Yale Research Reveals “Biologically Older” Tissue in Patients with Breast Cancer

Mariya Rozenblit, MD

An analysis by Yale Cancer Center researchers identified accelerated genetic aging in breast tissue adjacent to breast cancer tumors. Their findings demonstrate that adjacent breast tissue is “biologically older” than the chronologic age of the patient, a discovery that may explain why some women develop breast cancer at younger age and may also become a future marker of breast cancer risk. The findings were recently published in Clinical Epigenetics.

Outside of genetic mutations in BRCA genes, age is the strongest known risk factor for the development of breast cancer. However, it remains unclear why some women develop breast cancer at a young age despite having no mutations in BRCA or any other cancer causing genes.

Using six epigenetic clocks, that measure the biological age of tissues, a research team at Yale Cancer Center analyzed whether they could distinguish normal breast tissue adjacent to tumor versus normal breast tissue from healthy controls. Their analysis showed significant epigenetic age acceleration in tissue adjacent to breast tumors. Further observation showed that much of the age difference is driven by CpGs associated with polycomb-related genes. CpGs are important regions of DNA where methylation can occur and polycomb-related genes code for proteins important in forming chromatin-modifying complexes. These complexes are known to be important in embryonic development but now are increasingly recognized as playing an important role in stem cells and dysregulations found in cancer cells.

“Moving forward, it will be critical for studies to explain whether epigenetic age acceleration in breast tissue precedes the emergence of breast cancer,” said Mariya Rozenblit, MD, assistant professor of medicine (Medical Oncology) at Yale Cancer Center and lead author on the paper. “Our next step is to determine if methylation changes at CpGs associated with polycomb-related genes can be used to assess the risk of developing breast cancer.”

The following Yale authors also contributed to the study: Morgan Levine, Lajos Pusztai, Erin Hofstatter, Tess O’Meara, and Disha Dalela.