"We had found that increased fatigue was similar no matter whether patients received chemotherapy before or after surgery," Torres says, "indicating that the timing of chemotherapy was less important than whether you got it in the first place."
In the current study, all the women went through partial mastectomy surgery. Some received varying forms of chemotherapy, and all received radiation at the end. They found that women who had been treated with chemotherapy exhibited changes in the methylation of the DNA in their white blood cells. Some of these changes were still present six months after radiation.
Methylation is an epigenetic alteration in DNA, which does not change the A/C/G/T "letter" information in the DNA but does change how that information is read by the cell, influencing whether a gene is turned on or off.
The researchers scanned hundreds of thousands of potential sites of methylation; only eight sites were reliably altered in women who received chemotherapy, and changes at half of those sites were visible six months later.
The biology connecting this handful of sites to inflammation remains unclear; the eight sites were not in genes that encode inflammatory signaling proteins secreted into the blood, for example. However, the methylation changes did correlate with increased levels of two inflammatory signaling proteins, IL-6 and sTNFR2, that have been associated with fatigue in breast cancer survivors.
Many chemotherapeutic agents are effective precisely because they damage DNA in cancer cells. While it was well known that chemotherapy induces epigenetic changes in cancer cells, this is the first study to identify epigenetic changes induced by chemotherapy in non-cancerous cells of the blood.
The authors hypothesize that chemotherapy may directly alter methylation stat
|Contact: Quinn Eastman|
Emory Health Sciences