Increased epigenetic age in normal breast tissue from luminal breast cancer patients.
Level 4 - case-series / case-control
Case-control study comparing normal tissue epigenetic age between breast cancer patients and unaffected controls
PubMed 30157950 · doi:10.1186/s13148-018-0534-8
What was done
DNA methylation profiling was performed using the Illumina HumanMethylation450k BeadChip on 96 normal breast tissue samples from 88 subjects: 35 patients with luminal breast cancer (40 samples from distant non-tumor sites of primary mastectomy specimens) and 53 unaffected controls (25 from the Komen Tissue Bank and 28 from non-cancer-related breast surgeries). Epigenetic age was estimated using a 353-CpG epigenetic clock and evaluated against chronological age, breast cancer status (stratified by age <50 and ≥50 years), and smoking status via multivariate analysis.
What was found
DNA methylation age in normal breast tissue correlated strongly with chronological age (r = 0.712, p < 0.001). Breast cancer patients exhibited significant epigenetic age acceleration in their normal breast tissue compared to unaffected controls (p = 0.002), which remained significant after adjusting for clinical and demographic variables. Smoking was also positively correlated with epigenetic aging in normal breast tissue (p = 0.012).
Why it matters
These findings suggest that accelerated biological aging is present in non-malignant breast tissue of luminal breast cancer patients, supporting the hypothesis that tissue-specific epigenetic aging may be associated with breast cancer development.
Limits
The study is limited by a small sample size (88 subjects) and an observational case-control design that cannot establish whether epigenetic age acceleration preceded or resulted from cancer. Control samples came from two distinct sources (healthy donors vs. non-cancer surgical patients), introducing potential confounding. Absolute effect estimates (years of acceleration) and confidence intervals were not reported in the abstract.
Cited by
- supports Malignant breast tissue in luminal breast cancer exhibits 10 to 15 years of epigenetic age acceleration.