Journal
CANCER RESEARCH
Volume 79, Issue 3, Pages 505-517Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-18-2726
Keywords
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Categories
Funding
- Breast Cancer Now
- Institute of Cancer Research (ICR)
- NHS
- Vanderbilt CTSA from NCATS/NIH [UL1TR000445]
- Cancer Research UK
- University of Cambridge
- National Institute for Health Research Cambridge Biomedical Research Centre
- Innovative Research Team in University (PCSIRT) in China [IRT1076]
- Gynecologic Cancer Center of Excellence [W81XWH-11-2-0131]
- Dutch Cancer Society [EMC 2014-6699, EMC 20146699]
- Helsinki University Research Fund
- JSPS KAKENHI grant
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)
- National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [HI16C1127, 0920010]
- Malaysian Ministry of Higher Education (UM.C/HIR/MOHE/06)
- Cancer Research Initiatives Foundation
- VicHealth
- Cancer Council Victoria
- Australian NHMRC grants [209057, 251553, 504711]
- NCI designated Comprehensive Cancer Center [P30-CA076292]
- NIH [P50 CA159981, R01CA126841, R37-CA070867, U19-CA148112, R01-CA149429, R01-CA058598, RO1-CA142081, R01-CA063678, R01-CA074850, R01-CA080742, R01CA112523, R01-CA87538, R01-CA58598]
- Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES044005, Z01-ES049033]
- National Health Research and Development Program, Health Canada [6613-1415-53]
- NIH, NCI [CA58860]
- Lon V Smith Foundation grant [LVS-39420]
- National Health and Medical Research Council [310670, 628903]
- Cancer Institute NSW grants [12/RIG/1-17, 15/RIG/1-16]
- Department of Medicine at Vanderbilt University Medical Center
- Ovarian Cancer Research Fund
- US National Cancer Institute GAME-ON Post-GWAS Initiative [U19-CA148112]
- Wellcome Trust [076113]
- Canadian Institutes of Health Research [MOP-86727]
- Canadian Institutes of Health Research (Ovarian Cancer Research Fund)
- European Commission [223175 - HEALTH-F2-2009-223175]
- U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729]
- National Health & Medical Research Council of Australia [199600, 400413, 400281]
- Cancer Council of New South Wales
- Cancer Council of Victoria
- Cancer Council of Queensland
- Cancer Council of South Australia
- Cancer Council of Tasmania
- Cancer Foundation of Western Australia [191, 211, 182]
- Ovarian Cancer Australia
- Peter MacCallum Foundation
- ELAN Funds of the University of Erlangen-Nuremberg
- National Kankerplan
- Breast Cancer Now, Institute of Cancer Research
- Vanderbilt CTSA grant from the NIH/National Center for Advancing Translational Sciences (NCATS) [ULTR000445]
- National Institutes of Health Research Cambridge Biomedical Research Centre
- Cancer Research UK Cambridge Cancer Centre
- Innovative Research Team at the University (PCSIRT) in China [IRT1076]
- Instituto de Salud Carlos III [PI 12/01319]
- Ministerio de Economia y Competitividad (SAF2012)
- Department of Defense [W81XWH-11-2-0131, DAMD17-02-1-0666, DAMD17-02-1-0669]
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer (France)
- Institut Gustave Roussy (France)
- Mutuelle Generale de l'Education Nationale (France)
- Institut National de la Sante et de la Recherche Medicale (INSERM
- France)
- German Cancer Aid (Germany)
- German Cancer Research Center (DKFZ) (Germany)
- Federal Ministry of Education and Research (BMBF
- Germany)
- Hellenic Health Foundation (Greece)
- Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy
- National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands)
- Netherlands Cancer Registry (NKR) (The Netherlands)
- LK Research Funds (The Netherlands)
- Dutch Prevention Funds (The Netherlands)
- Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands)
- World Cancer Research Fund (WCRF) (The Netherlands)
- Statistics Netherlands (The Netherlands)
- Nordforsk (Norway)
- Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway)
- Health Research Fund (FIS) (Spain) [PI13/00061, PI13/01162]
- Regional Government of Andalucia (Spain)
- Regional Government of Asturias (Spain)
- Regional Government of Basque Country (Spain)
- Regional Government of Murcia (Spain)
