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

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 (r(2) > 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.

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Item Type:	Article
Authors/Creators:	Liu, J Lončar, I Collée, JM Bolla, MK Dennis, J Michailidou, K Wang, Q Andrulis, IL Barile, M Beckmann, MW Behrens, S Benitez, J Blomqvist, C Boeckx, B Bogdanova, NV Bojesen, SE Brauch, H Brennan, P Brenner, H Broeks, A Burwinkel, B Chang-Claude, J Chen, ST Chenevix-Trench, G Cheng, CY Choi, JY Couch, FJ Cox, A https://orcid.org/0000-0002-5138-1099 Cross, SS Cuk, K Czene, K Dörk, T Dos-Santos-Silva, I Fasching, PA Figueroa, J Flyger, H García-Closas, M Giles, GG Glendon, G Goldberg, MS González-Neira, A Guénel, P Haiman, CA Hamann, U Hart, SN Hartman, M Hatse, S Hopper, JL Ito, H Jakubowska, A Kabisch, M Kang, D Kosma, VM Kristensen, VN Le Marchand, L Lee, E Li, J Lophatananon, A Jan Lubinski Mannermaa, A Matsuo, K Milne, RL NBCS Collaborators Neuhausen, SL Nevanlinna, H Orr, N Perez, JI Peto, J Putti, TC Pylkäs, K Radice, P Sangrajrang, S Sawyer, EJ Schmidt, MK Schneeweiss, A Shen, CY Shrubsole, MJ Shu, XO Simard, J Southey, MC Swerdlow, A Teo, SH Tessier, DC Thanasitthichai, S Tomlinson, I Torres, D Truong, T Tseng, CC Vachon, C Winqvist, R Wu, AH Yannoukakos, D Zheng, W Hall, P Dunning, AM Easton, DF Hooning, MJ van den Ouweland, AM Martens, JW Hollestelle, A
Copyright, Publisher and Additional Information:	© Year The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Dates:	Published: 15 November 2016 Published (online): 15 October 2016 Accepted: 21 October 2016
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals
Funding Information:	Funder Grant number YORKSHIRE CANCER RESEARCH S299 CANCER RESEARCH UK (CRUK) C5410/A7315.
Depositing User:	Symplectic Sheffield
Date Deposited:	23 Nov 2016 15:25
Last Modified:	23 Nov 2016 15:25
Published Version:	http://doi.org/10.1038/srep36874
Status:	Published
Publisher:	Nature Publishing Group
Refereed:	Yes
Identification Number:	10.1038/srep36874
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:108215

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

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