학술논문
Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies
Document Type
article
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
Source
Breast Cancer Research, Vol 24, Iss 1, Pp 1-9 (2022)
Subject
Language
English
ISSN
1465-542X
Abstract
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.