Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
Year: 2019
Type: review
Study design: Observational Study
Abstract: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman’s total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. An estimated lifetime estrogen exposure (ELEE) model was defined using epidemiological data from EPIC-Italy ( n = 31,864). An epigenome-wide association study (EWAS) of ELEE was performed using existing Illumina HumanMethylation450K Beadchip (HM450K) methylation data obtained from EPIC-Italy blood DNA samples ( n = 216). A methylation index (MI) of ELEE based on 31 CpG sites was developed using HM450K data from EPIC-Italy and the Generations Study and evaluated for association with breast cancer risk in an independent dataset from the Generations Study ( n = 440 incident breast cancer cases matched to 440 healthy controls) using targeted bisulfite sequencing. Lastly, a meta-analysis was conducted including three additional cohorts, consisting of 1187 case-control pairs. We observed an estimated 5% increase in breast cancer risk per 1-year longer ELEE (OR = 1.05, 95% CI 1.04–1.07, P = 3 × 10 −12 ) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data (OR Q4_vs_Q1 = 1.77, 95% CI 1.07–2.93, P = 0.027) and in the meta-analysis (OR Q4_vs_Q1 = 1.43, 95% CI 1.05–2.00, P = 0.024); however, the correlation between the MI and ELEE was not validated across study cohorts. We have identified a blood DNA methylation signature associated with breast cancer risk in this study. Further investigation is required to confirm the interaction between estrogen exposure and DNA methylation in the blood.
Source: Clinical Epigenetics
Authors: Annelie Johansson, Domenico Palli, Giovanna Masala, Sara Grioni, Claudia Agnoli, Rosario Tumino, Maria Concetta Giurdanella, Francesca Fasanelli, Carlotta Sacerdote, Salvatore Panico, Amalia Mattiello, Silvia Polidoro, Michael E. Jones, Minouk J. Schoemaker, Nick Orr, Katarzyna Tomczyk, Nichola Johnson, Olivia Fletcher, Vittorio Perduca, Laura Baglietto, Pierre-Antoine Dugué, Melissa C. Southey, Graham G. Giles, Dallas R. English, Roger L. Milne, Gianluca Severi, Srikant Ambatipudi, Cyrille Cuenin, Veronique Chajès, Isabelle Romieu, Zdenko Herceg, Anthony J. Swerdlow, Paolo Vineis, James M. Flanagan
Institutions: Imperial College London, Fondazione IRCCS Istituto Nazionale dei Tumori, Piedmont Reference Center for Epidemiology and Cancer Prevention, Federico II University Hospital, University of Naples Federico II, Italian institute for Genomic Medicine, Institute of Cancer Research, Queen's University Belfast, Breast Cancer Now, Centre National de la Recherche Scientifique, Mathématiques Appliquées à Paris 5, Université Paris Descartes, University of Pisa, The University of Melbourne, Cancer Council Victoria, Monash Health, Monash University, Inserm, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Sree Chitra Thirunal Institute for Medical Sciences and Technology, Centre international de recherche sur le cancer, MRC Centre for Environment and Health
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
Funders: World Health Organization, Centre International de Recherche sur le Cancer, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Cancer Research UK, National Institute for Health and Care Research, Ovarian Cancer Action, European Commission, Fondation ARC pour la Recherche sur le Cancer, Institut National Du Cancer, Imperial Experimental Cancer Medicine Centre, Medical Research Council, National Health and Medical Research Council, Cancer Council Victoria
Awards: Health 2020, G2745390170, G3535040709, G3575964969, Methylation as a risk and prognostic factor for breast cancer, G3729156826, G3841306388, G3849299568, G3882005179, G4042319840, G5098929513, G5197845165, G543680480, G6008541153, G602992300, G6177794165, G62519578, G6341295889, Epidemiology of Chronic Disease, Health Interventions and DNA Studies, G7180840450, G7199237069, Precision Public Health for major cancers - novel approaches to building the genetic, epigenetic and lifestyle knowledge base for assessing risk and prognosis, G734127494, G8123808567, G8797697851, G8963950986
OpenAlex ID: W2947965693