2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Jingmei Li, Linda S. Lindström, Jia N. Foo, Sajjad Rafiq, Marjanka K. Schmidt, Paul D. P. Pharoah, Kyriaki Michailidou, Joe Dennis, Manjeet K. Bolla, Qin Wang, Laura J. Van ‘t Veer, Sten Cornelissen, Emiel Rutgers, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Peter A. Fasching, Lothar Haeberle, Arif B. Ekici, Matthias W. Beckmann, Carl Blomqvist, Taru A. Muranen, Kristiina Aittomäki, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Jaana M. Hartikainen, Vesa Kataja, Georgia Chenevix-Trench, kConFab Investigators, Kelly-Anne Phillips, Sue-Anne McLachlan, Diether Lambrechts, Bernard Thienpont, Ann Smeets, Hans Wildiers, Jenny Chang-Claude, Dieter Flesch-Janys, Petra Seibold, Anja Rudolph, Graham G. Giles, Laura Baglietto, Gianluca Severi, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Vessela Kristensen, Grethe I. Grenaker Alnæs, Anne-Lise Borresen-Dale, Silje Nord, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert Tollenaar, Caroline Seynaeve, Maartje Hooning, Mieke Kriege, Antoinette Hollestelle, Ans van den Ouweland, Yi Li, Ute Hamann, Diana Torres, Hans U. Ulmer, Thomas Rüdiger, Chen-Yang Shen, Chia-Ni Hsiung, Pei-Ei Wu, Shou-Tung Chen, Soo Hwang Teo, Nur Aishah Mohd Taib, Cheng Har Yip, Gwo Fuang Ho, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Daehee Kang, Ji-Yeob Choi, Sue K. Park, Keun-Young Yoo, Tom Maishman, William J. Tapper, Alison Dunning, Mitul Shah, Robert Luben, Judith Brown, Chiea Chuen Khor, Diana M. Eccles, Heli Nevanlinna, Douglas Easton, Keith Humphreys, Jianjun Liu, Per Hall and Kamila Czene ()
Additional contact information
Jingmei Li: Human Genetics, Genome Institute of Singapore
Linda S. Lindström: University of California at San Francisco (UCSF)
Jia N. Foo: Human Genetics, Genome Institute of Singapore
Sajjad Rafiq: Faculty of Medicine, University of Southampton, University Hospital Southampton
Marjanka K. Schmidt: Netherlands Cancer Institute
Paul D. P. Pharoah: Centre for Cancer Genetic Epidemiology, University of Cambridge
Kyriaki Michailidou: Centre for Cancer Genetic Epidemiology, University of Cambridge
Joe Dennis: Centre for Cancer Genetic Epidemiology, University of Cambridge
Manjeet K. Bolla: Centre for Cancer Genetic Epidemiology, University of Cambridge
Qin Wang: Centre for Cancer Genetic Epidemiology, University of Cambridge
Laura J. Van ‘t Veer: Netherlands Cancer Institute
Sten Cornelissen: Netherlands Cancer Institute
Emiel Rutgers: Netherlands Cancer Institute
Melissa C. Southey: Genetic Epidemiology Laboratory, The University of Melbourne
Carmel Apicella: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
Gillian S. Dite: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
John L. Hopper: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
Peter A. Fasching: University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen–Nuremberg
Lothar Haeberle: University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen–Nuremberg
Arif B. Ekici: Institute of Human Genetics, Friedrich Alexander University Erlangen-Nuremberg
Matthias W. Beckmann: University Breast Center Franconia, University Hospital Erlangen, Friedrich-Alexander University Erlangen–Nuremberg
Carl Blomqvist: University of Helsinki and Helsinki University Central Hospital
Taru A. Muranen: University of Helsinki and Helsinki University Central Hospital
Kristiina Aittomäki: University of Helsinki and Helsinki University Central Hospital
Annika Lindblom: Karolinska Institutet
Sara Margolin: Karolinska Institutet
Arto Mannermaa: School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland
Veli-Matti Kosma: School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland
Jaana M. Hartikainen: School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland
Vesa Kataja: School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland
Georgia Chenevix-Trench: QIMR Berghofer Medical Research Institute
kConFab Investigators: Peter MacCallum Cancer Center
Kelly-Anne Phillips: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
Sue-Anne McLachlan: St Vincent’s Hospital Melbourne
Diether Lambrechts: Vesalius Research Center (VRC), VIB
Bernard Thienpont: Vesalius Research Center (VRC), VIB
Ann Smeets: Multidisciplinary Breast Center, University Hospitals Leuven
Hans Wildiers: Multidisciplinary Breast Center, University Hospitals Leuven
