Journal article

Evaluation of chromosome 6p22 as a breast cancer risk modifier locus in a follow-up study of BRCA2 mutation carriers

Kristen N Stevens, Xianshu Wang, Zachary Fredericksen, Vernon S Pankratz, Mark H Greene, Irene L Andrulis, Mads Thomassen, Maria Caligo, Katherine L Nathanson, Anna Jakubowska, Ana Osorio, Ute Hamann, Andrew K Godwin, Dominique Stoppa-Lyonnet, Melissa Southey, Saundra S Buys, Christian F Singer, Thomas VO Hansen, Adalgeir Arason, Kenneth Offit Show all


University of Melbourne Researchers


Awarded by Cancer Research UK

Awarded by National Institutes of Health

Awarded by NIH

Awarded by Hereditary Cancer Research Registry from the National Cancer Institute

Awarded by Mayo Clinic Breast Cancer SPORE

Awarded by Associazione Italiana per la Ricerca sul Cancro

Awarded by Grant Agency of the Czech Republic

Awarded by Fund for Scientific Research Flanders (FWO)

Awarded by Ghent University

Awarded by Ministry of Health

Awarded by Spanish Ministry of Science and Innovation

Awarded by Basque Foundation for Health Innovation and Research (BIOEF)

Awarded by Cancer Research-UK

Awarded by Dutch Cancer Society

Awarded by NWO

Awarded by Pink Ribbon Grant

Awarded by BBMRI Grant

Awarded by National Cancer Institute, National Institutes of Health

Awarded by Association for International Cancer Research

Awarded by National Cancer Institute

Awarded by GOG Tissue Bank

Awarded by Gynecologic Oncology Group Statistical and Data Center

Awarded by Russian Foundation for Basic Research

Awarded by Commission of the European Communities

Awarded by Royal Society International Joint Grant

Awarded by Latvian Science Council Grant

Awarded by German Cancer Aid

Awarded by Helsinki University Central Hospital Research Fund, Academy of Finland

Awarded by Canadian Breast Cancer Research Alliance

Awarded by NHMRC

Awarded by Cancer Australia



Awarded by The Francis Crick Institute

Funding Acknowledgements

This study, by the Consortium of Investigators of Modifiers of BRCA1/2, was supported by grants from Cancer Research UK and by National Institutes of Health Grant CA128978, the Komen Foundation for the Cure and the Breast Cancer Research Foundation and by grants from Cancer Research UK (C12292/A11174 and C1287/A10118). All study-specific grants are: Cancer Research UK provided financial support for this work. A. C. A. is a Senior Cancer Research UK Cancer Research Fellow. D. F. E. is Cancer Research UK Principal Research Fellow. S.L.N., the Morris and Horowitz Families Endowed Professor, and Y.C.D. were supported by NIH CA74415. The MAGIC study is supported by NIH Grants R01-CA083855 and R01-CA9677. City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J.N. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The Mayo Clinic study was supported in part by the Breast Cancer Research Foundation (BCRF), a grant from Susan G. Komen for the Cure, the Mayo Clinic Breast Cancer SPORE (P50-CA116201), and NIH Grants CA122340 and CA128978 to F.J.C. KNS is a Mayo Cancer Genetic Epidemiology Training Program (CA92049-09) fellow. The Italian study (CONsorzio Studi Italiani Tumori Ereditari Alla Mammella, CONSIT TEAM) is funded in part by grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"), Associazione Italiana per la Ricerca sul Cancro (8713), Italian Ministry of Health (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro" and "Progetto Tumori Femminili"), Italian Ministry of Education, University and Research (Prin 2008) and by funds from Italian citizens who allocated the 5 9 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). CONSIT TEAM acknowledges Daniela Zaffaroni of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Bernardo Bonanni and Monica Barile of the Istituto Europeo di Oncologia, Milan, Italy; Riccardo Dolcetti of the Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy; Liliana Varesco of the AOU San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Laura Ottini of the University "La Sapienza," Rome, Italy; Laura Papi of the University of Florence, Florence, Italy; and the personnel of the Cogentech, Cancer Genetic Test Laboratory, Milan, Italy. C. I. S. is supported by the Mayo Rochester Early Career Development Award for Non-Clinician Scientists. We acknowledge the contributions of Petr Pohlreich and Zdenek Kleibl (Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic) and the support of the Grant Agency of the Czech Republic, project No. GP301/08/P103 (to M.Z.). We acknowledge the contribution of Kim De Leeneer and Anne De Paepe. This research was supported by Grant from the Fund for Scientific Research Flanders (FWO) to Kathleen Claes and by Grant 12051203 from the Ghent University to Anne De Paepe. Bruce Poppe is Senior Clinical Investigator of the Fund for Scientific Research of Flanders (FWO-Vlaanderen). Kim De Leeneer is supported by the Vlaamse Liga tegen Kanker through a grant of the Foundation Emmanuel van der Schueren. L. F., Machackova Eva, and Lukesova Miroslava's are supported through the Ministry of Health Grant CR-MZ0 MOU 2005. The research of P. L. Mai and M. H.Greene was supported by the Intramural Research Program of the US National Cancer Institute, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. Genotyping of NCI DNA samples was performed by NCI's Core Genotyping Facility, Gaithersburg, MD. We thank the investigators of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). Ontario Cancer Genetics Network (OCGN) thanks Mona Gill, Lucine Collins, Nalan Gokgoz, Teresa Selander, Nayana Weerasooriya, and members of the Ontario Cancer Genetics Network for their contributions to the study. The SMC study was supported in part by the Israel Cancer Association (ICA). SWE-BRCA acknowledge collaborators Per Karlsson, Margareta Nordling, Annika Bergman, and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Sigrun Liedgren, Linkoping University Hospital; Niklas Loman, Ha kan Olsson, Ulf Kristoffersson, Helena Jernstrom, Katja Harbst, and Karin Henriksson, Lund University Hospital; Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, and Gisela Barbany-Bustinza, Stockholm, Karolinska University Hospital; Henrik Gro nberg, Eva-Lena Stattin, and Monica Emanuelsson, Umea University Hospital; Hans Ehrencrona, Richard Rosenquist Brandell, and Niklas Dahl, Uppsala University Hospital. University of Pennsylvania (UPENN) was supported by Breast Cancer Research Foundation (to K. L. N.); Cancer Genetics Network (to S. M. D.), Marjorie Cohen Foundation (to S. M. D.). IHCC was supported by Grant PBZ_ KBN_122/P05/2004. Spanish National Cancer Center (CNIO) thanks R. M. Alonso, G Pita, and R. M. Milne for their assistance. This study was partially supported by Fundacion Mutua Madrilena, Asociacion Espanola Contra el Cancer, and the Spanish Ministry of Science and Innovation (FIS PI08 1120). Funded in part by the Basque Foundation for Health Innovation and Research (BIOEF): BIO07/CA/006. The DKFZ study was supported by the DKFZ. Douglas F. Easton is the PI of the EMBRACE study and acknowledges collaborators: North of Scotland Regional Genetics Service, Aberdeen: Helen Gregory, Zosia Miedzybrodzka. West Midlands Regional Clinical Genetics Service, Birmingham: Carole McKeown, Laura Boyes. South West Regional Genetics Service, Bristol: Alan Donaldson. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark Rogers, Emma McCann. St James's Hospital, Dublin & National Center for Medical Genetics, Dublin: David Barton. Peninsula Clinical Genetics Service. Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of Scotland Regional Genetics Service, Glasgow: Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Chris Jacobs, Caroline Langman. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Carol Chu, Tim Bishop, Julie Miller. Merseyside & Cheshire Clinical Genetics Service, Liverpool: Ian Ellis. Manchester Regional Genetics Service, Manchester: Felicity Holt. North East Thames Regional Genetics Service, NE Thames: Alison Male, Lucy Side, Anne Robinson. Nottingham Center for Medical Genetics, Nottingham: Carol Gardiner. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber. Oxford Regional Genetics Service, Oxford: Diane McLeod, Dorothy Halliday, Sarah Durrell, Barbara Stayner.The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical Genetics Service. Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. D. F. E., S. P., M. C., D. F. and C. O. are funded by Cancer Research-UK Grants C1287/A10118 and C1287/A8874. D. C. is supported by Cancer Research-UK Grant C8197/A10123. HEBON stands for The Hereditary Breast and Ovarian Cancer Research Group Netherlands and consists of the following Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M. A. Rookus, F. B. L. Hogervorst, F. E. van Leeuwen, S. Verhoef, M. K. Schmidt, J. L. de Lange; Erasmus Medical Center, Rotterdam, NL: J. M. Collee, A. M. W. van den Ouweland, M. J. Hooning, C. Seynaeve, C. H. M. van Deurzen; Leiden University Medical Center, NL: C. J. van Asperen, J. T. Wijnen, R. A. Tollenaar, P. Devilee, T. C. T. E. F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C. M. Kets, A. R. Mensenkamp; University Medical Center Utrecht, NL: M. G. E. M. Ausems, R. B. van der Luijt; Amsterdam Medical Center, NL: C. M. Aalfs, T. A. M. van Os; VU University Medical Center, Amsterdam, NL: J. J. P. Gille, Q. Waisfisz, H. E. J. Meijers-Heijboer; University Hospital Maastricht, NL: E. B. Gomez-Garcia, M. J. Blok; University Medical Center Groningen, NL: J. C. Oosterwijk, A. H. van der Hout, M. J. Mourits, G. H. de Bock. The Netherlands Foundation for the detection of hereditary tumour, Leiden, NL: H. F. Vasen. The HEBON study is supported by the Dutch Cancer Society Grants NKI19981854, NKI2004-3088, NKI2007-3756, the NWO Grant 91109024, the Pink Ribbon Grant 110005 and the BBMRI Grant CP46/NWO. The Breast Cancer Family Registry (BCFR) was supported by the National Cancer Institute, National Institutes of Health under RFACA-06-503 and through cooperative agreements with members of the BCFR and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Cancer Prevention Institute of California (U01 CA69417), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). Samples from the CPIC, FCCC, HCI, and 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 U. S. Government or the BCFR. The GEMO study is supported by the Ligue National Contre le Cancer, Association for International Cancer Research Grant AICR-07-0454, and the Association "Le cancer du sein, parlons-en!" Award. We wish to thank all the GEMO collaborating groups for their contribution to this study.GEMO Collaborating Centers are: Coordinating Centres, Unite Mixte de Genetique Constitutionnelle des Cancers Frequents, Centre Hospitalier Universitaire de Lyon/Centre Leon Berard, and UMR5201 CNRS, Universite de Lyon, Lyon: Laure Barjhoux, Sophie Giraud, Melanie Leone, Sylvie; and INSERM U509, Service de Genetique Oncologique, Institut Curie, Paris: Marion Gauthier-Villars, Claude Houdayer, Virginie Moncoutier, Muriel Belotti. Institut Gustave Roussy, Villejuif: Brigitte Bressacde-Paillerets, Audrey Remenieras, Veronique Byrde, Olivier Caron, Gilbert Lenoir. Centre Jean Perrin, Clermont-Ferrand:Yves-Jean Bignon, Nancy Uhrhammer. Institut Paoli Calmettes, Marseille: Violaine Bourdon, Francois Eisinger. Groupe Hospitalier Pitie ' -Salpetriere, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier. CHU de Arnaud-de-Villeneuve, Montpellier: Isabelle Coupier. Centre Oscar Lambret, Lille: Jean-Philippe Peyrat, Joe " lle Fournier, Franc, oise Re ' villion, Philippe Vennin, Claude Adenis. Centre Rene ' Huguenin, St Cloud: Etienne Rouleau, Rosette Lidereau, Liliane Demange. Centre Paul Strauss, Strasbourg: Danie le Muller, Jean-Pierre Fricker. Institut Bergonie ', Bordeaux: Michel Longy, Nicolas Sevenet. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU de Grenoble: Christine Rebischung. CHU de Dijon: Cecile Cassini. CHU de St-Etienne: Fabienne Prieur. Hotel Dieu Centre Hospitalier, Chambery: Sandra Fert Ferrer. CBCS thanks Mette K. Andersen and Susanne Kjaergaard for clinical data. The work was supported by the Neye Foundation. GOG was supported by National Cancer Institute grants of the Gynecologic Oncology Group Administrative Office (CA 27469), the GOG Tissue Bank (CA 27469), and the Gynecologic Oncology Group Statistical and Data Center (CA 37517 and CA 101165). GOG's participation was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program-COPTRG) NCI programs. Genotyping of GOG DNA samples was performed by NCI's Core Genotyping Facility. The technical expertise of Tim Sheehy and Amy Hutchinson is gratefully acknowledged. OSU CCG was funded by the OSU Comprehensive Cancer Center. We thank Kevin Sweet and Caroline Craven for patient accrual and data management, the Human Genetics Sample Bank for sample preparation, and the OSU Nucleic Acids Shared Resource for plate reads. IOVHBOCS was supported by the Ministero dell'Universita e della Ricerca, Ministero della Salute, and Alleanza Contro il Cancro. N. N. Petrov Institute of Oncology (NNPIO) was supported by the Russian Foundation for Basic Research (Grants 08-04-00369-a, 09-04-90402, and 10-04-92110-a), the Commission of the European Communities (Grant PITN-GA-2009-238132), and through a Royal Society International Joint Grant (JP090615). BFBOCC was supported by Latvian Science Council Grant Nr. 10.0010.08. BFBOCC also acknowledges the Genome Database of Latvian Population, Latvian Biomedical Research and Study Centre for providing data and DNA samples for BFBOCC (L. V.), and Ramunas Janavicius (Vilnius University Hospital Santariskiu Clinics, Lithuania) for data and DNA samples for BFBOCC (L. T.). UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Carole Pye and Patricia Harrington for family recruitment and technical support. We would like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry.GRFOCR qould like to acknowledge Kirsten Moysich (Department of Cancer Prevention and Control) and Kunle Odunsi (Departments Gynecologic Oncology and Immunology). WCRI was supported by the American Cancer Society Early Detection Professorship and Entertainment Industry Foundation. GC-HBOC is supported by a grant of the German Cancer Aid (Grant 107054). We thank Juliane Kohler for her excellent technical assistance, Ellen Kirsch, Isabell Eisenhauer, Hans-Jorg Plendl, Thomas Neumann, Ulrike SiebersRehnelt, Doris Steinemann, Britta Skawran, Patricia Steiner, and the 12 centers of the GC-HBOC for providing samples and clinical data. HEBCS thanks Tuomas Heikkinen and Dr. Carl Blomqvist for their help with the patient data and samples. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation. Trinidad Caldes and Miguel de la Hoya were supported by FIS 09/00859 and RD06/0020/ 0021 (RTICC; ISCIII) Spanish Ministry of Science and Innovation. Dumont, Martine Tranchant for sample management and skillful technical assistance. Jacques Simard-J. S. is Chairholder of the Canada Research Chair in Oncogenetics. This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer'' program and by the Canadian Breast Cancer Research Alliance-Grant # 019511. kConFab thanks Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC Grants 145684, 288704, and 454508 and currently by the National Breast Cancer Foundation and Cancer Australia # 628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia, Amanda Spurdle is supported by an NHMRC Senior Research Fellowship, and Georgia Chenevix-Trench by an NHMRC Senior Principal Research Fellowship. ILUH was funded by the Landspitali University Hospital Research Fund and by the Icelandic association: "Walking for Breast Cancer Research". MSKCC acknowledges support of the Sandra Taub Research Fund of the BCRF.