Breast Cancer Research (Sep 2022)

Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies

  • 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

DOI
https://doi.org/10.1186/s13058-022-01554-8
Journal volume & issue
Vol. 24, no. 1
pp. 1 – 9

Abstract

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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.

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