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UCLA study connects types of cancer treatment to reduced cognitive functioning

By Raymond Le

Dec. 2, 2018 11:09 p.m.

UCLA researchers found chemotherapy and other radiation cancer treatments may be linked to worsened cognitive performance.

The study, published this week, showed DNA damage from radiation therapies was associated with worsened cognitive performance in patients.

Patricia Ganz, a health policy and management professor, said chemotherapy and radiation treatments kill cancer cells, as well as normal cells, by damaging the telomerase in DNA, causing cells to die from unsuccessful division. Telomerase is an enzyme that helps repair chromosomes during cell division, and their reduced levels in patients undergoing such treatments suggest that cells are more likely to die.

“When cells are dying, there is more inflammation in the body, and this in turn can affect cognitive function,” Ganz said.

Robert Schiestl, a pathology and environmental health sciences professor, said lower telomerase activity leads to DNA damage because erosion of the ends destabilizes the chromosomes. However, Schiestl states that it is still not understood why lowered telomerase activity yields DNA damage three to six years after the radiation or chemotherapy.

“It is probably similar to other studies showing delayed reproductive effects of chemicals and radiation which we have published before. We also found an increase in inflammation,” Schiestl said. “It is novel and not understood why this results in cognitive decline.”

The study looked at 94 women who had completed three to six years of breast cancer treatment with chemotherapy or radiation and had participated in a previous study that linked DNA damage to radiation treatment.

Judith Carroll, an assistant professor of psychiatry, said the researchers were interested specifically in the explanation as to why lasting symptoms were experienced by some breast cancer survivors and not others.

“The long term or lasting impact of the treatments is of growing concern, as many survivors have changes to quality of life, with increased pain, fatigue and complaints in cognitive function,” Carroll said. “These secondary health effects of the treatments experienced by a proportion of survivors are of concern to the patients and their doctors.”

Investigators used neuropsychological tests and self-reporting to measure cognitive functions. They used blood samples to measure telomerase and DNA damage.

“We then take the blood and isolate the white blood cells from the red blood cells, platelets and plasma. These cells were then split — one set was used to measure telomerase and the other to look at DNA damage,” Carroll said. “We use an assay called the telomere repeat amplification protocol to measure how effective the telomerase from these cells are at extending the telomere.”

Carroll said that DNA damage was assessed using the Comet assay. The assay is a single-cell gel electrophoresis that places cells in a gel and then runs an electrical current through the gel, which moves the broken DNA out of the cell. The more DNA damage that is in the cell, the more DNA that leaves the cell during this process. The researchers then stain the DNA and image it.

“You’ll see that those cells with more DNA damage will have what looks like a comet tail – this is the damaged DNA,” Carroll said. “Cells that remained intact with no tail have very little DNA damage. Each sample has around 100 cells scored by software to create an average amount of DNA damage per person.”

Ganz said that there has only been one other study that has looked at DNA damage in breast cancer survivors and linked it to poorer cognitive function.

“We think this is the first study to look at telomerase,” Ganz said. “All these associations are also common in people as they get older, and we think that cancer treatments may be accelerating the aging process and be leading to some of the cognitive difficulties also seen in normal aging.”

The focus of future research will be in biological aging pathways. Carroll said that biological aging is thought to be involved in many of the symptoms and diseases seen with increasing age, and these occur earlier in some individuals than others.

“By understanding this, we can then develop specific interventions that target these mechanisms,” Carroll said. “For example, if (aging) cells turn out to play a critical role in cognitive decline, then drugs that specifically target this cell type could greatly improve cognitive function.”

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Raymond Le
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