2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Jingmei Li; Linda S. Lindström; Jia N. Foo; Sajjad Rafiq; Marjanka K. Schmidt; Paul D.P. Pharoah; Kyriaki Michailidou; Joe Dennis; Manjeet K. Bolla; Qin Wang; Laura J. Van'T Veer; Sten Cornelissen; Emiel Rutgers; Melissa C. Southey; Carmel Apicella; Gillian S. Dite; John L. Hopper; Peter A. Fasching; Lothar Haeberle; Arif B. Ekici; Matthias W. Beckmann; Carl Blomqvist; Taru A. Muranen; Kristiina Aittomäki; Annika Lindblom; Sara Margolin; Arto Mannermaa; Veli Matti Kosma; Jaana M. Hartikainen; Vesa Kataja; Georgia Chenevix-Trench; Kconfab Investigators; Kelly Anne Phillips; Sue Anne McLachlan; Diether Lambrechts; Bernard Thienpont; Ann Smeets; Hans Wildiers; Jenny Chang-Claude; Dieter Flesch-Janys; Petra Seibold; Anja Rudolph; Graham G. Giles; Laura Baglietto; Gianluca Severi; Christopher A. Haiman; Brian E. Henderson; Fredrick Schumacher; Loic Le Marchand; Vessela Kristensen; Grethe I.Grenaker Alnæs; Anne Lise Borresen-Dale; Silje Nord; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Mervi Grip; Irene L. Andrulis; Julia A. Knight; Gord Glendon; Sandrine Tchatchou; Peter Devilee; Robert Tollenaar; Caroline Seynaeve; Maartje Hooning; Mieke Kriege; Antoinette Hollestelle; Ans Van Den Ouweland; Yi Li; Ute Hamann; Diana Torres; Hans U. Ulmer; Thomas Rüdiger; Chen Yang Shen; Chia Ni Hsiung; Pei Ei Wu; Shou Tung Chen; Soo Hwang Teo; Nur Aishah Mohd Taib; Cheng Har Yip; Gwo Fuang Ho; Keitaro Matsuo; Hidemi Ito; Hiroji Iwata; Kazuo Tajima; Daehee Kang; Ji Yeob Choi; Sue K. Park; Keun Young Yoo; Tom Maishman; William J. Tapper; Alison Dunning; Mitul Shah; Robert Luben; Judith Brown; Chiea Chuen Khor; Diana M. Eccles; Heli Nevanlinna; Douglas Easton; Keith Humphreys; Jianjun Liu; Per Hall; Kamila Czene

doi:10.1038/ncomms5051

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Jingmei Li, Linda S. Lindström, Jia N. Foo, Sajjad Rafiq, Marjanka K. Schmidt, Paul D.P. Pharoah, Kyriaki Michailidou, Joe Dennis, Manjeet K. Bolla, Qin Wang, Laura J. Van'T Veer, Sten Cornelissen, Emiel Rutgers, Melissa C. Southey, Carmel Apicella, Gillian S. Dite, John L. Hopper, Peter A. Fasching, Lothar Haeberle, Arif B. EkiciMatthias W. Beckmann, Carl Blomqvist, Taru A. Muranen, Kristiina Aittomäki, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli Matti Kosma, Jaana M. Hartikainen, Vesa Kataja, Georgia Chenevix-Trench, Kconfab Investigators, Kelly Anne Phillips, Sue Anne McLachlan, Diether Lambrechts, Bernard Thienpont, Ann Smeets, Hans Wildiers, Jenny Chang-Claude, Dieter Flesch-Janys, Petra Seibold, Anja Rudolph, Graham G. Giles, Laura Baglietto, Gianluca Severi, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Vessela Kristensen, Grethe I.Grenaker Alnæs, Anne Lise Borresen-Dale, Silje Nord, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Mervi Grip, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Sandrine Tchatchou, Peter Devilee, Robert Tollenaar, Caroline Seynaeve, Maartje Hooning, Mieke Kriege, Antoinette Hollestelle, Ans Van Den Ouweland, Yi Li, Ute Hamann, Diana Torres, Hans U. Ulmer, Thomas Rüdiger, Chen Yang Shen, Chia Ni Hsiung, Pei Ei Wu, Shou Tung Chen, Soo Hwang Teo, Nur Aishah Mohd Taib, Cheng Har Yip, Gwo Fuang Ho, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Kazuo Tajima, Daehee Kang, Ji Yeob Choi, Sue K. Park, Keun Young Yoo, Tom Maishman, William J. Tapper, Alison Dunning, Mitul Shah, Robert Luben, Judith Brown, Chiea Chuen Khor, Diana M. Eccles, Heli Nevanlinna, Douglas Easton, Keith Humphreys, Jianjun Liu, Per Hall, Kamila Czene

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16 Citas (Scopus)

Resumen

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

Idioma original	Inglés
Número de artículo	4051
Publicación	Nature Communications
Volumen	5
DOI	https://doi.org/10.1038/ncomms5051
Estado	Publicada - 17 jun. 2014

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Li, J., Lindström, L. S., Foo, J. N., Rafiq, S., Schmidt, M. K., Pharoah, P. D. P., Michailidou, K., Dennis, J., Bolla, M. K., Wang, Q., Van'T Veer, L. J., Cornelissen, S., Rutgers, E., Southey, M. C., Apicella, C., Dite, G. S., Hopper, J. L., Fasching, P. A., Haeberle, L., ... Czene, K. (2014). 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy. Nature Communications, 5, Artículo 4051. https://doi.org/10.1038/ncomms5051

@article{4b10cd45a2924b3c97304ac84ca3dde0,

title = "2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy",

abstract = "Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 {\^a}{\^ }'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.",

author = "Jingmei Li and Lindstr{\"o}m, {Linda S.} and Foo, {Jia N.} and Sajjad Rafiq and Schmidt, {Marjanka K.} and Pharoah, {Paul D.P.} and Kyriaki Michailidou and Joe Dennis and Bolla, {Manjeet K.} and Qin Wang and {Van'T Veer}, {Laura J.} and Sten Cornelissen and Emiel Rutgers and Southey, {Melissa C.} and Carmel Apicella and Dite, {Gillian S.} and Hopper, {John L.} and Fasching, {Peter A.} and Lothar Haeberle and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Carl Blomqvist and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Annika Lindblom and Sara Margolin and Arto Mannermaa and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Vesa Kataja and Georgia Chenevix-Trench and Kconfab Investigators and Phillips, {Kelly Anne} and McLachlan, {Sue Anne} and Diether Lambrechts and Bernard Thienpont and Ann Smeets and Hans Wildiers and Jenny Chang-Claude and Dieter Flesch-Janys and Petra Seibold and Anja Rudolph and Giles, {Graham G.} and Laura Baglietto and Gianluca Severi and Haiman, {Christopher A.} and Henderson, {Brian E.} and Fredrick Schumacher and {Le Marchand}, Loic and Vessela Kristensen and Aln{\ae}s, {Grethe I.Grenaker} and Borresen-Dale, {Anne Lise} and Silje Nord and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Sandrine Tchatchou and Peter Devilee and Robert Tollenaar and Caroline Seynaeve and Maartje Hooning and Mieke Kriege and Antoinette Hollestelle and {Van Den Ouweland}, Ans and Yi Li and Ute Hamann and Diana Torres and Ulmer, {Hans U.} and Thomas R{\"u}diger and Shen, {Chen Yang} and Hsiung, {Chia Ni} and Wu, {Pei Ei} and Chen, {Shou Tung} and Teo, {Soo Hwang} and Taib, {Nur Aishah Mohd} and {Har Yip}, Cheng and {Fuang Ho}, Gwo and Keitaro Matsuo and Hidemi Ito and Hiroji Iwata and Kazuo Tajima and Daehee Kang and Choi, {Ji Yeob} and Park, {Sue K.} and Yoo, {Keun Young} and Tom Maishman and Tapper, {William J.} and Alison Dunning and Mitul Shah and Robert Luben and Judith Brown and {Chuen Khor}, Chiea and Eccles, {Diana M.} and Heli Nevanlinna and Douglas Easton and Keith Humphreys and Jianjun Liu and Per Hall and Kamila Czene",

note = "Funding Information: The HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundatin and Bert von Kantzows foundation. 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, the Academy of Finland and by the strategic funding of the University of Eastern Finland. 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, Cancer Australia and the National Breast Cancer Foundation. K.A.P. is a National Breast Cancer Foundation Practitioner Fellow. L.M.B.C. is supported by the {\textquoteleft}Stichting tegen Kanker{\textquoteright} (232-2008 and 196-2010). 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 the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). 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 MEC was supported by NIH grants CA63464, CA54281, CA098758 and CA132839. The NBCS was supported by grants from the Norwegian Research council (155218/V40, 175240/S10 to A.L.B.D., FUGE-NFR 181600/V11 to V.N.K. and a Swizz Bridge Award to A.L.B.D.). The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu and the Oulu University Hospital. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). pKARMA is a combination of the KARMA and LIBRO-1 studies. KARMA was supported by M{\"a}rit and Hans Rausings Initiative Against Breast Cancer. KARMA and LIBRO-1 were supported the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linnaeus Centre (Contract ID 70867902) financed by the Swedish Research Council. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. K.C. was financed by the Swedish Cancer Society (5128-B07-01PAF). SEARCH is funded by a programme grant from Cancer Research UK (C490/ A10124) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. SKKDKFZS is supported by the DKFZ. The TWBCS is supported by the Institute of Biomedical Sciences, Academia Sinica and the National Science Council, Taiwan. MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). The HERPACC was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by a research grant from Takeda Science Foundation, by the Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by the National Cancer Center Research and Development Fund. The SEBCS was supported by the Korea Health 21 R&D Project (AO30001), Ministry of Health and Welfare, Republic of Korea. POSH was supported by Funding Breast Cancer Campaign (NOV210PR62) and Cancer Research UK (C1275/A9896). 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. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and M.C.S. is a NHMRC Senior Research Fellow. D.F.E. is a Principal Research Fellow of CR-UK.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We thank all the individuals who took part in these studies and all the researchers, study staff, clinicians and other health care providers, technicians and administrative staff who have enabled this work to be carried out. This work was financed by the Swedish Research Council (grant number: 521-2011-3187 and 524-2011-6857 to L.L.); G{\"o}sta Miltons Donationsfond to L.L., Swedish Cancer Society (grant number: CAN 2010/807 and 5128-B07-01PAF to K.C.) and a UNESCO-L{\textquoteright}Or{\'e}al International Fellowship to J.L. This study was also supported by the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linneus Centre (Contract ID 70867902) financed by the Swedish Research Council. Funding for the iCOGS infrastructure came from: the European Community{\textquoteright}s Seventh Framework Programme under grant agreement number 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. The ABCFS and OFBCR work was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The OFBCR work was also supported by the Canadian Institutes of Health Research {\textquoteleft}CIHR Team in Familial Risks of Breast Cancer{\textquoteright} programme. The ABCS was funded by Dutch Cancer Society grant numberNKI2007-3839; M.K.S. was funded by Dutch Cancer Society grant number NKI2009-4363. The work of the BBCC was partly funded by ELAN-Programme of the University Hospital of Erlangen. The BCAC is funded by CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). E.S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London, United Kingdom. I.T. is supported by the Oxford Biomedical Research Centre.",

year = "2014",

month = jun,

day = "17",

doi = "10.1038/ncomms5051",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Li, J, Lindström, LS, Foo, JN, Rafiq, S, Schmidt, MK, Pharoah, PDP, Michailidou, K, Dennis, J, Bolla, MK, Wang, Q, Van'T Veer, LJ, Cornelissen, S, Rutgers, E, Southey, MC, Apicella, C, Dite, GS, Hopper, JL, Fasching, PA, Haeberle, L, Ekici, AB, Beckmann, MW, Blomqvist, C, Muranen, TA, Aittomäki, K, Lindblom, A, Margolin, S, Mannermaa, A, Kosma, VM, Hartikainen, JM, Kataja, V, Chenevix-Trench, G, Investigators, K, Phillips, KA, McLachlan, SA, Lambrechts, D, Thienpont, B, Smeets, A, Wildiers, H, Chang-Claude, J, Flesch-Janys, D, Seibold, P, Rudolph, A, Giles, GG, Baglietto, L, Severi, G, Haiman, CA, Henderson, BE, Schumacher, F, Le Marchand, L, Kristensen, V, Alnæs, GIG, Borresen-Dale, AL, Nord, S, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Devilee, P, Tollenaar, R, Seynaeve, C, Hooning, M, Kriege, M, Hollestelle, A, Van Den Ouweland, A, Li, Y, Hamann, U, Torres, D, Ulmer, HU, Rüdiger, T, Shen, CY, Hsiung, CN, Wu, PE, Chen, ST, Teo, SH, Taib, NAM, Har Yip, C, Fuang Ho, G, Matsuo, K, Ito, H, Iwata, H, Tajima, K, Kang, D, Choi, JY, Park, SK, Yoo, KY, Maishman, T, Tapper, WJ, Dunning, A, Shah, M, Luben, R, Brown, J, Chuen Khor, C, Eccles, DM, Nevanlinna, H, Easton, D, Humphreys, K, Liu, J, Hall, P & Czene, K 2014, '2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy', Nature Communications, vol. 5, 4051. https://doi.org/10.1038/ncomms5051

TY - JOUR

T1 - 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

AU - Li, Jingmei

AU - Lindström, Linda S.

AU - Foo, Jia N.

AU - Rafiq, Sajjad

AU - Schmidt, Marjanka K.

AU - Pharoah, Paul D.P.

AU - Michailidou, Kyriaki

AU - Dennis, Joe

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Van'T Veer, Laura J.

AU - Cornelissen, Sten

AU - Rutgers, Emiel

AU - Southey, Melissa C.

AU - Apicella, Carmel

AU - Dite, Gillian S.

AU - Hopper, John L.

AU - Fasching, Peter A.

AU - Haeberle, Lothar

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Blomqvist, Carl

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Mannermaa, Arto

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Kataja, Vesa

AU - Chenevix-Trench, Georgia

AU - Investigators, Kconfab

AU - Phillips, Kelly Anne

AU - McLachlan, Sue Anne

AU - Lambrechts, Diether

AU - Thienpont, Bernard

AU - Smeets, Ann

AU - Wildiers, Hans

AU - Chang-Claude, Jenny

AU - Flesch-Janys, Dieter

AU - Seibold, Petra

AU - Rudolph, Anja

AU - Giles, Graham G.

AU - Baglietto, Laura

AU - Severi, Gianluca

AU - Haiman, Christopher A.

AU - Henderson, Brian E.

AU - Schumacher, Fredrick

AU - Le Marchand, Loic

AU - Kristensen, Vessela

AU - Alnæs, Grethe I.Grenaker

AU - Borresen-Dale, Anne Lise

AU - Nord, Silje

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Devilee, Peter

AU - Tollenaar, Robert

AU - Seynaeve, Caroline

AU - Hooning, Maartje

AU - Kriege, Mieke

AU - Hollestelle, Antoinette

AU - Van Den Ouweland, Ans

AU - Li, Yi

AU - Hamann, Ute

AU - Torres, Diana

AU - Ulmer, Hans U.

AU - Rüdiger, Thomas

AU - Shen, Chen Yang

AU - Hsiung, Chia Ni

AU - Wu, Pei Ei

AU - Chen, Shou Tung

AU - Teo, Soo Hwang

AU - Taib, Nur Aishah Mohd

AU - Har Yip, Cheng

AU - Fuang Ho, Gwo

AU - Matsuo, Keitaro

AU - Ito, Hidemi

AU - Iwata, Hiroji

AU - Tajima, Kazuo

AU - Kang, Daehee

AU - Choi, Ji Yeob

AU - Park, Sue K.

AU - Yoo, Keun Young

AU - Maishman, Tom

AU - Tapper, William J.

AU - Dunning, Alison

AU - Shah, Mitul

AU - Luben, Robert

AU - Brown, Judith

AU - Chuen Khor, Chiea

AU - Eccles, Diana M.

AU - Nevanlinna, Heli

AU - Easton, Douglas

AU - Humphreys, Keith

AU - Liu, Jianjun

AU - Hall, Per

AU - Czene, Kamila

N1 - Funding Information: The HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundatin and Bert von Kantzows foundation. 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, the Academy of Finland and by the strategic funding of the University of Eastern Finland. 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, Cancer Australia and the National Breast Cancer Foundation. K.A.P. is a National Breast Cancer Foundation Practitioner Fellow. L.M.B.C. is supported by the ‘Stichting tegen Kanker’ (232-2008 and 196-2010). 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 the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). 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 MEC was supported by NIH grants CA63464, CA54281, CA098758 and CA132839. The NBCS was supported by grants from the Norwegian Research council (155218/V40, 175240/S10 to A.L.B.D., FUGE-NFR 181600/V11 to V.N.K. and a Swizz Bridge Award to A.L.B.D.). The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu and the Oulu University Hospital. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). pKARMA is a combination of the KARMA and LIBRO-1 studies. KARMA was supported by Märit and Hans Rausings Initiative Against Breast Cancer. KARMA and LIBRO-1 were supported the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linnaeus Centre (Contract ID 70867902) financed by the Swedish Research Council. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. K.C. was financed by the Swedish Cancer Society (5128-B07-01PAF). SEARCH is funded by a programme grant from Cancer Research UK (C490/ A10124) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. SKKDKFZS is supported by the DKFZ. The TWBCS is supported by the Institute of Biomedical Sciences, Academia Sinica and the National Science Council, Taiwan. MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). The HERPACC was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by a research grant from Takeda Science Foundation, by the Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by the National Cancer Center Research and Development Fund. The SEBCS was supported by the Korea Health 21 R&D Project (AO30001), Ministry of Health and Welfare, Republic of Korea. POSH was supported by Funding Breast Cancer Campaign (NOV210PR62) and Cancer Research UK (C1275/A9896). 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. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and M.C.S. is a NHMRC Senior Research Fellow. D.F.E. is a Principal Research Fellow of CR-UK.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: We thank all the individuals who took part in these studies and all the researchers, study staff, clinicians and other health care providers, technicians and administrative staff who have enabled this work to be carried out. This work was financed by the Swedish Research Council (grant number: 521-2011-3187 and 524-2011-6857 to L.L.); Gösta Miltons Donationsfond to L.L., Swedish Cancer Society (grant number: CAN 2010/807 and 5128-B07-01PAF to K.C.) and a UNESCO-L’Oréal International Fellowship to J.L. This study was also supported by the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linneus Centre (Contract ID 70867902) financed by the Swedish Research Council. Funding for the iCOGS infrastructure came from: the European Community’s Seventh Framework Programme under grant agreement number 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. The ABCFS and OFBCR work was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The OFBCR work was also supported by the Canadian Institutes of Health Research ‘CIHR Team in Familial Risks of Breast Cancer’ programme. The ABCS was funded by Dutch Cancer Society grant numberNKI2007-3839; M.K.S. was funded by Dutch Cancer Society grant number NKI2009-4363. The work of the BBCC was partly funded by ELAN-Programme of the University Hospital of Erlangen. The BCAC is funded by CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). E.S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London, United Kingdom. I.T. is supported by the Oxford Biomedical Research Centre.

PY - 2014/6/17

Y1 - 2014/6/17

N2 - Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

AB - Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204-A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10 â ̂'9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

UR - http://www.scopus.com/inward/record.url?scp=84902763179&partnerID=8YFLogxK

U2 - 10.1038/ncomms5051

DO - 10.1038/ncomms5051

M3 - Article

C2 - 24937182

AN - SCOPUS:84902763179

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4051

ER -

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

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