Common germline polymorphisms associated with breast cancer-specific survival.

Ailith Pirie, Qi Guo, Peter Kraft, Sander Canisius, Diana M Eccles, Nazneen Rahman, Heli Nevanlinna, Constance Chen, Sofia Khan, Jonathan Tyrer, Manjeet K Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Michael Lush, Alison M Dunning, Mitul Shah, Kamila Czene, Hatef Darabi, Mikael Eriksson, Dieter Lambrechts, Caroline Weltens, Karin Leunen, Chantal van Ongeval, Børge G Nordestgaard, Sune F Nielsen, Henrik Flyger, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Carl Blomqvist, Kristiina Aittomäki, Rainer Fagerholm, Taru A Muranen, Janet E Olsen, Emily Hallberg, Celine Vachon, Julia A Knight, Gord Glendon, Anna Marie Mulligan, Annegien Broeks, Sten Cornelissen, Christopher A Haiman, Brian E Henderson, Frederick Schumacher, Loic Le Marchand, John L Hopper, Helen Tsimiklis, Carmel Apicella, Melissa C Southey, Simon S Cross, Malcolm Wr Reed, Graham G Giles, Roger L Milne, Catriona McLean, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Maartje J Hooning, Antoinette Hollestelle, John Wm Martens, Ans Mw van den Ouweland, Federick Marme, Andreas Schneeweiss, Rongxi Yang, Barbara Burwinkel, Jonine Figueroa, Stephen J Chanock, Jolanta Lissowska, Elinor J Sawyer, Ian Tomlinson, Michael J Kerin, Nicola Miller, Hermann Brenner, Katja Butterbach, Bernd Holleczek, Vesa Kataja, Veli-Matti Kosma, Jaana M Hartikainen, Jingmei Li, Judith S Brand, Keith Humphreys, Peter Devilee, Robert Aem Tollenaar, Caroline Seynaeve, Paolo Radice, Paolo Peterlongo, Siranoush Manoukian, Filomena Ficarazzi, Matthias W Beckmann, Alexander Hein, Arif B Ekici, Rosemary Balleine, Kelly-Anne Phillips, Javier Benitez, M Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Anna Jakubowska, Jan Lubinski, Jacek Gronwald, Katarzyna Durda, Ute Hamann, Maria Kabisch, Hans Ulrich Ulmer, Thomas Rüdiger, Sara Margolin, Vessela Kristensen, Siljie Nord, D Gareth Evans, Jean Abraham, Helena Earl, Christopher J Poole, Louise Hiller, Janet A Dunn, Sarah Bowden, Rose Yang, Daniele Campa, W Ryan Diver, Susan M Gapstur, Mia M Gaudet, Susan Hankinson, Robert N Hoover, Anika Hüsing, Rudolf Kaaks, Mitchell J Machiela, Walter Willett, Myrto Barrdahl, Federico Canzian, Suet-Feung Chin, Carlos Caldas, David J Hunter, Sara Lindstrom, Montserrat Garcia-Closas, Fergus J Couch, Georgia Chenevix-Trench, Arto Mannermaa, Irene L Andrulis, Per Hall, Jenny Chang-Claude, Douglas F Easton, Stig E Bojesen, Angela Cox, Peter A Fasching, Paul Dp Pharoah, Marjanka K Schmidt

Journal: Breast cancer research : BCR 2016;17(1):58

PMID: 25897948

Abstract

INTRODUCTION

Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.

METHODS

A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.

RESULTS

Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.

CONCLUSIONS

Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.

