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

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 (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 7

Pages Range: 80140-80163

Journal Issue: 49

DOI: 10.18632/oncotarget.12818

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.

Authors with CRIS profile

Involved external institutions

Université Laval (UL) CA Canada (CA) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) University of Cambridge GB United Kingdom (GB) Antoni van Leeuwenhoek NL Netherlands (NL) Mount Sinai Hospital (MSH) CA Canada (CA) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Helsingin yliopisto / University of Helsinki FI Finland (FI) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Copenhagen University Hospital DK Denmark (DK) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) IT Italy (IT) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO) Karolinska Institute SE Sweden (SE) Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Mayo Clinic US United States (USA) (US) University of Sheffield GB United Kingdom (GB) Leiden University NL Netherlands (NL) University of Edinburgh GB United Kingdom (GB) National Cancer Institute (NCI) US United States (USA) (US) Cancer Council Victoria AU Australia (AU) McGill University CA Canada (CA) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) ES Spain (ES) École Polytechnique - Université Paris-Saclay FR France (FR) University of Southern California (USC) US United States (USA) (US) Erasmus University Medical Center (MC) NL Netherlands (NL) The University of Melbourne AU Australia (AU) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) PL Poland (PL) The Institute of Cancer Research (ICR) GB United Kingdom (GB) University of Eastern Finland FI Finland (FI) Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC)) BE Belgium (BE) University of Hawaii (U.H.) US United States (USA) (US) Beckman Research Institute of City of Hope (BRI) US United States (USA) (US) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven BE Belgium (BE) Mazedonische Akademie der Wissenschaften und Künste MK Republic of North Macedonia (MK) Oulun Yliopisto / University of Oulo FI Finland (FI) King’s College London GB United Kingdom (GB) Vanderbilt University US United States (USA) (US) University of Oxford GB United Kingdom (GB) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam NL Netherlands (NL) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) NordLab FI Finland (FI)

How to cite

APA:

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. https://dx.doi.org/10.18632/oncotarget.12818

MLA:

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.

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