University of Oulu

Morra, A., Escala-Garcia, M., Beesley, J. et al. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. Breast Cancer Res 23, 86 (2021). https://doi.org/10.1186/s13058-021-01450-7

Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Saved in:
Author: Morra, Anna1; Escala-Garcia, Maria1; Beesley, Jonathan2;
Keeman, Renske1; Canisius, Sander1,3; Ahearn, Thomas U.4; Andrulis, Irene L.5,6; Anton-Culver, Hoda7; Arndt, Volker8; Auer, Paul L.9,10; Augustinsson, Annelie11; Freeman, Laura E. Beane4; Becher, Heiko12; Beckmann, Matthias W.13; Behrens, Sabine14; Bojesen, Stig E.15,16,17; Bolla, Manjeet K.18; Brenner, Hermann8,19,20,21; Bruening, Thomas22; Buys, Saundra S.23; Caan, Bette24; Campa, Daniele14,25; Canzian, Federico26; Castelao, Jose E.27; Chang-Claude, Jenny14,28; Chanock, Stephen J.4; Cheng, Ting-Yuan David29; Clarke, Christine L.30; Colonna, Sarah, V23; Couch, Fergus J.31; Cox, Angela32; Cross, Simon S.33; Czene, Kamila34; Daly, Mary B.35; Dennis, Joe18; Dork, Thilo36; Dossus, Laure37; Dunning, Alison M.38; Dwek, Miriam39; Eccles, Diana M.40; Ekici, Arif B.41; Eliassen, A. Heather42,43,44; Eriksson, Mikael34; Evans, D. Gareth45,46; Fasching, Peter A.13,47; Flyger, Henrik48; Fritschi, Lin49; Gago-Dominguez, Manuela50,51; Garcia-Saenz, Jose A.52; Giles, Graham G.53,54,55; Grip, Mervi56; Guenel, Pascal57; Guendert, Melanie58,59,60; Hahnen, Eric61,62; Haiman, Christopher A.63; Hakansson, Niclas64; Hall, Per34,65; Hamann, Ute66; Hart, Steven N.67; Hartikainen, Jaana M.68,69; Hartmann, Arndt70; He, Wei34; Hooning, Maartje J.71; Hoppe, Reiner72,73; Hopper, John L.54; Howell, Anthony74; Hunter, David J.44,75; Jager, Agnes71; Jakubowska, Anna76,77; Janni, Wolfgang78; John, Esther M.79,80; Jung, Audrey Y.14; Kaaks, Rudolf14; Keupers, Machteld81; Kitahara, Cari M.82; Koutros, Stella4; Kraft, Peter44,83; Kristensen, Vessela N.84,85,86; Kurian, Allison W.79,80; Lacey, James, V87,88; Lambrechts, Diether89,90; Le Marchand, Loic91; Lindblom, Annika92,93; Linet, Martha82; Luben, Robert N.94; Lush, Michael18; Mannermaa, Arto68,69,95; Manoochehri, Mehdi66; Margolin, Sara65,96; Martens, John W. M.71; Martinez, Maria Elena51,97; Mavroudis, Dimitrios98; Michailidou, Kyriaki18,99,100; Milne, Roger L.53,54,55; Mulligan, Anna Marie101,102; Muranen, Taru A.103; Nevanlinna, Heli103; Newman, William G.45,46; Nielsen, Sune F.15,16; Nordestgaard, Borge G.15,16,17; Olshan, Andrew F.104,105; Olsson, Hakan11; Orr, Nick106; Park-Simon, Tjoung-Won36; Patel, Alpa, V107; Peissel, Bernard108; Peterlongo, Paolo109; Plaseska-Karanfilska, Dijana110; Prajzendanc, Karolina76; Prentice, Ross9; Presneau, Nadege39; Rack, Brigitte78; Rennert, Gad111,112; Rennert, Hedy S.111,112; Rhenius, Valerie38; Romero, Atocha113; Roylance, Rebecca114; Lubinski, Jan76; Ruebner, Matthias13; Saloustros, Emmanouil115; Sawyer, Elinor J.116; Schmutzler, Rita K.61,62,117,118; Schneeweiss, Andreas59,119,120; Scott, Christopher67; Shah, Mitul38; Smichkoska, Snezhana121; Southey, Melissa C.53,55,122; Stone, Jennifer54,123; Surowy, Harald58,59; Swerdlow, Anthony J.124,125; Tamimi, Rulla M.44,126; Tapper, William J.40; Teras, Lauren R.107; Terry, Mary Beth127; Tollenaar, Rob A. E. M.128; Tomlinson, Ian129,130,131; Troester, Melissa A.104,105; Truong, Therese57; Vachon, Celine M.132; Wang, Qin18; Hurson, Amber N.4; Winqvist, Robert133,134; Wolk, Alicja64,135; Ziogas, Argyrios7; Brauch, Hiltrud72,136,137,138; Garcia-Closas, Montserrat4; Pharoah, Paul D. P.18,38; Easton, Douglas F.18,38; Chenevix-Trench, Georgia2; Schmidt, Marjanka K.1,139
Organizations: 1Antoni van Leeuwenhoek Hosp, Div Mol Pathol, Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
2QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia.
3Antoni van Leeuwenhoek Hosp, Div Mol Carcinogenesis, Netherlands Canc Inst, Amsterdam, Netherlands.
4NCI, US Dept HHS, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
5Fred A Litwin Ctr Canc Genet, Lunenfeld Tanenbaum Res Inst Mt Sinai Hosp, Toronto, ON, Canada.
6Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
7Univ Calif Irvine, Dept Med, Genet Epidemiol Res Inst, Irvine, CA 92717 USA.
8German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
9Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
10Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
11Lund Univ, Dept Canc Epidemiol, Clin Sci, Lund, Sweden.
12Univ Med Ctr Hamburg Eppendorf, Inst Med Biometry & Epidemiol, Hamburg, Germany.