Address: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. [email protected].; Faculty of Medicine, University of Southampton, Highfield Campus, Southampton, SO17 1BJ, UK. [email protected].; Division of Genetics and Epidemiology, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, Surrey, UK. [email protected].; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FIN-00029 HUS, Helsinki, Finland. [email protected].; Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, FIN-00029 HUS, Helsinki, Finland. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm, 17177, Sweden. [email protected].; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm, 17177, Sweden. [email protected].; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm, 17177, Sweden. [email protected].; Vesalius Research Center (VRC), Vib, Herestraat 49, 3000, Leuven, Belgium. [email protected].; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Herestraat 49, 3000, Leuven, Belgium. [email protected].; Oncology Department, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. [email protected].; Oncology Department, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. [email protected].; Oncology Department, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium. [email protected].; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Copenhagen, Denmark. [email protected].; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Copenhagen, Denmark. [email protected].; Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2220, Copenhagen, Denmark. [email protected].; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Copenhagen, Denmark. 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[email protected].; CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. [email protected].; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, The University of Melbourne, 207 Bouverie Street, Melbourne, VIC, 3010, Australia. [email protected].; Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia. [email protected].; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, Melbourne School of Population Health, The University of Melbourne, 207 Bouverie Street, Melbourne, VIC, 3010, Australia. [email protected].; Cancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia. [email protected].; Anatomical Pathology, The Alfred Hospital, Commercial Road, Melbourne, VIC, 3007, Australia. 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[email protected].; Department of Medical Oncology, Family Cancer Clinic, Erasmus McCancer Institute, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. [email protected].; Department of Medical Oncology, Family Cancer Clinic, Erasmus McCancer Institute, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. [email protected].; Department of Obstetrics and Gynecology, University of Heidelberg, Voßstrasse 9, 69115, Heidelberg, Germany. [email protected].; National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. [email protected].; Department of Obstetrics and Gynecology, University of Heidelberg, Voßstrasse 9, 69115, Heidelberg, Germany. [email protected].; National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. [email protected].; Department of Obstetrics and Gynecology, University of Heidelberg, Voßstrasse 9, 69115, Heidelberg, Germany. [email protected].; Department of Obstetrics and Gynecology, University of Heidelberg, Voßstrasse 9, 69115, Heidelberg, Germany. [email protected].; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. [email protected].; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. [email protected].; Core Genotyping Facility, Frederick National Laboratory for Cancer Research, 8717 Grovemont Circle, Gaithersburg, MD, 20877, USA. [email protected].; Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentena 5, 02-781, Warsaw, Poland. 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[email protected].; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Frauenklinik der Stadtklinik Baden-Baden, Balger Strasse 50, 76532, Baden-Baden, Germany. [email protected].; Institute of Pathology, Städtisches Klinikum Karlsruhe, Moltkestrasse 90, 76133, Karlsruhe, Germany. [email protected].; Department of Oncology - Pathology, Karolinska Institutet, Tomtebodavägen 23b, Stockholm, 171 65, Sweden. [email protected].; Faculty of Medicine (Faculty Division Ahus), University of Oslo (UiO), Problemveien 7, Oslo, 0313, Norway. [email protected].; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Montebello, 0379, Oslo, Norway. [email protected].; Faculty of Medicine (Faculty Division Ahus), University of Oslo (UiO), Problemveien 7, Oslo, 0313, Norway. [email protected].; Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Radiumhospitalet, Montebello, 0379, Oslo, Norway. [email protected].; Genomic Medicine, Manchester Academic Health Science Centre, University of Manchester, Central Manchester Foundation Trust, St. Mary's Hospital, Oxford Road, Manchester, M13 9WL, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Cambridge Experimental Cancer Medicine Centre, Robinson Way, Cambridge, CB2 0RE, UK. [email protected].; Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, University of Cambridge NHS Foundation Hospitals, Hills Road, Cambridge, CB2 0QQ, UK. [email protected].; Cambridge Experimental Cancer Medicine Centre, Robinson Way, Cambridge, CB2 0RE, UK. [email protected].; Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, University of Cambridge NHS Foundation Hospitals, Hills Road, Cambridge, CB2 0QQ, UK. [email protected].; Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK. [email protected].; Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK. [email protected].; Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK. [email protected].; Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, the University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, UK. [email protected].; Early Detection Research Group, Division of Cancer Prevention National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892, USA. [email protected].; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Department of Biology, University of Pisa, Lungarno Pacinotti 43, 56126, Pisa, Italy. [email protected].; Epidemiology Research Program, American Cancer Society, 250 Williams Street, Atlanta, GA, 30303, USA. [email protected].; Epidemiology Research Program, American Cancer Society, 250 Williams Street, Atlanta, GA, 30303, USA. [email protected].; Epidemiology Research Program, American Cancer Society, 250 Williams Street, Atlanta, GA, 30303, USA. [email protected].; Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Division of Biostatistics and Epidemiology, University of Massachusetts-Amherst School of Public Health and Health Sciences, 715 N Pleasant Street, Amherst, MA, 01002, USA. [email protected].; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA. [email protected].; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. [email protected].; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD, 20892, USA. [email protected].; Department of Nutrition, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Breast Cancer Functional Genomics Laboratory, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, CB2 0RE, UK. [email protected].; Cambridge Experimental Cancer Medicine Centre, Robinson Way, Cambridge, CB2 0RE, UK. [email protected].; Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, University of Cambridge NHS Foundation Hospitals, Hills Road, Cambridge, CB2 0QQ, UK. [email protected].; Breast Cancer Functional Genomics Laboratory, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, CB2 0RE, UK. [email protected].; Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA. [email protected].; Division of Genetics and Epidemiology, Institute of Cancer Research, 15 Cotswold Road, Sutton, SM2 5NG, Surrey, UK. [email protected].; Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP, UK. [email protected].; Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. [email protected].; Department of Genetics, Qimr Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. [email protected].; School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine and Cancer Center of Eastern Finland, University of Eastern Finland, Yliopistonranta 1C, 70210, Kuopio, Finland. [email protected].; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Puijonlaaksontie 2, 70210, Kuopio, Finland. [email protected].; Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. [email protected].; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. [email protected].; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, Stockholm, 17177, Sweden. [email protected].; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Copenhagen, Denmark. [email protected].; Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730, Herlev, Copenhagen, Denmark. [email protected].; Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, DK-2220, Copenhagen, Denmark. [email protected].; CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. [email protected].; Institute of Human Genetics; University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-Emn, Universitaetsstrasse 21-23, 91054, Erlangen, Germany. [email protected].; David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095, USA. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, 2 Wort's Causeway, Cambridge, CB1 8RN, UK. [email protected].; Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. [email protected].
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