Abstract
PurposeAge is one of the strongest risk factors for the development of breast cancer, however, the underlying etiology linking age and breast cancer remains unclear. We have previously observed links between epigenetic aging signatures in breast/tumor tissue and breast cancer risk/prevalence. However, these DNA methylation-based aging biomarkers capture diverse epigenetic phenomena and it is not known to what degree they relate to breast cancer risk, and/or progression.MethodsUsing six epigenetic clocks, we analyzed whether they distinguish normal breast tissue adjacent to tumor (cases) vs normal breast tissue from healthy controls (controls).ResultsThe Levine (p = 0.0037) and Yang clocks (p = 0.023) showed significant epigenetic age acceleration in cases vs controls in breast tissue. We observed that much of the difference between cases and controls is driven by CpGs associated with polycomb-related genes. Thus, we developed a new score utilizing only CpGs associated with polycomb-related genes and demonstrated that it robustly captured epigenetic age acceleration in cases vs controls (p = 0.00012). Finally, we tested whether this same signal could be seen in peripheral blood. We observed no difference in cases vs. controls and no correlation between matched tissue/blood samples, suggesting that peripheral blood is not a good surrogate marker for epigenetic age acceleration.ConclusionsMoving forward, it will be critical for studies to elucidate whether epigenetic age acceleration in breast tissue precedes breast cancer diagnosis and whether methylation changes at CpGs associated with polycomb-related genes can be used to assess the risk of developing breast cancer among unaffected individuals.
Highlights
Outside of genetic mutations in BRCA genes, age is the strongest risk factor for the development of breast cancer
Study specimens Study specimens were used from a previous study [22] which included four cohorts; 1) DNA collected from peripheral blood from breast cancer patients (n = 79) presenting to Yale New Haven Hospital with a new diagnosis of breast cancer who had not received any chemotherapy, radiation, or endocrine therapy prior to surgery, 2) DNA collected from peripheral blood from women without cancer (n = 91) from the Susan G
Patient demographics Normal breast tissue (> 3 cm away from breast tumor) was analyzed from 34 patients with breast cancer and 50 healthy controls, and peripheral blood samples were analyzed from 79 patients with breast cancer and 91 healthy controls
Summary
Outside of genetic mutations in BRCA genes, age is the strongest risk factor for the development of breast cancer. DNAm impacts transcriptional repression/activation and is thought to control a number of cellular properties from differentiation to replication. Both cancer and aging have been associated with specific changes in the pattern of DNAm, often characterized by gains of DNAm at gene promotors and loss of global DNAm, in intergenic regions associated with dispersed retrotransposons, heterochromatic DNA repeats, and endogenous retroviral elements [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
