Fulltext

Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3

Hamdi Y 1 , Soucy P 1 , Kuchenbaeker KB 2 , Pastinen T 3 , Droit A 1 , Lemaçon A 1 Show all authors , Adlard J 4 , Aittomäki K 5 , Andrulis IL 6 , Arason A 7 , Arnold N 8 , Arun BK 9 , Azzollini J 10 , Bane A 11 , Barjhoux L 12 , Barrowdale D 2 , Benitez J 13 , Berthet P 14 , Blok MJ 15 , Bobolis K 16 , Bonadona V 17 , Bonanni B 18 , Bradbury AR 19 , Brewer C 20 , Buecher B 21 , Buys SS 22 , Caligo MA 23 , Chiquette J 24 , Chung WK 25 , Claes KB 26 , Daly MB 27 , Damiola F 12 , Davidson R 28 , De la Hoya M 29 , De Leeneer K 26 , Diez O 30 , Ding YC 31 , Dolcetti R 32 , Domchek SM 19 , Dorfling CM 33 , Eccles D 34 , Eeles R 35 , Einbeigi Z 36 , Ejlertsen B 37 , EMBRACE , Engel C 38 , Gareth Evans D 39 , Feliubadalo L 40 , Foretova L 41 , Fostira F 42 , Foulkes WD 43 , Fountzilas G 44 , Friedman E 45 , Frost D 2 , Ganschow P 46 , Ganz PA 47 , Garber J 48 , Gayther SA 49 , GEMO Study Collaborators , Gerdes AM 50 , Glendon G 6 , Godwin AK 51 , Goldgar DE 52 , Greene MH 53 , Gronwald J 54 , Hahnen E 55 , Hamann U 56 , Hansen TV 57 , Hart S 58 , Hays JL 59 , HEBON , Hogervorst FB 60 , Hulick PJ 61 , Imyanitov EN 62 , Isaacs C 63 , Izatt L 64 , Jakubowska A 54 , James P 65 , Janavicius R 66 , Jensen UB 67 , John EM 68 , Joseph V 69 , Just W 70 , Kaczmarek K 54 , Karlan BY 71 , KConFab Investigators , Kets CM 72 , Kirk J 73 , Kriege M 74 , Laitman Y 45 , Laurent M 21 , Lazaro C 40 , Leslie G 2 , Lester J 71 , Lesueur F 75 , Liljegren A 76 , Loman N 77 , Loud JT 53 , Manoukian S 10 , Mariani M 10 , Mazoyer S 78 , McGuffog L 2 , Meijers-Heijboer HE 79 , Meindl A 8 , Miller A 80 , Montagna M 81 , Mulligan AM 82 , Nathanson KL 19 , Neuhausen SL 31 , Nevanlinna H 83 , Nussbaum RL 84 , Olah E 85 , Olopade OI 86 , Ong KR 87 , Oosterwijk JC 88 , Osorio A 13 , Papi L 89 , Park SK 90 , Pedersen IS 91 , Peissel B 10 , Segura PP 92 , Peterlongo P 93 , Phelan CM 94 , Radice P 95 , Rantala J 96 , Rappaport-Fuerhauser C 97 , Rennert G 98 , Richardson A 99 , Robson M 100 , Rodriguez GC 101 , Rookus MA 102 , Schmutzler RK 55 , Sevenet N 103 , Shah PD 19 , Singer CF 97 , Slavin TP 46 , Snape K 104 , Sokolowska J 105 , Sønderstrup IM 106 , Southey M 107 , Spurdle AB 108 , Stadler Z 109 , Stoppa-Lyonnet D 21 , Sukiennicki G 54 , Sutter C 110 , Tan Y 97 , Tea MK 97 , Teixeira MR 111 , Teulé A 112 , Teo SH 113 , Terry MB 114 , Thomassen M 115 , Tihomirova L 116 , Tischkowitz M 43 , Tognazzo S 81 , Toland AE 117 , Tung N 118 , van den Ouweland AM 119 , van der Luijt RB 120 , van Engelen K 121 , van Rensburg EJ 33 , Varon-Mateeva R 122 , Wappenschmidt B 55 , Wijnen JT 123 , Rebbeck T 19 , Chenevix-Trench G 108 , Offit K 69 , Couch FJ 58 , Nord S 124 , Easton DF 2 , Antoniou AC 2 , Simard J 125

Affiliations 

  • 1 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, 2705 Laurier Boulevard, Quebec, QC, G1V 4G2, Canada
  • 2 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK
  • 3 Department of Human Genetics, McGill University, Montreal, QC, H3A 1B1, Canada
  • 4 Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, LS7 4SA, UK
  • 5 Department of Clinical Genetics, Helsinki University Hospital, HUS, Meilahdentie 2, P.O. BOX 160, 00029, Helsinki, Finland
  • 6 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada
  • 7 Department of Pathology hus 9, Landspitali-LSH v/Hringbraut, 101, Reykjavík, Iceland
  • 8 Department of Gynaecology and Obstetrics, University Hospital of Schleswig-Holstein, Christian-Albrechts University Kiel, Campus Kiel, 24105, Kiel, Germany
  • 9 Department of Breast Medical Oncology and Clinical Cancer Genetics Program, University of Texas MD Anderson Cancer Center, 1515 Pressler Street CBP 5, Houston, TX, 77030, USA
  • 10 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), Via Giacomo Venezian 1, 20133, Milan, Italy
  • 11 Department of Pathology & Molecular Medicine, Juravinski Hospital and Cancer Centre, McMaster University, 711 Concession Street, Hamilton, ON, L8V 1C3, Canada
  • 12 Bâtiment Cheney D, Centre Léon Bérard, 28 rue Laënnec, 69373, Lyon, France
  • 13 Human Genetics Group, Spanish National Cancer Centre (CNIO), Madrid, Spain
  • 14 Centre François Baclesse, 3 avenue Général Harris, 14076, Caen, France
  • 15 Department of Clinical Genetics, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands
  • 16 City of Hope Clinical Cancer Genomics Community Research Network, 1500 East Duarte Road, Duarte, CA, 91010, USA
  • 17 Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, 28 rue Laënnec, 69373, Lyon, France
  • 18 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Via Ripamonti 435, 20141, Milan, Italy
  • 19 Department of Medicine, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA
  • 20 Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, EX1 2ED, UK
  • 21 Service de Génétique Oncologique, Institut Curie, 26 rue d'Ulm, 75248, Paris Cedex 05, France
  • 22 Department of Medicine, Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA
  • 23 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, Pisa, Italy
  • 24 Unité de recherche en santé des populations, Centre des maladies du sein Deschênes-Fabia, Hôpital du Saint-Sacrement, 1050 chemin Sainte-Foy, Quebec, QC, G1S 4L8, Canada
  • 25 Departments of Pediatrics and Medicine, Columbia University, 1150 St. Nicholas Avenue, New York, NY, 10032, USA
  • 26 Center for Medical Genetics, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium
  • 27 Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA
  • 28 Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow, G51 4TF, UK
  • 29 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Martin Lagos s/n, Madrid, Spain
  • 30 Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Clinical and Molecular Genetics Area, Passeig Vall d'Hebron 119-129, 08035, Barcelona, Spain
  • 31 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
  • 32 Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) National Cancer Institute, Via Franco Gallini 2, 33081, Aviano, PN, Italy
  • 33 Cancer Genetics Laboratory, Department of Genetics, University of Pretoria, Private Bag X323, Arcadia, 0007, South Africa
  • 34 Faculty of Medicine, University of Southampton, Southampton University Hospitals NHS Trust, Southampton, UK
  • 35 Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, SM2 5NG, UK
  • 36 Department of Oncology, Sahlgrenska University Hospital, 41345, Göteborg, Sweden
  • 37 Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark
  • 38 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany
  • 39 Genomic Medicine, Manchester Academic Health Sciences Centre, Institute of Human Development, Manchester University, Central Manchester University Hospitals, NHS Foundation Trust, Manchester, M13 9WL, UK
  • 40 Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Gran Via de l'Hospitalet, 199-203, L'Hospitalet, 08908, Barcelona, Spain
  • 41 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653, Brno, Czech Republic
  • 42 Molecular Diagnostics Laboratory, (INRASTES) Institute of Nuclear and Radiological Sciences and Technology, National Centre for Scientific Research "Demokritos", Patriarchou Gregoriou & Neapoleos str., Aghia Paraskevi Attikis, Athens, Greece
  • 43 Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, QC, Canada
  • 44 Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloníki, Greece
  • 45 The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Chaim Sheba Medical Center, 52621, Ramat Gan, Israel
  • 46 Clinical Cancer Genetics, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA
  • 47 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, 650 Charles Young Drive South, Room A2-125 HS, Los Angeles, CA, 90095-6900, USA
  • 48 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, USA
  • 49 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA
  • 50 Department of Clincial Genetics, Rigshospitalet, Blegdamsvej 9, 4062, Copenhagen, Denmark
