Navigation Links
Imprint of chemotherapy linked to inflammation in breast cancer survivors
Date:3/4/2014

Many breast cancer survivors experience fatigue and other debilitating symptoms that persist months to years after their course of treatment has ended.

Now researchers at the Winship Cancer Institute of Emory University have found clues that may explain how these symptoms can linger. Chemotherapy, one of the major treatments for breast cancer, can leave a long-lasting epigenetic imprint in the DNA of breast cancer patients' blood cells. That imprint is associated with biological signs of inflammation up to six months after the completion of treatment. Inflammation in turn is believed to cause symptoms like fatigue.

The findings are now published online in the journal Brain, Behavior and Immunity.

"Chemotherapy is a life-saving intervention, but for some women it comes at a cost," says Mylin Torres, MD, assistant professor of radiation oncology at Emory University School of Medicine and Winship Cancer Institute. "These results are the first to suggest a biological mechanism by which treatment-related side effects can persist long after treatment completion in women with breast cancer."

That achy, tired feeling that comes from the flu is caused by inflammation, the body's natural response to infection or a wound but it usually disappears once an illness is over. In patients being treated for cancer, fatigue has also been linked to inflammation and up to 30 percent of breast cancer survivors experience persistent fatigue long after treatment has ended.

To investigate the biology behind persistent cancer-related inflammation, Torres teamed up with Andrew Miller, MD, professor of psychiatry and behavioral sciences and director of psychiatric oncology at Winship Cancer Institute. First co-authors of the paper are Alicia Smith, PhD, assistant professor of psychiatry and behavioral sciences, and Karen Conneely, PhD, assistant professor of human genetics.

In a previously published study led by Torres and Miller, chemotherapy was associated with increased markers of inflammation in the blood which correlated with fatigue.

"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 status in the blood cells, or it may be a result of the inflammatory response to chemotherapy-related tissue injury.

"It may be something about the intensity or the repetitive nature of chemotherapy that makes it qualitatively different from acute inflammation," Miller says. "The more we know about this imprinting process, the better chance we have of getting to new therapies for chronic treatment-related problems, such as fatigue, in breast cancer survivors."


'/>"/>
Contact: Quinn Eastman
qeastma@emory.edu
404-727-7829
Emory Health Sciences
Source:Eurekalert

Related medicine news :

1. Study identifies protein that helps developing germ cells wipe genes clean of past imprints
2. Chemotherapy proves life-saving for some leukemia patients who fail induction therapy
3. Adding drug to standard chemotherapy provides no survival benefit for older lung cancer patients
4. Genetic predictor of breast cancer response to chemotherapy
5. Chemotherapys effect on overall survival seems to increase based on tumor size
6. Accelerated chemotherapy given before surgery benefits patients with muscle-invasive bladder cancer
7. Breast MRI helps predict chemotherapys effectiveness
8. Why chemotherapy fails
9. Overexpression of proteins 14-3-3 related to chemotherapy resistance
10. Chemotherapy effective for patients with resected SCLC or large-cell neuroendocrine carcinoma
11. Pediatric regime of chemotherapy proves more effective for young adults
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... TX (PRWEB) , ... June 25, 2016 , ... ... the United States, named Dr. Sesan Ogunleye, as the Medical Director of its new ... the facility Medical Director of our new Mesquite location,” said Dr. James M. Muzzarelli, ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... Conventional wisdom ... of success. In terms of the latter, setting the bar too high can result ... more than just slow progress toward their goal. , Research from PsychTests.com ...
(Date:6/24/2016)... ... June 24, 2016 , ... Marcy was in a crisis. Her son James, eight, was out ... family verbally and physically. , “When something upset him, he couldn’t control his emotions,” remembers ... would throw rocks at my other children and say he was going to kill them. ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Comfort Keepers® ... American Cancer Society and the Road To Recovery® program to drive cancer patients to ... and other adults to ensure the highest quality of life and ongoing independence. ...
(Date:6/24/2016)... ... June 24, 2016 , ... The ... recognize Dr. Barry M. Weintraub as a prominent plastic surgeon and the network’s ... the world, and the most handsome men, look naturally attractive. Plastic surgery should ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  Collagen Matrix, Inc., ... development and manufacturing of collagen and mineral based ... today that Bill Messer has joined ... to further leverage the growing portfolio of oral ... Bill joins the Collagen Matrix executive ...
(Date:6/24/2016)... The Academy of Managed Care Pharmacy (AMCP) ... would allow biopharmaceutical companies to more easily share health ... and coverage decisions, a move that addresses the growing ... The recommendations address restrictions in the sharing of ... label, a prohibition that hinders decision makers from accessing ...
(Date:6/24/2016)...   Pulmatrix, Inc ., (NASDAQ: PULM ... announced today that it was added to the Russell ... comprehensive set of U.S. and global equity indexes on ... milestone for Pulmatrix," said Chief Executive Officer Robert ... progress in developing drugs for crucial unmet medical needs, ...
Breaking Medicine Technology: