title: 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.
abstract: Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.
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authors.lastname: Lindström
authors.affiliation: Human Genetics, Genome Institute of Singapore, 60 Biopolis Street 02-01, Singapore 138672, Singapore.
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authors.affiliation: Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton SO16 6YD, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, The Netherlands.
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authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute, Postbus 90203, 1006 BE Amsterdam, The Netherlands.
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authors.affiliation: Department of Surgery, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
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authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Level 1, 723 Swanston Street, Melbourne, Victoria 3010, Australia.
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authors.affiliation: University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Universitätsstrasse 21-23, 91054 Erlangen, Germany.
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authors.affiliation: University Breast Center Franconia, Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Universitätsstrasse 21-23, 91054 Erlangen, Germany.
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authors.affiliation: Department of Oncology, University of Helsinki and Helsinki University Central Hospital, FI-00029 HUS Helsinki, Finland.
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authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FI-00029 Helsinki, Finland.
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authors.affiliation: Department of Clinical Genetics, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FI-00029 Helsinki, Finland.
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authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm SE-17177, Sweden.
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authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE-17177, Sweden.
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authors.affiliation: Department of Oncology, St Vincent's Hospital Melbourne, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
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authors.forename: Dieter
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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authors.affiliation: University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, Hawaii 96813, USA.
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authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1975 San Pablo Street, Los Angeles, California 90033, USA.
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authors.affiliation: 1] Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Ullernchausseen 70, N-0310 Oslo, Norway [2] K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway.
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authors.affiliation: 1] Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Ullernchausseen 70, N-0310 Oslo, Norway [2] K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway.
authors.forename: Anne-Lise
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authors.affiliation: 1] Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Ullernchausseen 70, N-0310 Oslo, Norway [2] K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Kirkeveien 166, 0450 Oslo, Norway.
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authors.affiliation: Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital, Aapistie 5A, FI-90220 Oulu, Finland.
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authors.affiliation: Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital, Aapistie 5A, FI-90220 Oulu, Finland.
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authors.affiliation: Human Genetics, Genome Institute of Singapore, 60 Biopolis Street 02-01, Singapore 138672, Singapore.
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authors.affiliation: Molecular Genetics of Breast Cancer, DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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authors.affiliation: Taiwan Biobank, Academia Sinica, Academia Road Nankang, Taipei 115, Taiwan.
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authors.affiliation: Breast Cancer Research Unit, Faculty of Medicine, University Malaya Cancer Research Institute, University Malaya, Lembah Pantai, 59100 Kuala Lumpur, Malaysia.
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authors.affiliation: Breast Cancer Research Unit, Faculty of Medicine, University Malaya Cancer Research Institute, University Malaya, Lembah Pantai, 59100 Kuala Lumpur, Malaysia.
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authors.affiliation: Department of Preventive Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
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authors.affiliation: 1] Department of Preventive Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea [2] Department of Biomedical Sciences, Seoul National University Graduate School, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
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authors.affiliation: Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton SO16 6YD, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK.
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authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
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authors.affiliation: Human Genetics, Genome Institute of Singapore, 60 Biopolis Street 02-01, Singapore 138672, Singapore.
authors.forename: Chiea Chuen
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authors.affiliation: Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton SO16 6YD, UK.
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authors.initials: DM
authors.lastname: Eccles
authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FI-00029 Helsinki, Finland.
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authors.affiliation: 1] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK [2] Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge CB1 8RN, UK.
authors.forename: Douglas
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden.
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authors.affiliation: Human Genetics, Genome Institute of Singapore, 60 Biopolis Street 02-01, Singapore 138672, Singapore.
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authors.lastname: Liu
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden.
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden.
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authors.initials: K
authors.lastname: Czene
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004358:Drug Therapy / Q000379:methods*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers