TY - JOUR
T1 - Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer
T2 - a pooled analysis of four prospective studies
AU - Dugué, Pierre Antoine
AU - Bodelon, Clara
AU - Chung, Felicia F.
AU - Brewer, Hannah R.
AU - Ambatipudi, Srikant
AU - Sampson, Joshua N.
AU - Cuenin, Cyrille
AU - Chajès, Veronique
AU - Romieu, Isabelle
AU - Fiorito, Giovanni
AU - Sacerdote, Carlotta
AU - Krogh, Vittorio
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Vineis, Paolo
AU - Polidoro, Silvia
AU - Baglietto, Laura
AU - English, Dallas
AU - Severi, Gianluca
AU - Giles, Graham G.
AU - Milne, Roger L.
AU - Herceg, Zdenko
AU - Garcia-Closas, Montserrat
AU - Flanagan, James M.
AU - Southey, Melissa C.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - Breast cancer risk
KW - DNA methylation
KW - Epigenetic aging
KW - Lifestyle
KW - Prospective study
UR - http://www.scopus.com/inward/record.url?scp=85137312569&partnerID=8YFLogxK
U2 - 10.1186/s13058-022-01554-8
DO - 10.1186/s13058-022-01554-8
M3 - Article
C2 - 36068634
AN - SCOPUS:85137312569
SN - 1465-5411
VL - 24
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 59
ER -