- Regional Government of Navarra (Spain)
- ISCIII RETIC (Spain) [RD06/0020]
- Swedish Cancer Society (Sweden)
- Swedish Research Council (Sweden)
- County Council of Skane (Sweden)
- County Council of Vasterbotten (Sweden)
- Cancer Research UK (United Kingdom) [14136, C570/A16491, C8221/A19170]
- Medical Research Council (United Kingdom) [1000143, MR/M012190/1]
- German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research [01 GB 9401]
- German Cancer Research Center (DKFZ)
- European Union (European Social Fund -ESF)
- Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) -Research Funding Program of the General Secretariat for Research Technology. Investing in knowledge society through the European Social Fund [SYN11_10_19 NBCA]
- Roswell Park Cancer Institute Alliance Foundation [P30 CA016056]
- Rudolf-Bartling Foundation
- NCI [K07-CA080668, R01-CA95023, P50-CA159981, MO1-RR000056, R01-CA126841]
- Ministry of Health, Labour and Welfare
- American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]
- National Center for Advancing Translational Sciences (NCATS) [UL1TR000124]
- Swedish Cancer Society
- Swedish Research Council
- Beta Kamprad Foundation
- Mayo Foundation
- Minnesota Ovarian Cancer Alliance
- Fred C. and Katherine B. Andersen Foundation
- Fraternal Order of Eagles
- NCI, Bethesda, MD [R01-CA61107]
- Danish Cancer Society, Copenhagen, Denmark [94 222 52]
- Mermaid I project
- Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06)
- National Health and Medical Research Council of Australia (NHMRC) [209057, 251533, 396414, 504715]
- DOD Ovarian Cancer Research Program [W81XWH-07-0449]
- Moffitt Cancer Center
- Merck Pharmaceuticals
- state of Florida
- Hillsborough County
- city of Tampa
- National Cancer Institute [NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, P30-CA072720]
- Cancer Institute of New Jersey
- Helse Vest
- Norwegian Cancer Society
- Research Council of Norway
- Radboud University Medical Centre
- National Health and Medical Research Council (NHMRC) of Australia [APP1025142]
- Brisbane Women's Club
- OHSU Foundation
- NIH/NCI [1 R01CA160669-01A1]
- Intramural Research Program of the National Cancer Institute
- Pomeranian Medical University
- Canadian Cancer Society
- Cancer Research Society GRePEC Program
- National Health and Medical Research Council of Australia
- Royal Marsden Hospital
- Cancer Research UK [C490/A10119 C490/A10124, C536/A13086, C536/A6689, C490/A6187]
- UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge
- NIH, National Institute of Environmental Health Sciences [Z01-ES049033, Z01 ES044005]
- Imperial Experimental Cancer Research Centre [C1312/A15589]
- Swedish Cancer foundation
- WeCanCureCancer
- arKampMotCancer foundation
- NIH (NCI) grant [R37-CA070867]
- American Cancer Society [CRTG-00-196-01-CCE]
- Celma Mastery Ovarian Cancer Foundation
- Princess Margaret Cancer Centre Foundation Bridge for the Cure
- Eve Appeal (The Oak Foundation)
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- California Cancer Research Program [00-01389V-20170, 2II0200]
- BC Cancer Foundation
- VGH & UBC Hospital Foundation
- National Health and Medical Research Council of Australia [310670, 628903]
- National Science Centren [N N301 5645 40]
- Maria Sklodowska-Curie Memorial Cancer Center
- Institute of Oncology, Warsaw, Poland
- [1S10RR025141-01]
- [ERC-2009-AdG 232997]
- [ERC-2011-AdG 294576]
- [P01CA17054]
- [P30CA14089]
- [R01CA61132]
- [N01PC67010]
- [R03CA113148]
- [R03CA115195]
- [N01CN025403]
- [UM1 CA186107]
- [P01 CA87969]
- [R01 CA49449]
- [R01-CA67262]
- [UM1 CA176726]
- [N01-CN-55424]
- [N01-PC-67001]
- [R01-CA122443]
- [P30-CA15083]
- [P50-CA136393]
- [CA54281]
- [CA164973]
- [CA63464]
- [R01-CA76016]
- [R01-CA106414-A2]
- [R01 CA063678]
- [R01 CA063682]
- [R01-CA058860]
- [K05-CA154337]
- MRC [G0601891, G0501974, MR/N003284/1] Funding Source: UKRI
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES044005] Funding Source: NIH RePORTER
- Korea Health Promotion Institute [0920010] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
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