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Sci Rep. 2016 Nov 15;6:36874. doi: 10.1038/srep36874.

rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk.

Author information

1
Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
2
Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.
3
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
4
Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
5
Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
6
Department of Molecular Genetics, University of Toronto, Toronto, Canada.
7
Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.
8
Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
9
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
10
University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
11
Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.
12
Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain.
13
Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
14
Vesalius Research Center, VIB, Leuven, Belgium.
15
Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
16
Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
17
Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
18
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
19
Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
20
Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
21
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
22
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
23
University of Tübingen, Tübingen, Germany.
24
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
25
International Agency for Research on Cancer, Lyon, France.
26
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
27
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
28
Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
29
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
30
Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.
31
Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
32
Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
33
Singapore Eye Research Institute and Singapore National Eye Center, Singapore, Singapore.
34
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.
35
Duke-NUS Graduate Medical School, Singapore, Singapore.
36
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
37
Cancer Research Institute, Seoul National University, Seoul, Korea.
38
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
39
Academic Unit of Molecular Oncology, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
40
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
41
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
42
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
43
David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA.
44
Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK.
45
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
46
Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
47
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
48
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia.
49
Department of Medicine, McGill University, Montreal, Canada.
50
Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Canada.
51
Cancer &Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France.
52
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
53
Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
54
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
55
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
56
Department of Surgery, National University Health System, Singapore, Singapore.
57
Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
58
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
59
Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
60
Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
61
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
62
Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.
63
Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
64
Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
65
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
66
Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway.
67
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
68
Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.
69
Institute of Population Health, University of Manchester, Manchester, UK.
70
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
71
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
72
Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
73
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
74
Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain.
75
Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
76
Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.
77
Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.
78
Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy.
79
National Cancer Institute, Bangkok, Thailand.
80
Research Oncology, Guy's Hospital, King's College London, London, UK.
81
Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands.
82
National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
83
School of Public Health, China Medical University, Taichung, Taiwan.
84
Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
85
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
86
Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.
87
Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia.
88
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
89
Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
90
Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
91
McGill University and Génome Québec Innovation Centre, Montréal, Canada.
92
Research and Technology Assessment Department, National Cancer Institute, Thailand.
93
Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
94
Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia.
95
Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research "Demokritos", Athens, Greece.
96
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
97
Cancer Genomics Netherlands, Utrecht, The Netherlands.

Abstract

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.

PMID:
27845421
PMCID:
PMC5109293
DOI:
10.1038/srep36874
[Indexed for MEDLINE]
Free PMC Article

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