Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01

AUTHORS

Yosr Hamdi, Penny Soucy, Karoline B. Kuchenbaeker, Tomi Pastinen, Arnaud Droit, Audrey Lemaçon, Julian Adlard, Kristiina Aittomäki, Irene L. Andrulis, Adalgeir Arason, Norbert Arnold, Banu K. Arun, Jacopo Azzollini, Anita Bane, Laure Barjhoux, Daniel Barrowdale, Javier Benitez, Pascaline Berthet, Marinus J. Blok, Kristie Bobolis, Valérie Bonadona, Bernardo Bonanni, Angela R. Bradbury, Carole Brewer, Bruno Buecher, Saundra S. Buys, Maria A. Caligo, Jocelyne Chiquette, Wendy K. Chung, Kathleen B. M. Claes, Mary B. Daly, Francesca Damiola, Rosemarie Davidson, Miguel De la Hoya, Kim De Leeneer, Orland Diez, Yuan Chun Ding, Riccardo Dolcetti, Susan M. Domchek, Cecilia M. Dorfling, Diana Eccles, Ros Eeles, Zakaria Einbeigi, Bent Ejlertsen, EMBRACE, Christoph Engel, D. Gareth Evans, Lidia Feliubadalo, Lenka Foretova, Florentia Fostira, William D. Foulkes, George Fountzilas, Eitan Friedman, Debra Frost, Pamela Ganschow, Patricia A. Ganz, Judy Garber, Simon A. Gayther, GEMO Study Collaborators, Anne-Marie Gerdes, Gord Glendon, Andrew K. Godwin, David E. Goldgar, Mark H. Greene, Jacek Gronwald, Eric Hahnen, Ute Hamann, Thomas V. O. Hansen, Steven Hart, John L. Hays, HEBON, Frans B. L. Hogervorst, Peter J. Hulick, Evgeny N. Imyanitov, Claudine Isaacs, Louise Izatt, Anna Jakubowska, Paul James, Ramunas Janavicius, Uffe Birk Jensen, Esther M. John, Vijai Joseph, Walter Just, Katarzyna Kaczmarek, Beth Y. Karlan, KConFab Investigators, Carolien M. Kets, Judy Kirk, Mieke Kriege, Yael Laitman, Maïté Laurent, Conxi Lazaro, Goska Leslie, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Niklas Loman, Jennifer T. Loud, Siranoush Manoukian, Milena Mariani, Sylvie Mazoyer, Lesley McGuffog, Hanne E. J. Meijers-Heijboer, Alfons Meindl, Austin Miller, Marco Montagna, Anna Marie Mulligan, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Robert L. Nussbaum, Edith Olah, Olufunmilayo I. Olopade, Kai-ren Ong, Jan C. Oosterwijk, Ana Osorio, Laura Papi, Sue Kyung Park, Inge Sokilde Pedersen, Bernard Peissel, Pedro Perez Segura, Paolo Peterlongo, Catherine M. Phelan, Paolo Radice, Johanna Rantala, Christine Rappaport-Fuerhauser, Gad Rennert, Andrea Richardson, Mark Robson, Gustavo C. Rodriguez, Matti A. Rookus, Rita Katharina Schmutzler, Nicolas Sevenet, Payal D. Shah, Christian F. Singer, Thomas P. Slavin, Katie Snape, Johanna Sokolowska, Ida Marie Heeholm Sønderstrup, Melissa Southey, Amanda B. Spurdle, Zsofia Stadler, Dominique Stoppa-Lyonnet, Grzegorz Sukiennicki, Christian Sutter, Yen Tan, Muy-Kheng Tea, Manuel R. Teixeira, Alex Teulé, Soo-Hwang Teo, Mary Beth Terry, Mads Thomassen, Laima Tihomirova, Marc Tischkowitz, Silvia Tognazzo, Amanda Ewart Toland, Nadine Tung, Ans M. W. van den Ouweland, Rob B. van der Luijt, Klaartje van Engelen, Elizabeth J. van Rensburg, Raymonda Varon-Mateeva, Barbara Wappenschmidt, Juul T. Wijnen, Timothy Rebbeck, Georgia Chenevix-Trench, Kenneth Offit, Fergus J. Couch, Silje Nord, Douglas F. Easton, Antonis C. Antoniou, Jacques Simard

ABSTRACT

PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk. More... »

PAGES

117-134

Journal

TITLE

Breast Cancer Research and Treatment

ISSUE

1

VOLUME

161

Author Affiliations

  • Wellcome Sanger Institute
  • McGill University and Génome Québec Innovation Centre
  • Chapel Allerton Hospital
  • Helsinki University Central Hospital
  • University of Toronto
  • University of Iceland
  • The University of Texas MD Anderson Cancer Center
  • McMaster University
  • Centre Léon Bérard
  • University of Cambridge
  • Spanish National Cancer Research Centre
  • Centre Franois Baclesse
  • Maastricht University Medical Centre
  • City Of Hope National Medical Center
  • European Institute of Oncology
  • Royal Devon and Exeter Hospital
  • Institute Curie
  • Huntsman Cancer Institute
  • Azienda Ospedaliera Universitaria Pisana
  • Hôpital du Saint-Sacrement
  • Columbia University
  • Ghent University
  • Temple University Health System
  • University of Glasgow
  • Hospital Clínico San Carlos
  • Hospital Universitari Vall d'Hebron
  • University of Queensland
  • University of Pretoria
  • Sahlgrenska University Hospital
  • Leipzig University
  • University of Manchester
  • Masaryk Memorial Cancer Institute
  • National Centre of Scientific Research Demokritos
  • McGill University
  • Aristotle University of Thessaloniki
  • Tel Aviv University
  • University of California Los Angeles
  • Dana–Farber Cancer Institute
  • University of Southern California
  • Paris Descartes University
  • Rigshospitalet
  • University of Kansas Medical Center
  • University of Utah
  • National Cancer Institute
  • Pomeranian Medical University
  • University Hospital Cologne
  • German Cancer Research Center
  • Mayo Clinic
  • The Ohio State University
  • Antoni van Leeuwenhoek Hospital
  • NorthShore University HealthSystem
  • Institute of Oncology NN Petrov
  • Georgetown University
  • Guy's and St Thomas' NHS Foundation Trust
  • University of Melbourne
  • State Research Institute Centre for Innovative Medicine
  • Aarhus University Hospital
  • Stanford University
  • Memorial Sloan Kettering Cancer Center
  • University of Ulm
  • Cedars-Sinai Medical Center
  • Peter MacCallum Cancer Centre
  • Radboud University Nijmegen Medical Centre
  • Westmead Hospital
  • Erasmus University Medical Center
  • Sheba Medical Center
  • Karolinska University Hospital
  • Skåne University Hospital
  • University of Lyon System
  • VU University Medical Center
  • Roswell Park Cancer Institute
  • St. Michael's Hospital
  • University of California, San Francisco
  • National Institute of Oncology
  • Centre for Biomedical Network Research on Rare Diseases
  • University of Florence
  • Seoul National University
  • Aalborg Hospital
  • Moffitt Cancer Center
  • Medical University of Vienna
  • Johns Hopkins University
  • Institut Bergonié
  • University College London
  • Slagelse Hospital
  • QIMR Berghofer Medical Research Institute
  • University Hospital Heidelberg
  • University of Porto
  • University of Malaya
  • Odense University Hospital
  • Latvian Biomedical Research and Study Centre
  • Addenbrooke's Hospital
  • Beth Israel Deaconess Medical Center
  • University Medical Center Utrecht
  • Academic Medical Center
  • Charité
  • Leiden University Medical Center
  • University of Pennsylvania
  • Oslo University Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10549-016-4018-2

    DOI

    http://dx.doi.org/10.1007/s10549-016-4018-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1045330156

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27796716


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