Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.

Original publication

DOI

10.1016/j.ajhg.2013.01.002

Type

Journal article

Journal

American journal of human genetics

Publication Date

04/2013

Volume

92

Pages

489 - 503

Addresses

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.

Keywords

GENICA Network, kConFab Investigators, Cell Line, Tumor, Chromosomes, Human, Pair 11, Chromatin, Humans, Breast Neoplasms, Luciferases, Cyclin D1, RNA, Small Interfering, RNA, Messenger, Electrophoretic Mobility Shift Assay, Case-Control Studies, Chromatin Immunoprecipitation, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Regulation, Neoplastic, Binding Sites, Silencer Elements, Transcriptional, Polymorphism, Single Nucleotide, Female, ets-Domain Protein Elk-4, GATA3 Transcription Factor, Enhancer Elements, Genetic, Promoter Regions, Genetic, Real-Time Polymerase Chain Reaction