O'Callaghan N, Murray B, Mileshkin L, Allan P, Billson V, Pyman J, Neesham D, Quinn M, Hamilton A, McNally O, Underhill C, Bell R, Ng LF, Blum R, Ganju V, Hammond I, McCartney A, Stewart C, Leung Y, Buck M, Zeps N.

Author information

1
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
2
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Finnish Institute of Occupational Health, Helsinki, Finland.
3
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
4
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
5
Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
6
Human Genetics Division, Genome Institute of Singapore, Singapore, Singapore.
7
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
8
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
9
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; PMV Research Group at the Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
10
Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany.
11
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom.
12
Department of Non-Communicable Disease Epidemiology Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
13
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
14
Department of Pathology, The University of Melbourne, Melbourne, Australia.
15
Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
16
Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
17
Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.
18
Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany; Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
19
Max Planck Institute of Psychiatry, Munich, Germany.
20
Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
21
Section of Cancer Genetics, Institute of Cancer Research, Sutton, United Kingdom.
22
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America.
23
Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
24
CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, United Kingdom.
25
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom.
26
Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
27
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Cancer Erlangen-EMN, Erlangen, Germany; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California Los Angeles, California, United States of America.
28
University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Cancer Erlangen-EMN, Erlangen, Germany.
29
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
30
Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
31
Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
32
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
33
Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain.
34
Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
35
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
36
Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, United States of America.
37
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
38
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
39
Clinical Gerontology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
40
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, United States of America.
41
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, United States of America.
42
Vesalius Research Center (VRC), VIB, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
43
Oncology Department, University Hospital Gasthuisberg, Leuven, Belgium.
44
Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France.
45
Université Paris Sorbonne Cité, UMR-S775 Inserm, Paris, France.
46
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
47
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
48
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
49
Research Oncology, Division of Cancer Studies, King's College London, Guy's Hospital, London, United Kingdom.
50
Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
51
Clinical Science Institute, University Hospital Galway, Galway, Ireland.
52
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
53
Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
54
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
55
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Laboratory Medicine, and the Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
56
Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
57
Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
58
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
59
Department of Epidemiology, University of California Irvine, Irvine, California, United States of America.
60
Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom; Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, United Kingdom.
61
Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
62
Department of Human Genetics & Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
63
Department of Surgical Oncology, Leiden University Medical Center, Leiden, Netherlands.
64
Family Cancer Clinic, Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, Netherlands.
65
Department of Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands.
66
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Biology (EpiGen), University of Oslo, Oslo, Norway; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
67
Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
68
Roswell Park Cancer Institute, Buffalo, New York, United States of America.
69
Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Aghia Paraskevi Attikis, Athens, Greece.
70
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
71
Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden.
72
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.
73
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
74
Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy.
75
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy; Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
76
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
77
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
78
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
79
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
80
Anatomical Pathology, The Alfred Hospital, Melbourne, Australia.
81
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tübingen, Tübingen, Germany.
82
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Bochum, Germany.
83
Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
84
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
85
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
86
Saarland Cancer Registry, Saarbrücken, Germany.
87
Division of Genetics and Epidemiology and Division of Breast Cancer Research, The Institute of Cancer Research, Sutton, Surrey, United Kingdom.
88
Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom.
89
Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec, Canada.
90
Department of Medicine, McGill University, Montreal, Canada; Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada.
91
Départements de Santé Environnementale et Santé au Travail et de Médecine Sociale et Préventive, Université de Montréal, Montreal, Quebec, Canada.
92
Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, NordLab Oulu/Oulu University Hospital, Oulu, Finland.
93
Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland.
94
Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.
95
School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland; Cancer Center, Kuopio University Hospital, Kuopio, Finland.
96
School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
97
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
98
Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
99
Department of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
100
Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Abstract

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

PMID:
25390939
PMCID:
PMC4229095
DOI:
10.1371/journal.pone.0109973
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center