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

Jingjing Liu, Ivona Loncar, J. Margriet Colleé, Manjeet K. Bolla, Joe Dennis, Kyriaki Michailidou, Qin Wang, Irene L Andrulis, Monica Barile, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Carl Blomqvist, Bram Boeckx, Natalia V. Bogdanova, Stig E Bojesen, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Annegien BroeksBarbara Burwinkel, Jenny Chang-Claude, Shou-Tung Chen, Georgia Chenevix-Trench, Ching-Yu Cheng, Ji Yeob Choi, Fergus J Couch, Angela Cox, Simon S Cross, Katarina Cuk, Kamila Czene, Thilo Dörk, Isabel Dos-Santos-Silva, Peter A. Fasching, Jonine D Figueroa, Henrik Flyger, Montserrat Garciá-Closas, Graham G. Giles, Gord Glendon, Mark S. Goldberg, Anna González-Neira, Pascal Guénel, Christopher A Haiman, Ute Hamann, Steven N. Hart, Mikael Hartman, Sigrid Hatse, John L. Hopper, Hidemi Ito, Anna Jakubowska, Maria Kabisch, Daehee Kang, Veli-Matti Kosma, Vessela N. Kristensen, Loic Le Marchand, Eunjung Lee, Jingmei Li, Artitaya Lophatananon, Jan Lubinski, Arto Mannermaa, Keitaro Matsuo, Roger L. Milne, Susan L Neuhausen, Heli Nevanlinna, Nick Orr, Jose Ignacio Arias Perez, Julian Peto, Thomas Choudary Putti, Katri Pylkäs, Paolo Radice, Suleeporn Sangrajrang, Elinor J Sawyer, Marjanka K. Schmidt, Andreas Schneeweiss, Chen-Yang Shen, Martha J. Shrubsole, Xiao-Ou Shu, Jacques Simard, Melissa C. Southey, Anthony J Swerdlow, Soo-Hwang Teo, Daniel C. Tessier, Somchai Thanasitthichai, Ian P Tomlinson, Diana Torres, Thérèse Truong, Chiu-Chen Tseng, Celine M Vachon, Robert Winqvist, Anna H Wu, Drakoulis Yannoukakos, Wei Zheng, Per Hall, Alison M Dunning, Douglas F Easton, Maartje J Hooning, Ans M W van den Ouweland, John W M Martens, Antoinette Hollestelle, NBCS Collaborators

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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.

Original languageEnglish
Article number36874
Number of pages13
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 15 Nov 2016
Externally publishedYes

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