Common germline polymorphisms associated with breast cancer-specific survival

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.

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Item Type:	Article
Authors/Creators:	Pirie, A. Guo, Q. Kraft, P. Canisius, S. Eccles, D.M. Rahman, N. Nevanlinna, H. Chen, C. Khan, S. Tyrer, J. Bolla, M.K. Wang, Q. Dennis, J. Michailidou, K. Lush, M. Dunning, A.M. Shah, M. Czene, K. Darabi, H. Eriksson, M. Lambrechts, D. Weltens, C. Leunen, K. van Ongeval, C. Nordestgaard, B.G. Nielsen, S.F. Flyger, H. Rudolph, A. Seibold, P. Flesch-Janys, D. Blomqvist, C. Aittomaki, K. Fagerholm, R. Muranen, T.A. Olsen, J.E. Hallberg, E. Vachon, C. Knight, J.A. Glendon, G. Mulligan, A.M. Broeks, A. Cornelissen, S. Haiman, C.A. Henderson, B.E. Schumacher, F. Le Marchand, L. Hopper, J.L. Tsimiklis, H. Apicella, C. Southey, M.C. Cross, S.S. https://orcid.org/0000-0003-2044-1754 Reed, M.W.R. Giles, G.G. Milne, R.L. McLean, C. Winqvist, R. Pylkas, K. Jukkola-Vuorinen, A. Grip, M. Hooning, M.J. Hollestelle, A. Martens, J.W.M. van den Ouweland, A.M.W. Marme, F. Schneeweiss, A. Yang, R. Burwinkel, B. Figueroa, J. Chanock, S.J. Lissowska, J. Sawyer, E.J. Tomlinson, I. Kerin, M.J. Miller, N. Brenner, H. Butterbach, K. Holleczek, B. Kataja, V. Kosma, V-M. Hartikainen, J.M. Li, J. Brand, J.S. Humphreys, K. Devilee, P. Tollenaar, R.A.E.M. Seynaeve, C. Radice, P. Peterlongo, P. Manoukian, S. Ficarazzi, F. Beckmann, M.W. Hein, A. Ekici, A.B. Balleine, R. Phillips, K-A. Benitez, J. Zamora, M.P. Perez, J.I.A. Menendez, P. Jakubowska, A. Lubinski, J. Gronwald, J. Durda, K. Hamann, U. Kabisch, M. Ulmer, H.U. Ruediger, T. Margolin, S. Kristensen, V. Nord, S. Evans, D.G. Abraham, J. Earl, H. Poole, C.J. Hiller, L. Dunn, J.A. Bowden, S. Yang, R. Campa, D. Diver, W.R. Gapstur, S.M. Gaudet, M.M. Hankinson, S. Hoover, R.N. Husing, A. Kaaks, R. Machiela, M.J. Willett, W. Barrdahl, M. Canzian, F. Chin, S-F. Caldas, C. Hunter, D.J. Lindstrom, S. Garcia-Closas, M. Couch, F.J. Investigators, kConFab Chenevix-Trench, G. Mannermaa, A. Andrulis, I.L. Hall, P. Chang-Claude, J. Easton, D.F. Bojesen, S.E. Cox, A. https://orcid.org/0000-0002-5138-1099 Fasching, P.A. Pharoah, P.D.P. Schmidt, M.K. Investigators, NBCS
Copyright, Publisher and Additional Information:	© 2015 Pirie et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Dates:	Published: 22 April 2015 Accepted: 10 April 2015
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals
Depositing User:	Symplectic Sheffield
Date Deposited:	14 Apr 2016 08:29
Last Modified:	14 Apr 2016 08:29
Published Version:	http://dx.doi.org/10.1186/s13058-015-0570-7
Status:	Published
Publisher:	BioMed Central
Refereed:	Yes
Identification Number:	10.1186/s13058-015-0570-7
Related URLs:	Author
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:97451

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Common germline polymorphisms associated with breast cancer-specific survival

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