Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk

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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Johansson, Annelie [verfasserIn] Palli, Domenico Masala, Giovanna Grioni, Sara Agnoli, Claudia Tumino, Rosario Giurdanella, Maria Concetta Fasanelli, Francesca Sacerdote, Carlotta Panico, Salvatore Mattiello, Amalia Polidoro, Silvia Jones, Michael E. Schoemaker, Minouk J. Orr, Nick Tomczyk, Katarzyna Johnson, Nichola Fletcher, Olivia Perduca, Vittorio Baglietto, Laura Dugué, Pierre-Antoine Southey, Melissa C. Giles, Graham G. English, Dallas R. Milne, Roger L. Severi, Gianluca Ambatipudi, Srikant Cuenin, Cyrille Chajès, Veronique Romieu, Isabelle Herceg, Zdenko Swerdlow, Anthony J. Vineis, Paolo Flanagan, James M.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	DNA methylation EWAS Epigenetics Breast cancer Cancer risk Estrogen exposure Hormonal exposures Biomarker

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Clinical epigenetics - [S.l.] : BioMed Central, 2010, 11(2019), 1 vom: 30. Apr.
Übergeordnetes Werk:	volume:11 ; year:2019 ; number:1 ; day:30 ; month:04

Links:	Volltext

DOI / URN:	10.1186/s13148-019-0664-7

Katalog-ID:	SPR030678358

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520			\|a 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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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.
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allfields	10.1186/s13148-019-0664-7 doi (DE-627)SPR030678358 (SPR)s13148-019-0664-7-e DE-627 ger DE-627 rakwb eng Johansson, Annelie verfasserin aut Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. DNA methylation (dpeaa)DE-He213 EWAS (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Cancer risk (dpeaa)DE-He213 Estrogen exposure (dpeaa)DE-He213 Hormonal exposures (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Palli, Domenico aut Masala, Giovanna aut Grioni, Sara aut Agnoli, Claudia aut Tumino, Rosario aut Giurdanella, Maria Concetta aut Fasanelli, Francesca aut Sacerdote, Carlotta aut Panico, Salvatore aut Mattiello, Amalia aut Polidoro, Silvia aut Jones, Michael E. aut Schoemaker, Minouk J. aut Orr, Nick aut Tomczyk, Katarzyna aut Johnson, Nichola aut Fletcher, Olivia aut Perduca, Vittorio aut Baglietto, Laura aut Dugué, Pierre-Antoine aut Southey, Melissa C. aut Giles, Graham G. aut English, Dallas R. aut Milne, Roger L. aut Severi, Gianluca aut Ambatipudi, Srikant aut Cuenin, Cyrille aut Chajès, Veronique aut Romieu, Isabelle aut Herceg, Zdenko aut Swerdlow, Anthony J. aut Vineis, Paolo aut Flanagan, James M. (orcid)0000-0003-4955-1383 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 30. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:30 month:04 https://dx.doi.org/10.1186/s13148-019-0664-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 1 30 04
spelling	10.1186/s13148-019-0664-7 doi (DE-627)SPR030678358 (SPR)s13148-019-0664-7-e DE-627 ger DE-627 rakwb eng Johansson, Annelie verfasserin aut Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. DNA methylation (dpeaa)DE-He213 EWAS (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Cancer risk (dpeaa)DE-He213 Estrogen exposure (dpeaa)DE-He213 Hormonal exposures (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Palli, Domenico aut Masala, Giovanna aut Grioni, Sara aut Agnoli, Claudia aut Tumino, Rosario aut Giurdanella, Maria Concetta aut Fasanelli, Francesca aut Sacerdote, Carlotta aut Panico, Salvatore aut Mattiello, Amalia aut Polidoro, Silvia aut Jones, Michael E. aut Schoemaker, Minouk J. aut Orr, Nick aut Tomczyk, Katarzyna aut Johnson, Nichola aut Fletcher, Olivia aut Perduca, Vittorio aut Baglietto, Laura aut Dugué, Pierre-Antoine aut Southey, Melissa C. aut Giles, Graham G. aut English, Dallas R. aut Milne, Roger L. aut Severi, Gianluca aut Ambatipudi, Srikant aut Cuenin, Cyrille aut Chajès, Veronique aut Romieu, Isabelle aut Herceg, Zdenko aut Swerdlow, Anthony J. aut Vineis, Paolo aut Flanagan, James M. (orcid)0000-0003-4955-1383 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 30. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:30 month:04 https://dx.doi.org/10.1186/s13148-019-0664-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 1 30 04
