Journal article

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

Roger L Milne, Mia M Gaudet, Amanda B Spurdle, Peter A Fasching, Fergus J Couch, Javier Benitez, Jose Ignacio Arias Perez, M Pilar Zamora, Nuria Malats, Isabel dos Santos Silva, Lorna J Gibson, Olivia Fletcher, Nichola Johnson, Hoda Anton-Culver, Argyrios Ziogas, Jonine Figueroa, Louise Brinton, Mark E Sherman, Jolanta Lissowska, John L Hopper Show all



INTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-r..

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Awarded by NHMRC

Awarded by Cancer Australia

Awarded by European Community

Awarded by Fondo de Investigacion Santiario

Awarded by National Institutes of Health, National Cancer Institute

Awarded by Lon V Smith Foundation

Awarded by United States National Cancer Institute, National Institutes of Health (NIH)

Awarded by Cancer Care Ontario

Awarded by Northern California Cancer Center

Awarded by University of Melbourne

Awarded by Federal Ministry of Education and Research (BMBF) Germany

Awarded by European Union

Awarded by Stichting tegen Kanker

Awarded by Deutsche Krebshilfe e. V.

Awarded by state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm

Awarded by U.S. Army Medical Research and Materiel Command

Awarded by NIH


Awarded by Cancer Research UK

Awarded by The Francis Crick Institute

Funding Acknowledgements

We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and members of the administrative staff who have enabled this work to be carried out. In particular, we thank: Charo Alonso, Toni Picornell, David Pisano, Eduardo Andres, Eva Barroso, Inaki De Blas Mendez and Primitiva Menendez (CNIO-BCS); Eileen Williams and Elaine Ryder-Mills (BBCS); Stephen Chanock (PBCS; National Cancer Institute, USA), Neonila Szeszenia-Dabrowska and Beata Peplonska (PBCS; Nofer Institute of Occupational Medicine, Lodz, Poland), Witold Zatonski (PBCS; M. Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland), Pei Chao and Michael Stagner (PBCS; Information Management Services, Sliver Spring MD, USA); Margaret McCredie (ABCFS); Jerry Reid (USRT; American Registry of Radiologic Technologists), Laura Bowen (USRT), Diane Kampa and Allison Iwan (USRT; University of Minnesota); Helena Kemilainen, Aija Parkkinen and Eija Myohanen (KBCP); Helen Cramp, Dan Connley, Sue Higham, Ian Brock, Saba Balasubramanian and Graeme Elliott (SBCS); Christina Justenhoven, Ute Hamann, Christian Baisch, Hans-Peter Fischer, Beate Pesch, Volker Harth and Sylvia Rabstein (GENICA); Gilian Peuteman, Dominiek Smeets, Sofie Van Soest and Kathleen Corthouts (LMBC); Ursula Eilber, Belinda Kaspereit and Tanya Koehler (GESBC); Heather Thorne, Eveline Niedermayr and the Family Cancer Clinics (kConFab), the kConFab team and the kConFab Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333); D Bowtell, G Chenevix-Trench, A deFazio, D Gertig, A Green, P Webb (AOCS Management Group); Mary Karaus, Catie Erding and Xianshu Wang (MCBCS); Tracy Slanger, Elke Mutschelknauss, S. Behrens, R. Birr, W. Busch, U. Eilber, B. Kaspereit, N. Knese, K. Smit and the pathology institutes (MARIE); the SEARCH team, Caroline Baynes, Craig Luccarini and Don Conroy (SEARCH).Part of this work was supported by the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175). The CNIO-BCS work was partly funded by the Red Tematica de Investigacion Cooperativa en Cancer, the Asociacion Espanola Contra Cancer and grants from the Fondo de Investigacion Santiario (PI081583 to RLM and PI081120 to JB). The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The UCIBCS is supported by the National Institutes of Health, National Cancer Institute grants CA-58860, CA-92044 and the Lon V Smith Foundation grant LVS-39420. The ABCFS, NC-BCFR and OFBCR work was supported by the United States National Cancer Institute, National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638). Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. 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 BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. JLH is a National Health and Medical Research Council (NHMRC) Australia Fellow and a Victorian Breast Cancer Research Consortium Group Leader. MCS is a NHMRC Senior Research Fellow and a Victorian Breast Cancer Research Consortium Group Leader. The USRT study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. The KBCP is supported by EVO funds from Kuopio University Hospital and Vaasa Central Hospital, and grants from the Academy of Finland and the Finnish Cancer Foundation. The SBCS was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. The GENICA Network was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation of Medical Research, 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 LMBC is supported by European Union Framework Programme 6 Project LSHC-CT-2003-503297 (the Cancerdegradome) and by the 'Stichting tegen Kanker' (232-2008). The GESBC was supported by the Deutsche Krebshilfe e. V. (70492), with genotyping partly funded by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P. 685).The kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Autralia, and the Cancer Foundation of Western Australia. Financial support to the AOCS was provided by the U.S. Army Medical Research and Materiel Command under DAMD17-01-1-0729, the Cancer Council Tasmania and Cancer Foundation of Western Australia. ABS and GCT are Senior and Senior Principal Research Fellows, respectively, of the NHMRC. The MCCS was funded by grants from the NHMRC (251533, 209057, 504711) and was further supported by infrastructure provided by The Cancer Council Victoria. The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Copenhagen University Hospital, Herlev Hospital. The MCBCS was supported by NIH grant CA122340 and the NIH breast cancer specialized program of research excellence (CA116201). The MARIE study was supported by the Deutsche Krebshilfe e. V., grant number 70-2892-BR I, the Hamburg Cancer Society and the German Cancer Research Center. The BBCC was partly funded by the ELAN Program of the University Hospital of Erlangen. P. A. F. was funded by the Dr. Mildred Scheel Foundation of the Deutsche Krebshilfe. SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the NIH and the Susan G. Komen Breast Cancer Foundation. The Breast Cancer Association Consortium and SEARCH are funded by grants from Cancer Research UK. DFE is a Cancer Research UK Principal Research Fellow. None of these funding bodies had any role in the analysis or interpretation of data, in the writing of the manuscript or in the decision to submit the manuscript for publication.