  • 51 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, 4019 Wahl Hall East, MS 3040, Kansas City, Kansas, USA
  • 52 Department of Dermatology, University of Utah School of Medicine, 30 North 1900 East, SOM 4B454, Salt Lake City, UT, 84132, USA
  • 53 Clinical Genetics Branch, DCEG, NCI NIH, 9609 Medical Center Drive, Room 6E-454, Bethesda, MD, USA
  • 54 Department of Genetics and Pathology, Pomeranian Medical University, Polabska 4, 70-115, Szczecin, Poland
  • 55 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931, Cologne, Germany
  • 56 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany
  • 57 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark
  • 58 Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
  • 59 Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, 43210, USA
  • 60 Family Cancer Clinic, Netherlands Cancer Institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands
  • 61 Center for Medical Genetics, NorthShore University HealthSystem, University of Chicago Pritzker School of Medicine, 1000 Central Street, Suite 620, Evanston, IL, 60201, USA
  • 62 N.N. Petrov Institute of Oncology, St. Petersburg, Russia, 197758
  • 63 Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC, 20007, USA
  • 64 Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT, UK
  • 65 Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia
  • 66 Hematology, Oncology and Transfusion Medicine Center, Department of Molecular and Regenerative Medicine, Vilnius University Hospital Santariskiu Clinics, Santariskiu st. 2, 08661, Vilnius, Lithuania
  • 67 Department of Clinical Genetics, Aarhus University Hospital, Brendstrupgaardsvej 21C, Århus N, Denmark
  • 68 Department of Epidemiology, Cancer Prevention Institute of California, 2201 Walnut Avenue Suite 300, Fremont, CA, 94538, USA
  • 69 Clinical Genetics Research Laboratory, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10044, USA
  • 70 Institute of Human Genetics, University of Ulm, 89091, Ulm, Germany
  • 71 Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 290W, Los Angeles, CA, 90048, USA
  • 72 Department of Human Genetics, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
  • 73 Westmead Hospital, Familial Cancer Service, Hawkebury Road, P.O. Box 533, Wentworthville, NSW, 2145, Australia
  • 74 Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, P.O. Box 5201, 3008 AE, Rotterdam, The Netherlands
  • 75 Genetic Epidemiology of Cancer Team, INSERM U900, Institut Curie Mines ParisTech, PSL University, 26 rue d'Ulm, 75248, Paris Cedex 05, France
  • 76 Department of Oncology, Karolinska University Hospital, 17176, Stockholm, Sweden
  • 77 Department of Oncology, Lund University Hospital, 22185, Lund, Sweden
  • 78 Lyon Neuroscience Research Center-CRNL, INSERM U1028, CNRS UMR5292, University of Lyon, Lyon, France
  • 79 Department of Clinical Genetics, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands
  • 80 NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Elm St & Carlton St, Buffalo, NY, 14263, USA
  • 81 Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128, Padua, Italy
  • 82 Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • 83 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Biomedicum Helsinki, Haartmaninkatu 8, HUS, P.O. BOX 700, 00029, Helsinki, Finland
  • 84 Department of Medicine and Genetics, University of California, 513 Parnassus Ave., HSE 901E, San Francisco, CA, 94143-0794, USA
  • 85 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
  • 86 Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL, USA
  • 87 West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK
  • 88 Department of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB, Groningen, The Netherlands
  • 89 Unit of Medical Genetics, Department of Biomedical Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134, Florence, Italy
  • 90 Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Korea
