Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21

Journal article

Publication Details

Author(s): Hamdi Y, Soucy P, Adoue V, Michailidou K, Canisius S, Lemacon A, Droit A, Andrulis IL, Anton-Culver H, Arndt V, Baynes C, Blomqvist C, Bogdanova NV, Bojesen SE, Bolla MK, Bonanni B, Borresen-Dale AL, Brand JS, Brauch H, Brenner H, Broeks A, Burwinkel B, Chang-Claude J, Couch FJ, Cox A, Cross SS, Czene K, Darabi H, Dennis J, Devilee P, Doerk T, Dos-Santos-Silva I, Eriksson M, Fasching P, Figueroa J, Flyger H, Garcia-Closas M, Giles GG, Goldberg MS, Gonzalez-Neira A, Grenaker-Alnaes G, Guenel P, Häberle L, Haiman CA, Hamann U, Hallberg E, Hooning MJ, Hopper JL, Jakubowska A, Jones M, Kabisch M, Kataja V, Lambrechts D, Le Marchand L, Lindblom A, Lubinski J, Mannermaa A, Maranian M, Margolin S, Marme F, Milne RL, Neuhausen SL, Nevanlinna H, Neven P, Olswold C, Peto J, Plaseska-Karanfilska D, Pylkaes K, Radice P, Rudolph A, Sawyer EJ, Schmidt MK, Shu XO, Southey MC, Swerdlow A, Tollenaar RAEM, Tomlinson I, Torres D, Truong T, Vachon C, Van Den Ouweland AMW, Wang Q, Winqvist R, Zheng W, Benitez J, Chenevix-Trench G, Dunning AM, Pharoah PDP, Kristensen V, Hall P, Easton DF, Pastinen T, Nord S, Simard J
Journal: Oncotarget
Publication year: 2016
Volume: 7
Journal issue: 49
Pages range: 80140-80163
ISSN: 1949-2553


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.

FAU Authors / FAU Editors

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

External institutions with authors

Antoni van Leeuwenhoek
Beckman Research Institute of City of Hope (BRI)
Cancer Council Victoria
Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC))
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie
École Polytechnique - Université Paris-Saclay
Erasmus University Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Helsingin yliopisto / University of Helsinki
Karolinska Institute
King’s College London
Leiden University
Mayo Clinic
Mazedonische Akademie der Wissenschaften und Künste
McGill University
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
Oslo University Hospital / Oslo Universitetssykehus
Oulun Yliopisto / University of Oulo
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
The Institute of Cancer Research (ICR)
The University of Melbourne
Université Laval (UL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Eastern Finland
University of Edinburgh
University of Hawaii (U.H.)
University of Oxford
University of Sheffield
University of Southern California (USC)
Vanderbilt University

How to cite

Hamdi, Y., Soucy, P., Adoue, V., Michailidou, K., Canisius, S., Lemacon, A.,... Simard, J. (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(49), 80140-80163.

Hamdi, Yosr, et al. "Association of breast cancer risk with genetic variants showing differential allelic expression: Identification of a novel breast cancer susceptibility locus at 4q21." Oncotarget 7.49 (2016): 80140-80163.


Last updated on 2019-25-04 at 15:08