Fulltext

Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer

Shi J 1 , Zhang Y 1 , Zheng W 1 , Michailidou K 2 , Ghoussaini M 3 , Bolla MK 2 Show all authors , Wang Q 2 , Dennis J 3 , Lush M 3 , Milne RL 4 , Shu XO 1 , Beesley J 5 , Kar S 3 , Andrulis IL 6 , Anton-Culver H 7 , Arndt V 8 , Beckmann MW 9 , Zhao Z 1 , Guo X 1 , Benitez J 10 , Beeghly-Fadiel A 1 , Blot W 1 , Bogdanova NV 11 , Bojesen SE 12 , Brauch H 13 , Brenner H 8 , Brinton L 14 , Broeks A 15 , Brüning T 16 , Burwinkel B 17 , Cai H 1 , Canisius S 18 , Chang-Claude J 19 , Choi JY 20 , Couch FJ 21 , Cox A 22 , Cross SS 23 , Czene K 24 , Darabi H 24 , Devilee P 25 , Droit A 26 , Dork T 27 , Fasching PA 9 , Fletcher O 28 , Flyger H 29 , Fostira F 30 , Gaborieau V 31 , García-Closas M 28 , Giles GG 4 , Mervi Grip , Guenel P 32 , Haiman CA 33 , Hamann U 34 , Hartman M 35 , Miao H 35 , Hollestelle A 36 , Hopper JL 37 , Hsiung CN 38 , kConFab Investigators , Ito H 39 , Jakubowska A 40 , Johnson N 28 , Torres D 34 , Kabisch M 34 , Kang D 20 , Khan S 41 , Knight JA 42 , Kosma VM 43 , Lambrechts D 44 , Li J 24 , Lindblom A 45 , Lophatananon A 46 , Lubinski J 40 , Mannermaa A 43 , Manoukian S 47 , Le Marchand L 48 , Margolin S 49 , Marme F 50 , Matsuo K 51 , McLean C 52 , Meindl A 37 , Muir K 46 , Neuhausen SL 53 , Nevanlinna H 41 , Nord S 54 , Børresen-Dale AL 54 , Olson JE 55 , Orr N 56 , van den Ouweland AMW 57 , Peterlongo P 58 , Putti TC 59 , Rudolph A 19 , Sangrajrang S 60 , Sawyer EJ 61 , Schmidt MK 15 , Schmutzler RK 62 , Shen CY 63 , Hou MF 64 , Shrubsole MJ 1 , Southey MC 65 , Swerdlow A 66 , Teo SH 67 , Thienpont B 44 , Toland AE 68 , Tollenaar RAEM 69 , Tomlinson I 70 , Truong T 32 , Tseng CC 33 , Wen W 1 , Winqvist R 71 , Wu AH 33 , Yip CH 72 , Zamora PM 73 , Zheng Y 74 , Floris G 75 , Cheng CY 76 , Hooning MJ 36 , Martens JWM 36 , Seynaeve C 36 , Kristensen VN 54 , Hall P 24 , Pharoah PDP 2 , Simard J 26 , Chenevix-Trench G 5 , Dunning AM 3 , Antoniou AC 2 , Easton DF 2 , Cai Q 1 , Long J 1

Affiliations 

  • 1 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA
  • 2 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
  • 3 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK
  • 4 Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Victoria 3053, Australia
  • 5 Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia
  • 6 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada
  • 7 Department of Epidemiology, University of California Irvine, Irvine, CA 92697, USA
  • 8 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg 69120, Germany
  • 9 Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen 91054, Germany
  • 10 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid 28029, Spain
  • 11 Department of Radiation Oncology, Hannover Medical School, Hannover 30625, Germany
  • 12 Copenhagen General Population Study, Herlev Hospital, 2730 Herlev, Denmark
  • 13 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart 70376, Germany
  • 14 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA
  • 15 Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam 1066 CX, The Netherlands
  • 16 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Bochum 44789, Germany
  • 17 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany
  • 18 Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, the Netherlands
  • 19 Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg 69120, Germany
  • 20 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea
  • 21 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
  • 22 Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield S10 2RX, UK
  • 23 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
  • 24 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-17177, Sweden
  • 25 Separtment of Pathology, Leiden University Medical Center, Leiden 2333 ZC, The Netherlands
  • 26 Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City G1V 4G2, Canada
  • 27 Gynaecology Research Unit, Hannover Medical School, Hannover 30625, Germany
  • 28 Division of Cancer Studies, Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK
  • 29 Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark
  • 30 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", 153 10 Athens, Greece
  • 31 International Agency for Research on Cancer, Lyon 69372, France
  • 32 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif 94807, France
  • 33 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
  • 34 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
  • 35 Saw Swee Hock School of Public Health, National University of Singapore, Singapore 119077, Singapore
  • 36 Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 CN Rotterdam, The Netherlands
  • 37 Division of Gynaecology and Obstetrics, Technische Universität München, Munich 81675, Germany
  • 38 Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
  • 39 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan
  • 40 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-115, Poland
  • 41 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, University of Helsinki, Helsinki, FI-00029 HUS, Finland
  • 42 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada
  • 43 School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine and Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finlan
  • 44 Vesalius Research Center, Leuven 3000, Belgium
  • 45 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm SE-17177, Sweden
  • 46 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK
  • 47 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan 20133, Italy
  • 48 University of Hawaii Cancer Center, Honolulu, HI 96813, USA
  • 49 Department of Oncology - Pathology, Karolinska Institutet, Stockholm SE-17177, Sweden
  • 50 National Center for Tumor Diseases, University of Heidelberg, Heidelberg 69120, Germany
  • 51 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan
  • 52 Anatomical Pathology, The Alfred Hospital, Melbourne, , Victoria 3004, Australia
  • 53 Beckman Research Institute of City of Hope, Duarte, CA 91010, USA
  • 54 Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Ullernchausseen 70, N-0310 Oslo, Norway
  • 55 Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
  • 56 Division of Breast Cancer Research, Institute of Cancer Research, London, UK; Cancer Research, Institute of Cancer Research, London SW3 6JB, UK
  • 57 Department of Clinical Genetics, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands
  • 58 IFOM, the FIRC Institute of Molecular Oncology, Milan 20139, Italy
  • 59 Department of Pathology, National University Health System, Singapore 117597
  • 60 National Cancer Institute, Bangkok 10400, Thailand
  • 61 Research Oncology, Guy's Hospital, King's College London, London SE1 9RT, UK
  • 62 Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne 50931, Germany
  • 63 School of Public Health, China Medical University, Taichung 404, Taiwan
  • 64 Cancer Center and Department of Surgery, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
  • 65 Department of Pathology, The University of Melbourne, Melbourne, Victoria 3010, Australia
  • 66 Division of Genetics and Epidemiology and Division of Breast Cancer Research, Institute of Cancer Research, London SW7 3RP, UK
  • 67 Cancer Research Initiatives Foundation, 47500 Subang Jaya, Selangor, Malaysia
  • 68 Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
  • 69 Department of Surgical Oncology, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands
  • 70 Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK
  • 71 Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry, University of Oulu, Oulu FI-90220, Finland
  • 72 Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, 59100 KualaLumpur, Malaysia
  • 73 Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid 28046, Spain
  • 74 Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, PR China
  • 75 University Hospital Gashuisberg, Leuven, Belgium
  • 76 Singapore Eye Research Institute, National University of Singapore, Singapore, Singapore
Int J Cancer, 2016 Sep 15;139(6):1303-1317.
PMID: 27087578 DOI: 10.1002/ijc.30150

Abstract

Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

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

MeSH terms
Similar publications