allfields_unstemmed	10.1186/s13148-019-0664-7 doi (DE-627)SPR030678358 (SPR)s13148-019-0664-7-e DE-627 ger DE-627 rakwb eng Johansson, Annelie verfasserin aut Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. DNA methylation (dpeaa)DE-He213 EWAS (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Cancer risk (dpeaa)DE-He213 Estrogen exposure (dpeaa)DE-He213 Hormonal exposures (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Palli, Domenico aut Masala, Giovanna aut Grioni, Sara aut Agnoli, Claudia aut Tumino, Rosario aut Giurdanella, Maria Concetta aut Fasanelli, Francesca aut Sacerdote, Carlotta aut Panico, Salvatore aut Mattiello, Amalia aut Polidoro, Silvia aut Jones, Michael E. aut Schoemaker, Minouk J. aut Orr, Nick aut Tomczyk, Katarzyna aut Johnson, Nichola aut Fletcher, Olivia aut Perduca, Vittorio aut Baglietto, Laura aut Dugué, Pierre-Antoine aut Southey, Melissa C. aut Giles, Graham G. aut English, Dallas R. aut Milne, Roger L. aut Severi, Gianluca aut Ambatipudi, Srikant aut Cuenin, Cyrille aut Chajès, Veronique aut Romieu, Isabelle aut Herceg, Zdenko aut Swerdlow, Anthony J. aut Vineis, Paolo aut Flanagan, James M. (orcid)0000-0003-4955-1383 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 30. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:30 month:04 https://dx.doi.org/10.1186/s13148-019-0664-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 1 30 04
allfieldsGer	10.1186/s13148-019-0664-7 doi (DE-627)SPR030678358 (SPR)s13148-019-0664-7-e DE-627 ger DE-627 rakwb eng Johansson, Annelie verfasserin aut Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. DNA methylation (dpeaa)DE-He213 EWAS (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Cancer risk (dpeaa)DE-He213 Estrogen exposure (dpeaa)DE-He213 Hormonal exposures (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Palli, Domenico aut Masala, Giovanna aut Grioni, Sara aut Agnoli, Claudia aut Tumino, Rosario aut Giurdanella, Maria Concetta aut Fasanelli, Francesca aut Sacerdote, Carlotta aut Panico, Salvatore aut Mattiello, Amalia aut Polidoro, Silvia aut Jones, Michael E. aut Schoemaker, Minouk J. aut Orr, Nick aut Tomczyk, Katarzyna aut Johnson, Nichola aut Fletcher, Olivia aut Perduca, Vittorio aut Baglietto, Laura aut Dugué, Pierre-Antoine aut Southey, Melissa C. aut Giles, Graham G. aut English, Dallas R. aut Milne, Roger L. aut Severi, Gianluca aut Ambatipudi, Srikant aut Cuenin, Cyrille aut Chajès, Veronique aut Romieu, Isabelle aut Herceg, Zdenko aut Swerdlow, Anthony J. aut Vineis, Paolo aut Flanagan, James M. (orcid)0000-0003-4955-1383 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 30. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:30 month:04 https://dx.doi.org/10.1186/s13148-019-0664-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 1 30 04
allfieldsSound	10.1186/s13148-019-0664-7 doi (DE-627)SPR030678358 (SPR)s13148-019-0664-7-e DE-627 ger DE-627 rakwb eng Johansson, Annelie verfasserin aut Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. DNA methylation (dpeaa)DE-He213 EWAS (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Cancer risk (dpeaa)DE-He213 Estrogen exposure (dpeaa)DE-He213 Hormonal exposures (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213 Palli, Domenico aut Masala, Giovanna aut Grioni, Sara aut Agnoli, Claudia aut Tumino, Rosario aut Giurdanella, Maria Concetta aut Fasanelli, Francesca aut Sacerdote, Carlotta aut Panico, Salvatore aut Mattiello, Amalia aut Polidoro, Silvia aut Jones, Michael E. aut Schoemaker, Minouk J. aut Orr, Nick aut Tomczyk, Katarzyna aut Johnson, Nichola aut Fletcher, Olivia aut Perduca, Vittorio aut Baglietto, Laura aut Dugué, Pierre-Antoine aut Southey, Melissa C. aut Giles, Graham G. aut English, Dallas R. aut Milne, Roger L. aut Severi, Gianluca aut Ambatipudi, Srikant aut Cuenin, Cyrille aut Chajès, Veronique aut Romieu, Isabelle aut Herceg, Zdenko aut Swerdlow, Anthony J. aut Vineis, Paolo aut Flanagan, James M. (orcid)0000-0003-4955-1383 aut Enthalten in Clinical epigenetics [S.l.] : BioMed Central, 2010 11(2019), 1 vom: 30. Apr. (DE-627)626459028 (DE-600)2553921-8 1868-7083 nnns volume:11 year:2019 number:1 day:30 month:04 https://dx.doi.org/10.1186/s13148-019-0664-7 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2019 1 30 04
language	English
source	Enthalten in Clinical epigenetics 11(2019), 1 vom: 30. Apr. volume:11 year:2019 number:1 day:30 month:04
sourceStr	Enthalten in Clinical epigenetics 11(2019), 1 vom: 30. Apr. volume:11 year:2019 number:1 day:30 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	DNA methylation EWAS Epigenetics Breast cancer Cancer risk Estrogen exposure Hormonal exposures Biomarker
isfreeaccess_bool	true
container_title	Clinical epigenetics
