Journal article
Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study
A Rudolph, R Hein, S Lindström, L Beckmann, S Behrens, J Liu, H Aschard, MK Bolla, J Wang, T Truong, E Cordina-Duverger, F Menegaux, T Brüning, V Harth, WY Lo, G Severi, L Baglietto, M Southey, SJ Chanock, J Lissowska Show all
Endocrine Related Cancer | BIOSCIENTIFICA LTD | Published : 2013
DOI: 10.1530/ERC-13-0349
Abstract
Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-Analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) !3.0!10K3 were selected for replication using pooled case-control data from 11 studies..
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Grants
Awarded by European Commission
Funding Acknowledgements
Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Program under grant agreement n degrees 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692), the National Institutes of Health CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. Meetings of the BCAC have been funded by the European Union COST program (BM0606). D F Easton is a Principal Research Fellow of CR-UK. The CECILE study was funded by the Fondation de France; the French National Institute of Cancer (INCa); The National League against Cancer; the National Agency for Environmental and Occupational Health and Food Safety (ANSES), the National Agency for Research (ANR), and the Association for Research against Cancer (ARC). GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114 as well as 01KH0401, 01KH0410, 01KH0411, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center and genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). The MCBCS was supported by the NIH grants (CA122340, CA128978) and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201). MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553, and 504711 and by infrastructure provided by Cancer Council Victoria. The Nurses' Health Studies are supported by US NIH (National Institute of Health) grants CA65725, CA87969, CA49449, CA67262, CA50385, and 5UO1CA098233. OFBCR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by the NHMRC (145684, 288704, 454508). Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). ABS is supported by an NHMRC Senior Research Fellowship. The Breakthrough Generations Study investigators thank Breakthrough Breast Cancer and the Institute of Cancer Research (ICR) for support and funding of the Breakthrough Generations Study. The ICR acknowledge NHS funding to the NIHR Biomedical Research Centre.