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

Liu J 1 , Lončar I 1 , Collée JM 2 , Bolla MK 3 , Dennis J 3 , Michailidou K 3 Show all authors , Wang Q 3 , Andrulis IL 4 , Barile M 5 , Beckmann MW 6 , Behrens S 7 , Benitez J 8 , Blomqvist C 9 , Boeckx B 10 , Bogdanova NV 11 , Bojesen SE 12 , Brauch H 13 , Brennan P 14 , Brenner H 15 , Broeks A 16 , Burwinkel B 17 , Chang-Claude J 7 , Chen ST 18 , Chenevix-Trench G 19 , Cheng CY 20 , Choi JY 21 , Couch FJ 22 , Cox A 23 , Cross SS 24 , Cuk K 25 , Czene K 26 , Dörk T 27 , Dos-Santos-Silva I 28 , Fasching PA 6 , Figueroa J 29 , Flyger H 30 , García-Closas M 31 , Giles GG 32 , Glendon G 4 , Goldberg MS 33 , González-Neira A 8 , Guénel P 34 , Haiman CA 35 , Hamann U 36 , Hart SN 37 , Hartman M 38 , Hatse S 39 , Hopper JL 40 , Ito H 41 , Jakubowska A 42 , Kabisch M 36 , Kang D 21 , Kosma VM 43 , Kristensen VN 44 , Le Marchand L 45 , Lee E 35 , Li J 26 , Lophatananon A 46 , Jan Lubinski 42 , Mannermaa A 43 , Matsuo K 47 , Milne RL 32 , NBCS Collaborators , Neuhausen SL 48 , Nevanlinna H 49 , Orr N 50 , Perez JI 51 , Peto J 28 , Putti TC 52 , Pylkäs K 53 , Radice P 54 , Sangrajrang S 55 , Sawyer EJ 56 , Schmidt MK 16 , Schneeweiss A 17 , Shen CY 57 , Shrubsole MJ 58 , Shu XO 58 , Simard J 59 , Southey MC 60 , Swerdlow A 50 , Teo SH 61 , Tessier DC 62 , Thanasitthichai S 63 , Tomlinson I 64 , Torres D 36 , Truong T 34 , Tseng CC 35 , Vachon C 37 , Winqvist R 53 , Wu AH 35 , Yannoukakos D 65 , Zheng W 58 , Hall P 26 , Dunning AM 66 , Easton DF 3 , Hooning MJ 1 , van den Ouweland AM 2 , Martens JW 1 , Hollestelle A 1

Affiliations 

  • 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 Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada
  • 5 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy
  • 6 Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany
  • 7 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 8 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain
  • 9 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 10 Vesalius Research Center, VIB, Leuven, Belgium
  • 11 Department of Radiation Oncology, Hannover Medical School, Hannover, Germany
  • 12 Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 13 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
  • 14 International Agency for Research on Cancer, Lyon, France
  • 15 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 16 Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
  • 17 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany
  • 18 Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
  • 19 Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 20 Singapore Eye Research Institute and Singapore National Eye Center, Singapore, Singapore
  • 21 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
  • 22 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • 23 Academic Unit of Molecular Oncology, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
  • 24 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK
  • 25 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 26 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 27 Gynaecology Research Unit, Hannover Medical School, Hannover, Germany
  • 28 Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
  • 29 Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK
  • 30 Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
  • 31 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
  • 32 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia
  • 33 Department of Medicine, McGill University, Montreal, Canada
  • 34 Cancer &Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France
  • 35 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
  • 36 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 37 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
  • 38 Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
  • 39 Leuven Multidisciplinary Breast Center, Department of Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
  • 40 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia
  • 41 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
  • 42 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 43 Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland
  • 44 Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway
  • 45 Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA
  • 46 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK
  • 47 Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 48 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
  • 49 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland
  • 50 Division of Breast Cancer Research, The Institute of Cancer Research, London, UK
  • 51 Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain
  • 52 Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • 53 Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland
  • 54 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
  • 55 National Cancer Institute, Bangkok, Thailand
  • 56 Research Oncology, Guy's Hospital, King's College London, London, UK
  • 57 School of Public Health, China Medical University, Taichung, Taiwan
  • 58 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA
  • 59 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada
  • 60 Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Australia
  • 61 Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia
  • 62 McGill University and Génome Québec Innovation Centre, Montréal, Canada
  • 63 Research and Technology Assessment Department, National Cancer Institute, Thailand
  • 64 Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
  • 65 Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research "Demokritos", Athens, Greece
  • 66 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK
Sci Rep, 2016 Nov 15;6:36874.
PMID: 27845421 DOI: 10.1038/srep36874

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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