Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies
Abstract Background DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-022-01554-8 |
| _version_ | 1811211616339886080 |
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| author | Pierre-Antoine Dugué Clara Bodelon Felicia F. Chung Hannah R. Brewer Srikant Ambatipudi Joshua N. Sampson Cyrille Cuenin Veronique Chajès Isabelle Romieu Giovanni Fiorito Carlotta Sacerdote Vittorio Krogh Salvatore Panico Rosario Tumino Paolo Vineis Silvia Polidoro Laura Baglietto Dallas English Gianluca Severi Graham G. Giles Roger L. Milne Zdenko Herceg Montserrat Garcia-Closas James M. Flanagan Melissa C. Southey |
| author_facet | Pierre-Antoine Dugué Clara Bodelon Felicia F. Chung Hannah R. Brewer Srikant Ambatipudi Joshua N. Sampson Cyrille Cuenin Veronique Chajès Isabelle Romieu Giovanni Fiorito Carlotta Sacerdote Vittorio Krogh Salvatore Panico Rosario Tumino Paolo Vineis Silvia Polidoro Laura Baglietto Dallas English Gianluca Severi Graham G. Giles Roger L. Milne Zdenko Herceg Montserrat Garcia-Closas James M. Flanagan Melissa C. Southey |
| author_sort | Pierre-Antoine Dugué |
| collection | DOAJ |
| description | Abstract Background DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. Methods Using data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. Results None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. Conclusion We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer. |
| first_indexed | 2024-04-12T05:15:44Z |
| format | Article |
| id | doaj.art-3d246a97622448d390bd92141db5bf5a |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-04-12T05:15:44Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-3d246a97622448d390bd92141db5bf5a2022-12-22T03:46:37ZengBMCBreast Cancer Research1465-542X2022-09-012411910.1186/s13058-022-01554-8Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studiesPierre-Antoine Dugué0Clara Bodelon1Felicia F. Chung2Hannah R. Brewer3Srikant Ambatipudi4Joshua N. Sampson5Cyrille Cuenin6Veronique Chajès7Isabelle Romieu8Giovanni Fiorito9Carlotta Sacerdote10Vittorio Krogh11Salvatore Panico12Rosario Tumino13Paolo Vineis14Silvia Polidoro15Laura Baglietto16Dallas English17Gianluca Severi18Graham G. Giles19Roger L. Milne20Zdenko Herceg21Montserrat Garcia-Closas22James M. Flanagan23Melissa C. Southey24Precision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityDivison of Cancer Epidemiology and Genetics, National Cancer InstituteInternational Agency for Research On Cancer (IARC)Department of Surgery and Cancer, Faculty of Medicine, Imperial College LondonInternational Agency for Research On Cancer (IARC)Divison of Cancer Epidemiology and Genetics, National Cancer InstituteInternational Agency for Research On Cancer (IARC)International Agency for Research On Cancer (IARC)International Agency for Research On Cancer (IARC)Department of Biomedical Sciences, University of SassariUnit of Cancer Epidemiology, Città della Salute e Della Scienza University-HospitalDepartment of Research, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di MilanoDipartimento di Medicina Clinica e Chirurgia Federico II UniversityHyblean Association for Epidemiological Research AIRE-ONLUSMRC Centre for Environment and Health, School of Public Health, Imperial College LondonItalian Institute for Genomic Medicine (IIGM)Department of Clinical and Experimental Medicine, University of PisaCancer Epidemiology Division, Cancer Council VictoriaCESP UMR1018, Paris-Saclay University, UVSQ, Inserm, Gustave RoussyPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityInternational Agency for Research On Cancer (IARC)Divison of Cancer Epidemiology and Genetics, National Cancer InstituteDepartment of Surgery and Cancer, Faculty of Medicine, Imperial College LondonPrecision Medicine, School of Clinical Sciences at Monash Health, Monash UniversityAbstract Background DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. Methods Using data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. Results None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. Conclusion We found no evidence that methylation-based measures of aging, smoking or alcohol consumption were associated with risk of breast cancer. A methylation-based marker of BMI was associated with risk and may provide insights into the underlying associations between BMI and breast cancer.https://doi.org/10.1186/s13058-022-01554-8Prospective studyDNA methylationEpigenetic agingLifestyleBreast cancer risk |
| spellingShingle | Pierre-Antoine Dugué Clara Bodelon Felicia F. Chung Hannah R. Brewer Srikant Ambatipudi Joshua N. Sampson Cyrille Cuenin Veronique Chajès Isabelle Romieu Giovanni Fiorito Carlotta Sacerdote Vittorio Krogh Salvatore Panico Rosario Tumino Paolo Vineis Silvia Polidoro Laura Baglietto Dallas English Gianluca Severi Graham G. Giles Roger L. Milne Zdenko Herceg Montserrat Garcia-Closas James M. Flanagan Melissa C. Southey Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies Breast Cancer Research Prospective study DNA methylation Epigenetic aging Lifestyle Breast cancer risk |
| title | Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies |
| title_full | Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies |
| title_fullStr | Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies |
| title_full_unstemmed | Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies |
| title_short | Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies |
| title_sort | methylation based markers of aging and lifestyle related factors and risk of breast cancer a pooled analysis of four prospective studies |
| topic | Prospective study DNA methylation Epigenetic aging Lifestyle Breast cancer risk |
| url | https://doi.org/10.1186/s13058-022-01554-8 |
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