Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

Journal article


Publication Details

Author(s): Yang Y, Wu L, Shu X, Lu Y, Shu XO, Cai Q, Beeghly-Fadiel A, Li B, Ye F, Berchuck A, Anton-Culver H, Banerjee S, Benitez J, Bjorge L, Brenton JD, Butzow R, Campbell IG, Chang-Claude J, Chen K, Cook LS, Cramer DW, Defazio A, Dennis J, Doherty JA, Doerk T, Eccles DM, Edwards DV, Fasching P, Fortner RT, Gayther SA, Giles GG, Glasspool RM, Goode EL, Goodman MT, Gronwald J, Harris HR, Heitz F, Hildebrandt MA, Hogdall E, Hogdall CK, Huntsman DG, Kar SP, Karlan BY, Kelemen LE, Kiemeney LA, Kjaer SK, Koushik A, Lambrechts D, Le ND, Levine DA, Massuger LF, Matsuo K, May T, Mcneish IA, Menon U, Modugno F, Monteiro AN, Moorman PG, Moysich KB, Ness RB, Nevanlinna H, Olsson H, Onland-Moret NC, Park SK, Paul J, Pearce CL, Pejovic T, Phelan CM, Pike MC, Ramus SJ, Riboli E, Rodriguez-Antona C, Romieu I, Sandler DP, Schildkraut JM, Setiawan VW, Shan K, Siddiqui N, Sieh W, Stampfer MJ, Sutphen R, Swerdlow AJ, Szafron LM, Teo SH, Tworoger SS, Tyrer JP, Webb PM, Wentzensen N, White E, Willett WC, Wolk A, Woo YL, Wu AH, Yan L, Yannoukakos D, Chenevix-Trench G, Sellers TA, Pharoah PDP, Zheng W, Long J
Journal: Cancer Research
Publication year: 2019
Volume: 79
Journal issue: 3
ISSN: 0008-5472


Abstract

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.


FAU Authors / FAU Editors

Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


External institutions with authors

Aichi Cancer Center Research Institute
BC Cancer
Beatson West of Scotland Cancer Centre (BWSCC)
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cancer Council Victoria
Cancer Research Initiatives Foundation (CARIF)
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Fred Hutchinson Cancer Research Center
Glasgow Royal Infirmary (GRI)
Hannover Medical School / Medizinische Hochschule Hannover (MHH)
Harvard University
Haukeland University Hospital / Haukeland universitetssykehus
Hebei Medical University / 河北医科大学
HELIOS Kliniken
Helsingin yliopisto / University of Helsinki
H. Lee Moffitt Cancer Center & Research Institute
Icahn School of Medicine at Mount Sinai
Imperial College London / The Imperial College of Science, Technology and Medicine
International Agency for Research on Cancer (IARC)
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Lund University / Lunds universitet
Magee-Womens Foundation
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
National Centre for Scientific Research (NCSR) "Demokritos"
National Institute of Environmental Health Sciences (NIEHS)
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Roswell Park Cancer Institute
Seoul National University (SNU) / 서울대학교
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
The Institute of Cancer Research (ICR)
The Royal Marsden NHS Foundation Trust
Tianjin Medical University (TMU) / 天津医科大学
Université de Montréal
Universiteit Utrecht (UU) / Utrecht University
University College London (UCL)
University Health Network (UHN)
University of California Irvine
University of Cambridge
University of Copenhagen
University of Malaya (UM) / Universiti Malaya
University of Michigan
University of New Mexico
University of New South Wales (UNSW)
University of Southampton
University of Southern California (USC)
University of South Florida (USF)
University of Sydney
University of Texas Health Science Center at Houston (UTHealth)
University of Texas MD Anderson Cancer Center
University of Utah
University of Virginia (UVA)
Vanderbilt University


How to cite

APA:
Yang, Y., Wu, L., Shu, X., Lu, Y., Shu, X.-O., Cai, Q.,... Long, J. (2019). Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk. Cancer Research, 79(3). https://dx.doi.org/10.1158/0008-5472.CAN-18-2726

MLA:
Yang, Yaohua, et al. "Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk." Cancer Research 79.3 (2019).

BibTeX: 

Last updated on 2019-27-03 at 18:23