13Friedrich Alexander Univ Erlangen Nuremberg FAU, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, Erlangen, Germany.
14German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
15Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
16Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark.
17Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
18Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
19German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
20Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
21German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
22Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med, German Social Accid Insurance, Bochum, Germany.
23Huntsman Canc Inst, Dept Med, Salt Lake City, UT USA.
24Kaiser Permanente, Div Res, Oakland, CA USA.
25Univ Pisa, Dept Biol, Pisa, Italy.
26German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
27Xerencia Xest Integrada Vigo SERGAS, Oncol & Genet Unit, Inst Invest Sanitaria Galicia Sur IISGS, Vigo, Spain.
28Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg UCCH, Canc Epidemiol Grp, Hamburg, Germany.
29Roswell Park Canc Inst, Div Canc Prevent & Control, Buffalo, NY 14263 USA.
30Univ Sydney, Westmead Inst Med Res, Sydney, NSW, Australia.
31Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
32Univ Sheffield, Sheffield Inst Nucle Acids SInFoNiA, Dept Oncol & Metab, Sheffield, S Yorkshire, England.
33Univ Sheffield, Acad Unit Pathol, Dept Neurosci, Sheffield, S Yorkshire, England.
34Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
35Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
36Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
37Int Agcy Res Canc IARC WHO, Nutr & Metab Sect, Lyon, France.
38Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
39Univ Westminster, Sch Life Sci, London, England.
40Univ Southampton, Fac Med, Southampton, Hants, England.
41Friedrich Alexander Univ Erlangen Nuremberg FAU, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Inst Human Genet, Erlangen, Germany.
42Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
43Harvard Med Sch, Channing Div Network Med, Boston, MA 02115 USA.
44Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
45Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Sch Biol Sci,Div Evolut & Genom Sci, Manchester, Lancs, England.
46Manchester Univ NHS Fdn Trust, St Marys Hosp, Manchester Acad Hlth Sci Ctr, North West Genom Lab Hub,Manchester Ctr Genom Med, Manchester, Lancs, England.
47Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
48Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Breast Surg, Herlev, Denmark.
49Curtin Univ, Sch Publ Hlth, Perth, WA, Australia.
50Galician Publ Fdn Genom Med FPGMX, Hlth Res Inst Santiago IDIS, Int Canc Genet & Epidemiol Grp, Genom Med Grp, Santiago De Compostela, Spain.
51Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
52Hosp Clin San Carlos, Ctr Invest Biomed Red Canc CIBERONC, Inst Invest Sanitaria San Carlos IdISSC, Med Oncol Dept, Madrid, Spain.
53Canc Council Victoria, Canc Epidemiol Div, Victoria, Australia.
54Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Victoria, Australia.
55Monash Univ, Sch Clin Sci, Precis Med, Monash Hlth, Clayton, Vic, Australia.
56Univ Oulu, Oulu Univ Hosp, Dept Surg, Oulu, Finland.
57Univ Paris Saclay, Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Team Exposome & Hered, Villejuif, France.
58German Canc Res Ctr, Mol Epidemiol Grp, C080, Heidelberg, Germany.
59Heidelberg Univ, Univ Womens Clin Heidelberg, Mol Biol Breast Canc, Heidelberg, Germany.
60Helmholtz Zentrum Munchen, Inst Diabet Res, German Res Ctr Environm Hlth, Neuherberg, Germany.
61Univ Cologne, Fac Med, Cologne, Germany.
62Univ Cologne, Univ Hosp Cologne, Ctr Integrated Oncol CIO, Cologne, Germany.
63Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
64Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
65Soder Sjukhuset, Dept Oncol, Stockholm, Sweden.
66German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
67Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
68Univ Eastern Finland, Translat Canc Res Area, Kuopio, Finland.
69Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
70Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen Nuremberg, Inst Pathol, Erlangen, Germany.
71Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands.
72Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
73Univ Tubingen, Tubingen, Germany.
74Univ Manchester, Div Canc Sci, Manchester, Lancs, England.
75Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
76Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
77Pomeranian Med Univ, Independent Lab Mol Biol & Genet Diagnost, Szczecin, Poland.
78Univ Hosp Ulm, Dept Gynaecol & Obstet, Ulm, Germany.
79Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA.
80Stanford Univ, Stanford Canc Inst, Dept Med, Div Oncol,Sch Med, Stanford, CA 94305 USA.
81Univ Leuven, Univ Hosp Leuven, Dept Radiat Oncol, Leuven, Belgium.
82NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
83Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA.
84Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.
85Oslo Univ Hosp, Dept Med Genet, Oslo, Norway.
86Univ Oslo, Oslo, Norway.
87City Hope Natl Med Ctr, Dept Computat & Quantitat Med, Duarte, CA USA.
88City Hope Natl Med Ctr, City Hope Comprehens Canc Ctr, Duarte, CA USA.
89VIB Ctr Canc Biol, Leuven, Belgium.
90Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium.
91Univ Hawaii, Canc Ctr, Epidemiol Program, Honolulu, HI 96822 USA.
92Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
93Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
94Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England.
95Kuopio Univ Hosp, Biobank Eastern Finland, Kuopio, Finland.
96Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
97Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
98Univ Hosp Heraklion, Dept Med Oncol, Iraklion, Greece.
99Cyprus Inst Neurol & Genet, Biostat Unit, Nicosia, Cyprus.
100Cyprus Sch Mol Med, Cyprus Inst Neurol & Genet, Nicosia, Cyprus.
101Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
102Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
103Univ Helsinki, Helsinki Univ Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
104Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
105Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
106Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland.
107Amer Canc Soc, Dept Populat Sci, Atlanta, GA 30329 USA.
108Fdn IRCCS Ist Nazl Tumori Milano, Dept Med Oncol & Hematol, Unit Med Genet, Milan, Italy.
109IFOM FIRC Inst Mol Oncol, Genome Diagnost Program, Milan, Italy.
110Res Ctr Genet Engn & Biotechnol Georgi D Efremov, MASA, Skopje, North Macedonia.
111Carmel Hosp, Haifa, Israel.
112Technion Fac Med, Clalit Natl Canc Control Ctr, Haifa, Israel.
113Hosp Univ Puerta de Hierro, Med Oncol Dept, Madrid, Spain.
114UCLH Fdn Trust, Dept Oncol, London, England.
115Univ Hosp Larissa, Dept Oncol, Larisa, Greece.
116Kings Coll London, Comprehens Canc Ctr, Sch Canc & Pharmaceut Sci, Guys Campus, London, England.
117Univ Cologne, Fac Med, Ctr Mol Med Cologne CMMC, Cologne, Germany.
118Univ Cologne, Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany.
119Univ Hosp, Heidelberg, Germany.
120German Canc Res Ctr, Natl Ctr Tumor Dis, Heidelberg, Germany.
121Ss Cyril & Methodius Univ Skopje, Univ Clin Radiotherapy & Oncol, Med Fac, Skopje, North Macedonia.
122Univ Melbourne, Dept Clin Pathol, Melbourne, Vic, Australia.
123Univ Western Australia, Sch Populat & Global Hlth, Genet Epidemiol Grp, Perth, WA, Australia.
124Inst Canc Res, Div Genet & Epidemiol, London, England.
125Inst Canc Res, Div Breast Canc Res, London, England.
126Weill Cornell Med, Dept Populat Hlth Sci, New York, NY USA.
127Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
128Leiden Univ Med Ctr, Dept Surg, Leiden, Netherlands.
129Univ Birmingham, Inst Canc & Genom Sci, Birmingham, W Midlands, England.
130Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
131Univ Oxford, Oxford NIHR Biomed Res Ctr, Oxford, England.
132Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
133Univ Oulu, Bioctr Oulu, Canc & Translat Med Res Unit, Lab Canc Genet & Tumor Biol, Oulu, Finland.
134Northern Finland Lab Ctr Oulu, Lab Canc Genet & Tumor Biol, Oulu, Finland.
135Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
136Univ Tubingen, iFIT Cluster Excellence, Tubingen, Germany.
137German Canc Res Ctr, Tubingen, Germany.
138German Canc Consortium DKTK, Partner Site Tubingen, Tubingen, Germany.
139Antoni van Leeuwenhoek Hosp, Div Psychosocial Res & Epidemiol, Netherlands Canc Inst, Amsterdam, Netherlands.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021121761684
Language: English
Published: Springer Nature, 2021
Publish Date: 2021-12-17
Description:

Abstract

Background: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.

Methods: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP & 0.15).

Results: Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E−08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E−07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E−08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E−08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.

Conclusions: We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.

see all

Series: Breast cancer research
ISSN: 1465-5411
ISSN-E: 1465-542X
ISSN-L: 1465-5411
Volume: 23
Issue: 1
Article number: 86
DOI: 10.1186/s13058-021-01450-7
OADOI: https://oadoi.org/10.1186/s13058-021-01450-7
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: BCAC is funded by Cancer Research UK [C1287/A16563], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.; Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer Research UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344), and the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F22009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1 U19 CA148537, 1 U19 CA148065 and 1 U19 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, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). 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 USA 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. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW, and the National Breast Cancer Foundation. The ACP study is funded by the Breast Cancer Research Trust, UK. KM and AL are supported by the NIHR Manchester Biomedical Research Centre, the Allan Turing Institute, and, by the ICEP (Cancer Research UK (C18281/A19169). The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant number Z01-CP010119), and the National Institute of Environmental Health Sciences (grant number Z01-ES049030). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia. For the BCFR-NY, BCFRPA, and BCFR-UT, this work 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 BCINIS study is supported in part by the Breast Cancer Research Foundation (BCRF).; For BIGGS, ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London, UK. IT is supported by the Oxford Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER, PI17/00918/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the DietmarHopp Foundation, the Helmholtz Society and the German Cancer Research Center CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The American Cancer Society funds the creation, maintenance, and updating of the CPS-II cohort. The California Teachers Study and the research reported in this publication were supported by the National Cancer Institute of the National Institutes of Health under award number U01-CA199277; P30-CA033572; P30-CA023100; UM1-CA164917; and R01-CA077398. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The collection of cancer incidence data used in the California Teachers Study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention's National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The opinions, findings, and conclusions expressed herein are those of the author(s) and do not necessarily reflect the official views of the State of California, Department of Public Health, the National Cancer Institute, the National Institutes of Health, the Centers for Disease Control and Prevention or their Contractors and Subcontractors, or the Regents of the University of California, or any of its programs. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN.; The coordination of EPIC is financially supported by the European Commission national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707-10031. D.G.E. is supported by the all Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE 713-241202, 713241202, 14505/2470, 14575/2470). The GENICA 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, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research. The HEBCS was financially supported by the Helsinki University Hospital Research Fund, the Finnish Cancer Society, and the Sigrid Juselius Foundation. ICICLE was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer.; The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. LMBC is supported by the 'Stichting tegen Kanker'. DL is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov," MASA. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402 and 01ER1306]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The MEC was supported by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. The NBCS has received funding from the K.G. Jebsen Centre for Breast Cancer Research; the Research Council of Norway grant 193387/V50 Borresen-Dale and V.N. Kristensen), South Eastern Norway Health Authority (grant 39346 to A-L Borresen-Dale) and the Norwegian Cancer Society (to A-L Borresen-Dale and V.N. Kristensen). The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant U01CA164920 from the USA National Cancer Institute of the National Institutes of Health.; 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 USA Government or the BCFR. The Carolina Breast Cancer Study (NCBCS) was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants U01 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital-based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707-10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore Komen Breast Cancer Foundation. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council (VR 2017-00644) grant for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER). The SZBCS was supported by Grant PBZ_KBN_122/P05/2004 and the program of the Minister of Science and Higher Education under the name "Regional Initiative of Excellence" in 2019-2022 project number 002/RID/2018/19 amount of financing 12 000 000 PLN. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research Research Centre.; The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C). This work was also funded by NCI U19 CA148065-01.
Academy of Finland Grant Number: 250083
122715
251314
Detailed Information: 250083 (Academy of Finland Funding decision)
122715 (Academy of Finland Funding decision)
251314 (Academy of Finland Funding decision)
Copyright information: The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit ttp://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
  https://creativecommons.org/licenses/by/4.0/