TY - JOUR
T1 - rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk
AU - Liu, Jingjing
AU - Lončar, Ivona
AU - Collée, J Margriet
AU - Bolla, Manjeet K
AU - Dennis, Joe
AU - Michailidou, Kyriaki
AU - Wang, Qin
AU - Andrulis, Irene L
AU - Barile, Monica
AU - Beckmann, Matthias W
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Blomqvist, Carl
AU - Boeckx, Bram
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Brauch, Hiltrud
AU - Brennan, Paul
AU - Brenner, Hermann
AU - Broeks, Annegien
AU - Burwinkel, Barbara
AU - Chang-Claude, Jenny
AU - Chen, Shou-Tung
AU - Chenevix-Trench, Georgia
AU - Cheng, Ching Y
AU - Choi, Ji-Yeob
AU - Couch, Fergus J
AU - Cox, Angela
AU - Cross, Simon S
AU - Cuk, Katarina
AU - Czene, Kamila
AU - Dörk, Thilo
AU - Dos-Santos-Silva, Isabel
AU - Fasching, Peter A
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - García-Closas, Montserrat
AU - Giles, Graham G
AU - Glendon, Gord
AU - Goldberg, Mark S
AU - González-Neira, Anna
AU - Guénel, Pascal
AU - Haiman, Christopher A
AU - Hamann, Ute
AU - Hart, Steven N
AU - Hartman, Mikael
AU - Hatse, Sigrid
AU - Hopper, John L
AU - Ito, Hidemi
AU - Jakubowska, Anna
AU - NBCS Collaborators
PY - 2016/11/15
Y1 - 2016/11/15
N2 - 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.
AB - 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.
U2 - 10.1038/srep36874
DO - 10.1038/srep36874
M3 - Journal article
C2 - 27845421
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 36874
ER -