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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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  • Jingjing Liu
  • Ivona Lončar
  • J Margriet Collée
  • 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 Broeks
  • Barbara Burwinkel
  • Jenny Chang-Claude
  • Shou-Tung Chen
  • Georgia Chenevix-Trench
  • Ching Y 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 Figueroa
  • Henrik Flyger
  • Montserrat García-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
  • NBCS Collaborators
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind6
Sider (fra-til)36874
ISSN2045-2322
DOI
StatusUdgivet - 15 nov. 2016

ID: 49420866