authorswithroles_txt_mv	Johansson, Annelie @@aut@@ Palli, Domenico @@aut@@ Masala, Giovanna @@aut@@ Grioni, Sara @@aut@@ Agnoli, Claudia @@aut@@ Tumino, Rosario @@aut@@ Giurdanella, Maria Concetta @@aut@@ Fasanelli, Francesca @@aut@@ Sacerdote, Carlotta @@aut@@ Panico, Salvatore @@aut@@ Mattiello, Amalia @@aut@@ Polidoro, Silvia @@aut@@ Jones, Michael E. @@aut@@ Schoemaker, Minouk J. @@aut@@ Orr, Nick @@aut@@ Tomczyk, Katarzyna @@aut@@ Johnson, Nichola @@aut@@ Fletcher, Olivia @@aut@@ Perduca, Vittorio @@aut@@ Baglietto, Laura @@aut@@ Dugué, Pierre-Antoine @@aut@@ Southey, Melissa C. @@aut@@ Giles, Graham G. @@aut@@ English, Dallas R. @@aut@@ Milne, Roger L. @@aut@@ Severi, Gianluca @@aut@@ Ambatipudi, Srikant @@aut@@ Cuenin, Cyrille @@aut@@ Chajès, Veronique @@aut@@ Romieu, Isabelle @@aut@@ Herceg, Zdenko @@aut@@ Swerdlow, Anthony J. @@aut@@ Vineis, Paolo @@aut@@ Flanagan, James M. @@aut@@
publishDateDaySort_date	2019-04-30T00:00:00Z
hierarchy_top_id	626459028
id	SPR030678358
language_de	englisch
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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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. Conclusion We have identified a blood DNA methylation signature associated with breast cancer risk in this study. 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author	Johansson, Annelie
spellingShingle	Johansson, Annelie misc DNA methylation misc EWAS misc Epigenetics misc Breast cancer misc Cancer risk misc Estrogen exposure misc Hormonal exposures misc Biomarker Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
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topic_title	Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk DNA methylation (dpeaa)DE-He213 EWAS (dpeaa)DE-He213 Epigenetics (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 Cancer risk (dpeaa)DE-He213 Estrogen exposure (dpeaa)DE-He213 Hormonal exposures (dpeaa)DE-He213 Biomarker (dpeaa)DE-He213
topic	misc DNA methylation misc EWAS misc Epigenetics misc Breast cancer misc Cancer risk misc Estrogen exposure misc Hormonal exposures misc Biomarker
topic_unstemmed	misc DNA methylation misc EWAS misc Epigenetics misc Breast cancer misc Cancer risk misc Estrogen exposure misc Hormonal exposures misc Biomarker
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title	Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
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title_full	Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
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author_browse	Johansson, Annelie Palli, Domenico Masala, Giovanna Grioni, Sara Agnoli, Claudia Tumino, Rosario Giurdanella, Maria Concetta Fasanelli, Francesca Sacerdote, Carlotta Panico, Salvatore Mattiello, Amalia Polidoro, Silvia Jones, Michael E. Schoemaker, Minouk J. Orr, Nick Tomczyk, Katarzyna Johnson, Nichola Fletcher, Olivia Perduca, Vittorio Baglietto, Laura Dugué, Pierre-Antoine Southey, Melissa C. Giles, Graham G. English, Dallas R. Milne, Roger L. Severi, Gianluca Ambatipudi, Srikant Cuenin, Cyrille Chajès, Veronique Romieu, Isabelle Herceg, Zdenko Swerdlow, Anthony J. Vineis, Paolo Flanagan, James M.
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title_sort	epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
title_auth	Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. © The Author(s). 2019
abstractGer	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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. © The Author(s). 2019
abstract_unstemmed	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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. 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. © The Author(s). 2019
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title_short	Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR030678358</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519071104.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2019 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13148-019-0664-7</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR030678358</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s13148-019-0664-7-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Johansson, Annelie</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2019</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2019</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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} $) in EPIC-Italy. The EWAS identified 694 CpG sites associated with ELEE (FDR Q < 0.05). We report a DNA methylation index (MI) associated with breast cancer risk that is validated in the Generations Study targeted bisulfite sequencing data ($ 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. Conclusion We have identified a blood DNA methylation signature associated with breast cancer risk in this study. 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Epigenome-wide association study for lifetime estrogen exposure identifies an epigenetic signature associated with breast cancer risk

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