Hamdi, Y., Soucy, P., Adoue, V. et al. (93 more authors) (2016) Association of Breast Cancer Risk with Genetic Variants Showing Differential Allelic Expression: Identification of a Novel Breast Cancer Susceptibility Locus at 4q21. Oncotarget, 7. pp. 80140-80163. ISSN 1949-2553
Abstract
There are significant inter-individual differences in the levels of gene expression. Through modulation of gene expression, cis-acting variants represent an important source of phenotypic variation. Consequently, cis-regulatory SNPs associated with differential allelic expression are functional candidates for further investigation as disease-causing variants. To investigate whether common variants associated with differential allelic expression were involved in breast cancer susceptibility, a list of genes was established on the basis of their involvement in cancer related pathways and/or mechanisms. Thereafter, using data from a genome-wide map of allelic expression associated SNPs, 313 genetic variants were selected and their association with breast cancer risk was then evaluated in 46,451 breast cancer cases and 42,599 controls of European ancestry ascertained from 41 studies participating in the Breast Cancer Association Consortium. The associations were evaluated with overall breast cancer risk and with estrogen receptor negative and positive disease. One novel breast cancer susceptibility locus on 4q21 (rs11099601) was identified (OR = 1.05, P = 5.6x10-6). rs11099601 lies in a 135 kb linkage disequilibrium block containing several genes, including, HELQ, encoding the protein HEL308 a DNA dependant ATPase and DNA Helicase involved in DNA repair, MRPS18C encoding the Mitochondrial Ribosomal Protein S18C and FAM175A (ABRAXAS), encoding a BRCA1 BRCT domain-interacting protein involved in DNA damage response and double-strand break (DSB) repair. Expression QTL analysis in breast cancer tissue showed rs11099601 to be associated with HELQ (P = 8.28x10-14), MRPS18C (P = 1.94x10-27) and FAM175A (P = 3.83x10-3), explaining about 20%, 14% and 1%, respectively of the variance inexpression of these genes in breast carcinomas.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Author(s). Oncotarget applies the Creative Commons Attribution License (CC BY) to all works we publish (https://creativecommons.org/licenses/by/3.0/). Under the CC BY, authors retain ownership of the copyright for their article, but authors allow anyone to download, reuse, reprint, modify, distribute, and/or copy articles in Oncotarget journal, so long as the original authors and source are cited. |
Keywords: | breast cancer; genetic susceptibility; association studies; differential allelic expression; cis-regulatory variants |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number YORKSHIRE CANCER RESEARCH S299 BREAST CANCER CAMPAIGN UNSPECIFIED BREAST CANCER CAMPAIGN TB2009SHEF CANCER RESEARCH UK (CRUK) C5410/A7315. BREAST CANCER CAMPAIGN UNSPECIFIED BREAST CANCER NOW UNSPECIFIED BREAST CANCER NOW UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Nov 2016 11:42 |
Last Modified: | 29 Jan 2018 10:50 |
Published Version: | http://www.impactjournals.com/oncotarget/index.php... |
Status: | Published |
Publisher: | Impact Journals |
Refereed: | Yes |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107713 |