dc.contributor.author | Johansson, A | |
dc.contributor.author | Palli, D | |
dc.contributor.author | Masala, G | |
dc.contributor.author | Grioni, S | |
dc.contributor.author | Agnoli, C | |
dc.contributor.author | Tumino, R | |
dc.contributor.author | Giurdanella, MC | |
dc.contributor.author | Fasanelli, F | |
dc.contributor.author | Sacerdote, C | |
dc.contributor.author | Panico, S | |
dc.contributor.author | Mattiello, A | |
dc.contributor.author | Polidoro, S | |
dc.contributor.author | Jones, ME | |
dc.contributor.author | Schoemaker, MJ | |
dc.contributor.author | Orr, N | |
dc.contributor.author | Tomczyk, K | |
dc.contributor.author | Johnson, N | |
dc.contributor.author | Fletcher, O | |
dc.contributor.author | Perduca, V | |
dc.contributor.author | Baglietto, L | |
dc.contributor.author | Dugué, P-A | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | English, DR | |
dc.contributor.author | Milne, RL | |
dc.contributor.author | Severi, G | |
dc.contributor.author | Ambatipudi, S | |
dc.contributor.author | Cuenin, C | |
dc.contributor.author | Chajès, V | |
dc.contributor.author | Romieu, I | |
dc.contributor.author | Herceg, Z | |
dc.contributor.author | Swerdlow, AJ | |
dc.contributor.author | Vineis, P | |
dc.contributor.author | Flanagan, JM | |
dc.date.accessioned | 2019-11-01T10:42:25Z | |
dc.date.issued | 2019-04-30 | |
dc.identifier.citation | Clinical epigenetics, 2019, 11 (1), pp. 66 - ? | |
dc.identifier.issn | 1868-7075 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3401 | |
dc.identifier.eissn | 1868-7083 | |
dc.identifier.doi | 10.1186/s13148-019-0664-7 | |
dc.description.abstract | BACKGROUND: 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. METHODS: 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. RESULTS: 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 (ORQ4_vs_Q1 = 1.77, 95% CI 1.07-2.93, P = 0.027) and in the meta-analysis (ORQ4_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. CONCLUSION: 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. | |
dc.format | Electronic | |
dc.format.extent | 66 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Estrogens | |
dc.subject | Case-Control Studies | |
dc.subject | Prospective Studies | |
dc.subject | DNA Methylation | |
dc.subject | Epigenesis, Genetic | |
dc.subject | CpG Islands | |
dc.subject | Middle Aged | |
dc.subject | Italy | |
dc.subject | Female | |
dc.subject | Genome-Wide Association Study | |
dc.title | Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-04-09 | |
rioxxterms.versionofrecord | 10.1186/s13148-019-0664-7 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-04-30 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical epigenetics | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology | |
pubs.publication-status | Published | |
pubs.volume | 11 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Aetiological Epidemiology | |
dc.contributor.icrauthor | Jones, Michael | |
dc.contributor.icrauthor | Schoemaker, Minouk | |
dc.contributor.icrauthor | Fletcher, Olivia | |