Epigenetic Harmony: Unraveling The Secrets Of DNA Methylation
Methylation-Based Aging In Women Who Do And Do Not Develop Breast Cancer
Intuitively, a change in cell function would suggest that an alteration has occurred in the DNA (gene) sequence. For instance, the job of the BRCA teams is to repair genetic breaks which when present prevents this job from being completed. If there is a mutation in a BRCA gene, mutations in other parts of the genome can create an environment that increases the risk for breast and ovarian cancer. Specifically, a mutation is a change in the actual DNA genetic code or sequence that prevents a gene from doing its predetermined job. Another example might be someone who inherits from his parents the tendency to have blue eyes. The gene for blue eyes is then said to be “expressed”. The gene that causes a giraffe to have a long neck, as opposed to a short neck, is said to be “expressed”. In the case of the giraffe born with a short neck has likely had a mutation in the gene responsible for neck length. This involves a change in parts of the DNA genetic code.
Epigenetics is the study of stable changes in cell function that do not involve alterations in the sequence of DNA (genetic code). Therefore, the DNA genetic code remains the same but there is a change in the function of the cell that does not involve mutations or a change in the code. Epigenetics has begun to take on increasing clinical importance in the last decade. The term epi is a Greek prefix meaning (over, outside of, around, or in addition to the traditional genetic basis of inheritance). Epigenetics most often represent changes that affect the regulation of gene expression that persist throughout cell division. Therefore, there can be relevant alterations to your genome that do not involve mutation of the genetic code (sequence). There are several examples of epigenetic modifications that produce these changes. One is DNA methylation, and the other is called histone modification, which alters how the genes are expressed without changing the DNA sequence. DNA methylation patterns are known to be established and modified in response to environmental factors by a complex interplay of certain DNA enzymes. In studying the DNA of tumors DNA methylation differences are frequently found among different regions of a particular tumor and likely reflects the history of cancer cells and their response to tumor microenvironment.
In a recent study published in the Journal of the National Cancer Institute earlier this year, researchers studied DNA methylation in older women who do not develop breast cancer. The authors noted that breast cancer survivors have an increased incidence of age-related diseases, suggesting some survivors may be experiencing faster biological aging. The study they examined was an offshoot of the Sister Study cohort and consisted of 417 women who enrolled in this study. The researchers then performed DNA methylation studies using blood samples from the sisters taken an average of 7.7 years apart. They then used this data to calculate three epigenetic metrics of biologic aging which has been shown to be important to biologic aging in prior studies. (GrimAgeAccel, PhenoAgeAccel, DunedinPACE). They found that biologic aging is accelerated following a breast cancer diagnosis and treatment and concluded that breast cancer treatment modalities appear to differentially contribute to biologic aging, particularly in this population of women. Furthermore, when the authors compared cancer-free participants to the breast cancer survivors’ group by different combinations of treatments they received, the data suggested that surgery had little association with the biologic aging metrics but that women receiving other treatments, particularly radiation, had an increase in all three biologic aging metrics. After adjusting for chronologic age follow-up time, and self-reported race in the models they continue to find that biologic aging was most pronounced for women who received radiation therapy.
In summary, the authors suggested that women diagnosed and treated for breast cancer experience greater increases in biologic aging than women who remain breast cancer free. As opposed to prior studies done in this area, the authors found that the increases in biologic aging can be detected in years after treatment and that these increases were most strongly associated with a history of radiation therapy.
Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.