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Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies.
Dugué, Pierre-Antoine; Bodelon, Clara; Chung, Felicia F; Brewer, Hannah R; Ambatipudi, Srikant; Sampson, Joshua N; Cuenin, Cyrille; Chajès, Veronique; Romieu, Isabelle; Fiorito, Giovanni; Sacerdote, Carlotta; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Polidoro, Silvia; Baglietto, Laura; English, Dallas; Severi, Gianluca; Giles, Graham G; Milne, Roger L; Herceg, Zdenko; Garcia-Closas, Montserrat; Flanagan, James M; Southey, Melissa C.
Affiliation
  • Dugué PA; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia. pierre-antoine.dugue@monash.edu.
  • Bodelon C; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia. pierre-antoine.dugue@monash.edu.
  • Chung FF; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia. pierre-antoine.dugue@monash.edu.
  • Brewer HR; Divison of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
  • Ambatipudi S; International Agency for Research On Cancer (IARC), Lyon, France.
  • Sampson JN; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Malaysia.
  • Cuenin C; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
  • Chajès V; International Agency for Research On Cancer (IARC), Lyon, France.
  • Romieu I; AMCHSS, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.
  • Fiorito G; Divison of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
  • Sacerdote C; International Agency for Research On Cancer (IARC), Lyon, France.
  • Krogh V; International Agency for Research On Cancer (IARC), Lyon, France.
  • Panico S; International Agency for Research On Cancer (IARC), Lyon, France.
  • Tumino R; Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
  • Vineis P; MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Polidoro S; Unit of Cancer Epidemiology, Città della Salute e Della Scienza University-Hospital, Turin, Italy.
  • Baglietto L; Department of Research, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, MI, Italy.
  • English D; Dipartimento di Medicina Clinica e Chirurgia Federico II University, Naples, Italy.
  • Severi G; Hyblean Association for Epidemiological Research AIRE-ONLUS, Ragusa, Italy.
  • Giles GG; MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Milne RL; Italian Institute for Genomic Medicine (IIGM), Turin, Italy.
  • Herceg Z; Department of Clinical and Experimental Medicine, University of Pisa, 56126, Pisa, Italy.
  • Garcia-Closas M; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
  • Flanagan JM; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
  • Southey MC; CESP UMR1018, Paris-Saclay University, UVSQ, Inserm, Gustave Roussy, Villejuif, France.
Breast Cancer Res ; 24(1): 59, 2022 09 06.
Article in En | MEDLINE | ID: mdl-36068634
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.
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Full text: 1 Database: MEDLINE Main subject: Breast Neoplasms Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Female / Humans Language: En Journal: Breast Cancer Res Journal subject: NEOPLASIAS Year: 2022 Type: Article Affiliation country: Australia

Full text: 1 Database: MEDLINE Main subject: Breast Neoplasms Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Female / Humans Language: En Journal: Breast Cancer Res Journal subject: NEOPLASIAS Year: 2022 Type: Article Affiliation country: Australia