rs2735383, located at a microRNA binding site in the 3’UTR of NBS1, is not associated with breast cancer risk
Authors: Liu Jingjing , Lončar Ivona , Collée J. Margriet , Bolla Manjeet K. , Dennis Joe , Michailidou Kyriaki , Wang Qin , Andrulis Irene L. , Barile Monica , Beckmann Matthias W. , Behrens Sabine , Benitez Javier , Blomqvist Carl , Boeckx Bram , Bogdanova Natalia V. , Bojesen Stig E. , Brauch Hiltrud , Brennan Paul , Brenner Hermann , Broeks Annegien , Burwinkel Barbara , Chang-Claude Jenny , Chen Shou-Tung , Chenevix-Trench Georgia , Cheng Ching Y. , Choi Ji-Yeob , Couch Fergus J. , Cox Angela , Cross Simon S. , Cuk Katarina , Czene Kamila , Dörk Thilo , dos-Santos-Silva Isabel , Fasching Peter A. , Figueroa Jonine , Flyger Henrik , García-Closas Montserrat , Giles Graham G. , Glendon Gord , Goldberg Mark S. , González-Neira Anna , Guénel Pascal , Haiman Christopher A. , Hamann Ute , Hart Steven N. , Hartman Mikael , Hatse Sigrid , Hopper John L. , Ito Hidemi , Jakubowska Anna , Kabisch Maria , Kang Daehee , Kosma Veli-Matti , Kristensen Vessela N. , Le Marchand Loic , Lee Eunjung , Li Jingmei , Lophatananon Artitaya , Jan Lubinski  , Mannermaa Arto , Matsuo Keitaro , Milne Roger L. ,   NBCS Collaborators, Sahlberg Kristine K. , Ottestad Lars , Kåresen Rolf , Langerød Anita , Schlichting Ellen , Holmen Marit Muri , Sauer Toril , Haakensen Vilde , Engebråten Olav , Naume Bjørn , Kiserud Cecile E. , Reinertsen Kristin V. , Helland åslaug , Riis Margit , Bukholm Ida , Lønning Per Eystein , Børresen-Dale Anne-Lise , Grenaker Alnæs Grethe I. , Neuhausen Susan L. , Nevanlinna Heli , Orr Nick , Perez Jose I. A. , Peto Julian , Putti Thomas C. , Pylkäs Katri , Radice Paolo , Sangrajrang Suleeporn , Sawyer Elinor J. , Schmidt Marjanka K. , Schneeweiss Andreas , Shen Chen-Yang , Shrubsole Martha J. , Shu Xiao-Ou , Simard Jacques , Southey Melissa C. , Swerdlow Anthony , Teo Soo H. , Tessier Daniel C. , Thanasitthichai Somchai , Tomlinson Ian , Torres Diana , Truong Thérèse , Tseng Chiu-Chen , Vachon Celine , Winqvist Robert , Wu Anna H. , Yannoukakos Drakoulis , Zheng Wei , Hall Per , Dunning Alison M. , Easton Douglas F. , Hooning Maartje J. , van den Ouweland Ans M. W. , Martens John W. M. , Hollestelle Antoinette 
Published: November 2016

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.