Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: A pooled analysis of four prospective studies
Year: 2022
Type: preprint
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, 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. 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, estrogen 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 =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. 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.
Source: Research Square
Authors: Pierre-Antoine Dugué, Clara Bodelon, Felicia Chung, Hannah Brewer, Srikant Ambatipudi, Joshua Sampson, Cyrille Cuenin, Véronique Chajès, Isabelle Romieu, Giovanni Fiorito, Carlotta Sacerdote, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Paolo Vineis, Silvia Polidoro, Laura Baglietto, Dallas English, Gianluca Severi, Graham Giles, Roger Milne, Zdenko Herceg, Montserrat Garcia-Closas, James Flanagan, Melissa Southey
Institutions: Monash University, National Cancer Institute, Centre international de recherche sur le cancer, Imperial College London, Sree Chitra Thirunal Institute for Medical Sciences and Technology, University of Sassari, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Fondazione IRCCS Istituto Nazionale dei Tumori, University of Naples Federico II, Associazione Iblea per la Ricerca Epidemiologica E.T.S., Italian institute for Genomic Medicine, University of Pisa, The University of Melbourne, Cancer Council Victoria, Université Paris-Saclay
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Cancer Research UK, National Institute for Health and Care Research, Ovarian Cancer Action, Imperial College London, European Commission, Fondation ARC pour la Recherche sur le Cancer, Institut National Du Cancer, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, NIHR Imperial Biomedical Research Centre, National Cancer Institute
OpenAlex ID: W4280534811