Epigenetic changes with age in normal breast tissue are linked to cancer-related changes

A recent study published in Breast Cancer Research provides a novel insight into how changes that occur with age may predispose breast tissue cells to becoming cancerous. The team identified age as the risk factor most strongly associated with normal breast DNA methylation differences and; regions in the genome where DNA methylation changes occur with age are particularly sensitive to disruption in cancer. In conclusion, this novel data provides insight into how epigenetic dysregulation with age in normal breast tissue, contributes to breast cancer risk.

Increasing age, alcohol intake, being overweight following menopause and family history are all factors known to be associated with a higher risk of breast cancer.  Unfortunately, the underlying biological mechanisms through which these factors contribute to onset of disease remains unclear.

“Our group and others have previously shown that epigenetic modifications such as DNA methylation are early events in breast carcinogenesis,” commented lead author, Brock Christensen (Dartmouth Geisel School of Medicine, NH, USA). “In this work, we measured DNA methylation in normal breast tissue samples from disease-free women to investigate whether changes in DNA methylation underlie the biologic effects of known breast cancer risk factors.”

The recent study differs from previous work by characterizing molecular differences in healthy normal tissues that are associated with cancer risk factors. “Previous studies have examined DNA methylation patterns in populations with invasive breast cancer and we have examined epigenetic profiles of pre-invasive (early stage) breast cancers,” explained Christensen. “However, this work focused on normal breast tissue donated by disease-free subjects who provided robust risk factor data, allowing us to investigate genome-scale DNA methylation in healthy tissue from subjects across a wide range of ages.”

The team demonstrated that DNA methylation changes occur at regulatory regions. Interestingly, the methylation is further exacerbated in cancer, suggesting that age influences breast cancer risk through its contribution to epigenetic dysregulation.

The researchers highlight the importance of future studies aimed at better understanding the mechanisms of these newly identified epigenetic changes. “Ideally, a larger prospective study of normal breast tissue would increase our ability to identify those women at the greatest risk of breast cancer,” concluded Christensen. “Given the challenges of procuring breast tissue and risk factor data, we’re pursuing studies of DNA from cells in breast milk as it’s a tissue-specific specimen, can be obtained without invasive procedures, and is available during a critical window that shapes both short- and long-term risk of breast cancer.”

Sources: Johnson KC, Houseman EA, King JE, Christensen BC. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age. Breast Cancer Research doi.org/10.1186/s13058-017-0873-y 19(1) 81 (2017); Eurekalert release