Dugue, Pierre-Antioine and Bodelon, Clara and Chung, Felicia Fei Lei * and Brewer, Hannah R and Ambatipudi, Srikant and Sampson, Joshua N and Cuenin, Cyrille and Chajes, Veronique and Romieu, Isabelle and Fiorito, Giovanni and Sacerdote, Carlotta and Krogh, Vittorio and Panico, Salvatore and Tumino, Rosaria and Vineis, Paolo and Polidoro, Silvia and Baglietto, Laura and English, Dallas and Severi, Gianluca and Giles, Graham G and Milne, Roger L and Herceg, Zdenko and Garcia-Closas, Montserrat and Flanagan, James M and Southey, Melissa C (2022) Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies. Breast Cancer Research, 24. ISSN 1465-542X
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | breast cancer risk; DNA methylation; epigenetic aging; lifestyle; prospective study. |
| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RC Internal medicine |
| Divisions: | Others > Non Sunway Academics Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Department of Medical Sciences |
| Depositing User: | Ms Yong Yee Chan |
| Related URLs: | |
| Date Deposited: | 12 Aug 2024 00:54 |
| Last Modified: | 12 Aug 2024 00:54 |
| URI: | http://eprints.sunway.edu.my/id/eprint/3059 |
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