  • 91 Section of Molecular Diagnostics, Department of Biochemistry, Aalborg University Hospital, Reberbansgade 15, Ålborg, Denmark
  • 92 Department of Oncology, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Martin Lagos s/n, Madrid, Spain
  • 93 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, c/o IFOM-IEO Campus, Via Adamello 16, 20139, Milan, Italy
  • 94 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, 33612, USA
  • 95 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predicted Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), c/o Amaedeolab via GA Amadeo 42, 20133, Milan, Italy
  • 96 Department of Clinical Genetics, Karolinska University Hospital, L5:03, 171 76, Stockholm, Sweden
  • 97 Department of OB/GYN, Medical University of Vienna, Waehringer Guertel 18-20, A, 1090, Vienna, Austria
  • 98 Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, 7 Michal St., 34362, Haifa, Israel
  • 99 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  • 100 Clinical Genetics, Services Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA
  • 101 Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, 2650 Ridge Avenue, Suite 1507, Walgreens, Evanston, IL, 60201, USA
  • 102 Department of Epidemiology, Netherlands Cancer Institute, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands
  • 103 Oncogénétique, Institut Bergonié, 229 cours de l'Argonne, 33076, Bordeaux, France
  • 104 Medical Genetics Unit, St George's, University of London, London, SW17 0RE, UK
  • 105 Laboratoire de génétique médicale Nancy Université, Centre Hospitalier Régional et Universitaire, Rue du Morvan cedex 1, 54511, Vandoeuvre-les-Nancy, France
  • 106 Department of Pathology Region Zealand Section Slagelse, Slagelse Hospital, Ingemannsvej 18 Slagelse, Cpoenhagen, Denmark
  • 107 Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, 3010, Australia
  • 108 Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Herston Road, Brisbane, QLD, 4006, Australia
  • 109 Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA
  • 110 Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
  • 111 Department of Genetics, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal
  • 112 Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Gran Via de l'Hospitalet, 199-203, L'Hospitalet, 08908, Barcelona, Spain
  • 113 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 1 Jalan SS12/1A, 47500, Subang Jaya, Malaysia
  • 114 Department of Epidemiology, Columbia University, New York, NY, USA
  • 115 Department of Clinical Genetics, Odense University Hospital, Sonder Boulevard 29, Odense C, Denmark
  • 116 Latvian Biomedical Research and Study Centre, Ratsupites str 1, Riga, Latvia
  • 117 Division of Human Genetics, Departments of Internal Medicine and Cancer Biology and Genetics Comprehensive Cancer Center, The Ohio State University, 998 Biomedical Research Tower, Columbus, OH, 43210, USA
  • 118 Department of Medical Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA
  • 119 Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, 330 Brookline Avenue, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
  • 120 Department of Medical Genetics, University Medical Center Utrecht, 3584 EA, Utrecht, The Netherlands
  • 121 Department of Clinical Genetics, Academic Medical Center, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands
  • 122 Institute of Human Genetics, Charite Berlin, Campus Virchov Klinikum, 13353, Berlin, Germany
  • 123 Department of Human Genetics & Department of Clinical Genetics, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands
  • 124 Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, 0372, Oslo, Norway
  • 125 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, 2705 Laurier Boulevard, Quebec, QC, G1V 4G2, Canada. Jacques.Simard@crchudequebec.ulaval.ca
Breast Cancer Res Treat, 2017 01;161(1):117-134.
PMID: 27796716 DOI: 10.1007/s10549-016-4018-2

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications