Journal article

A Mendelian randomization analysis of circulating lipid traits and breast cancer risk

Alicia Beeghly-Fadiel, Nikhil K Khankari, Ryan J Delahanty, Xiao-Ou Shu, Yingchang Lu, Marjanka K Schmidt, Manjeet K Bolla, Kyriaki Michailidou, Qin Wang, Joe Dennis, Drakoulis Yannoukakos, Alison M Dunning, Paul DP Pharoah, Georgia Chenevix-Trench, Roger L Milne, David J Hunter, Hall Per, Peter Kraft, Jacques Simard, Douglas F Easton Show all

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | OXFORD UNIV PRESS | Published : 2020

Abstract

BACKGROUND: Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. METHODS: Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a..

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Grants

Awarded by National Cancer Institute at the National Institutes of Health


Awarded by National Institutes of Health


Awarded by Cancer Research UK


Awarded by European Community's Seventh Framework Programme


Awarded by Post-Cancer GWAS initiative


Awarded by Department of Defense


Awarded by NIH


Awarded by Cancer UK Grant


Awarded by Canadian Institutes of Health Research


Awarded by National Institutes of Health (USA)


Awarded by Dutch Cancer Society


Awarded by Dutch government


Awarded by Fondo de Investigacion Sanitario


Awarded by California Breast Cancer Research Fund


Awarded by California Department of Public Health as part of the statewide cancer reporting programme


Awarded by Lon V Smith Foundation


Awarded by Deutsche Krebshilfe


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


Awarded by Stichting tegen Kanker


Awarded by Deutsche Krebshilfe e.V.


Awarded by National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer


Awarded by Australian NHMRC


Awarded by Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program


Awarded by Ministry of Economic Development, Innovation and Export Trade


Awarded by Norwegian Research council


Awarded by Academy of Finland


Awarded by Academy of Finland (Center of Excellence)


Awarded by Biobanking and Biomolecular Resources Research Infrastructure


Awarded by Specialized Program of Research Excellence (SPORE) in Breast Cancer


Awarded by Hellenic Cooperative Oncology Group research grant



Funding Acknowledgements

This work was supported by a National Cancer Institute at the National Institutes of Health research grant (R37CA070867) and endowment funds for the Ingram Professorship and Anne Potter Wilson Chair. N.K.K. was supported by a National Institutes of Health training grant (R25CA160056). BCAC is funded by Cancer Research UK (C1287/A16563, C1287/A12014) and by the European Communit~ys Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n~ 223175 (HEALTH-F2-2009-223175) (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 (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 -the GAME-ON initiative), the Department of Defense (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. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer 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 Ministe`re de l'E ' conomie, Science et Innovation du Que ' bec through Genome Que ' bec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by the National Institutes of Health (USA) (UM1 CA164920). The content of this manuscript does not necessarily reflect the views or policies of the National Institutes of Health or any of the collaborating centres 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) Australia Fellow and 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) and BBMRINL, which is a Research Infrastructure financed by the Dutch government (NWO 184.021.007). The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. 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). E.J.S. (BIGGS) is supported by NIHR Comprehensive Biomedical Research Centre, Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London, UK; I.T. is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Se ' curite ' Sanitaire (ANSES) and Agence Nationale de la Recherche (ANR).The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital. The CNIOBCS was supported by the Spanish Network on Rare Diseases (CIBERER) and grants from the Asociacio ' n Espa~nola Contra el Ca ' ncer and the Fondo de Investigacio ' n Sanitario (PI11/00923 and PI12/00070). The Human Genotyping-CEGEN Unit (CNIO) is supported by the Instituto de Salud Carlos III. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting programme mandated by California Health and Safety Code Section 103885. H.A.C. receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Wu<spacing diaeresis> rttemberg 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). The GC-HBOC was supported by Deutsche Krebshilfe (107 352). 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, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance and Institute of the RuhrUniversity Bochum (IPA), as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus Bonn, Germany. HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HMBCS was supported by the Rudolf Bartling 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 foundation 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 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. LMBC is supported by the `Stichting tegen Kanker' (2322008 and 196-2010); D.L.s is supported by the FWO and the KULPFV/10/016-SymBioSysII and by an ERC consolidator grant. The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I, 106332, 108253, 108419), the Hamburg Cancer Society, the German Cancer Research Center (DKFZ), and the Federal Ministry of Education and Research (BMBF) Germany (01KH0402).MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects `5x1000'). The MCBCS was supported by National Institutes of Health grants (CA116167, CA176785, CA192393) a National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. 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 support by National Institutes of Health grants (CA63464, CA54281, CA098758 and CA132839). The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the `CIHR Team in Familial Risks of Breast Cancer' program (grant #CRN-87521) and the Ministry of Economic Development, Innovation and Export Trade (grant #PSR-SIIRI-701). 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 ALBD). The NBHS was supported by National Institutes of Health (R01CA100374); biological sample preparation was conducted by the Survey and Biospecimen Shared Resource, which is supported by National Institutes of Health (P30 CA68485). 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 OFBCR was supported by National Institutes of Health (UM1 CA164920). The content of this manuscript does not necessarily reflect the views or policies of the National Institutes of Health or any of the collaborating centres 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 ORIGO study was supported by the Dutch Cancer Society (RUL 19971505) 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. The pKARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. 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 (A*STAR), the US National Institute of Health and the Susan G Komen Breast Cancer Foundation. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and the 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 P.D.P.P. from the NHS in the East of England through the Clinical Academic Reserve. SKKDKFZS is supported by the DKFZ.The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F and Margaret T Grohne Family Foundation, the Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, the European Union (European Social Fund -ESF), and Greek national funds through the Operational Program `Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) -ARISTEIA. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. I.C.R. acknowledges NHS funding to the NIHR Biomedical Research Centre.