Jenny Chang-Claude: German Cancer Research Center (DKFZ)
Dieter Flesch-Janys: German Cancer Research Center (DKFZ)
Petra Seibold: German Cancer Research Center (DKFZ)
Anja Rudolph: German Cancer Research Center (DKFZ)
Graham G. Giles: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
Laura Baglietto: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
Gianluca Severi: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne
Christopher A. Haiman: Keck School of Medicine, University of Southern California
Brian E. Henderson: University of Hawaii Cancer Center
Fredrick Schumacher: Keck School of Medicine, University of Southern California
Loic Le Marchand: University of Hawaii Cancer Center
Vessela Kristensen: Institute for Cancer Research, Oslo University Hospital
Grethe I. Grenaker Alnæs: Institute for Cancer Research, Oslo University Hospital
Anne-Lise Borresen-Dale: Institute for Cancer Research, Oslo University Hospital
Silje Nord: Institute for Cancer Research, Oslo University Hospital
Robert Winqvist: Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu University Hospital
Katri Pylkäs: Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu University Hospital
Arja Jukkola-Vuorinen: Laboratory of Oncology, Oulu University Hospital, University of Oulu
Mervi Grip: Laboratory of Oncology, Oulu University Hospital, University of Oulu
Irene L. Andrulis: Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
Julia A. Knight: Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
Gord Glendon: Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
Sandrine Tchatchou: Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
Peter Devilee: Leiden University Medical Center
Robert Tollenaar: Leiden University Medical Center
Caroline Seynaeve: Erasmus MC Cancer Institute
Maartje Hooning: Erasmus MC Cancer Institute
Mieke Kriege: Erasmus MC Cancer Institute
Antoinette Hollestelle: Erasmus MC Cancer Institute
Ans van den Ouweland: Erasmus University Medical Center
Yi Li: Human Genetics, Genome Institute of Singapore
Ute Hamann: Molecular Genetics of Breast Cancer, DKFZ
Diana Torres: Molecular Genetics of Breast Cancer, DKFZ
Hans U. Ulmer: Frauenklinik der Stadtklinik Baden-Baden
Thomas Rüdiger: Institute of Pathology, Städtisches Klinikum Karlsruhe
Chen-Yang Shen: Institute of Biomedical Sciences, Academia Sinica
Chia-Ni Hsiung: Institute of Biomedical Sciences, Academia Sinica
Pei-Ei Wu: Taiwan Biobank, Academia Sinica
Shou-Tung Chen: Changhua Christian Hospital
Soo Hwang Teo: Cancer Research Initiatives Foundation, Sime Darby Medical Centre
Nur Aishah Mohd Taib: Breast Cancer Research Unit, Faculty of Medicine, University Malaya Cancer Research Institute, University Malaya
Cheng Har Yip: Breast Cancer Research Unit, Faculty of Medicine, University Malaya Cancer Research Institute, University Malaya
Gwo Fuang Ho: Faculty of Medicine, University Malaya
Keitaro Matsuo: Faculty of Medical Sciences, Kyushu University
Hidemi Ito: Aichi Cancer Center Research Institute
Hiroji Iwata: Aichi Cancer Center Hospital
Kazuo Tajima: Aichi Cancer Center Research Institute
Daehee Kang: Seoul National University College of Medicine
Ji-Yeob Choi: Seoul National University Graduate School
Sue K. Park: Seoul National University College of Medicine
Keun-Young Yoo: Seoul National University College of Medicine
Tom Maishman: Faculty of Medicine, University of Southampton, University Hospital Southampton
William J. Tapper: Faculty of Medicine, University of Southampton, University Hospital Southampton
Alison Dunning: Centre for Cancer Genetic Epidemiology, University of Cambridge
Mitul Shah: Centre for Cancer Genetic Epidemiology, University of Cambridge
Robert Luben: Centre for Cancer Genetic Epidemiology, University of Cambridge
Judith Brown: Centre for Cancer Genetic Epidemiology, University of Cambridge
Chiea Chuen Khor: Human Genetics, Genome Institute of Singapore
Diana M. Eccles: Faculty of Medicine, University of Southampton, University Hospital Southampton
Heli Nevanlinna: University of Helsinki and Helsinki University Central Hospital
Douglas Easton: Centre for Cancer Genetic Epidemiology, University of Cambridge
Keith Humphreys: Karolinska Institutet
Jianjun Liu: Human Genetics, Genome Institute of Singapore
Per Hall: Karolinska Institutet
Kamila Czene: Karolinska Institutet

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5051

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