Aspirin May Fight Cancer by Suppressing DNA Damage

Aspirin is known to lower risk for some cancers, and a new study points to a possible reason with the finding that aspirin inhibits the accumulation of DNA mutations in abnormal cells in at least one precancerous disorder.

“Aspirin and other nonsteroidal anti-inflammatory drugs, which are commonly available and cost-effective medications, may exert cancer-preventing effects by lowering mutation rates,” said Carlo Maley, PhD, a member of the University of California, San Francisco (UCSF; USA) Helen Diller Family Comprehensive Cancer Center, and an expert on how cancers evolve in the body over time.

In the study, published June 13, 2013, in the online journal PLOS Genetics, Dr. Maley, working with gastroenterologist and geneticist Brian Reid, MD, PhD, of the Fred Hutchinson Cancer Research Center (Seattle, WA, USA), examined biopsy samples from 13 patients with a precancerous condition called Barrett’s esophagus who were monitored for six to 19 years. In an “observational crossover” study design, some patients started out taking daily aspirin for several years, and then stopped, while others started taking aspirin for the first time during observation. The goal was to track the rate of mutations in tissues sampled at different times.

The researchers found that biopsies taken while patients were on an aspirin had on average accumulated new mutations about 10 times more slowly than biopsies obtained during years when patients were not taking aspirin. “This is the first study to measure genome-wide mutation rates of a premalignant tissue within patients for more than a decade, and the first to evaluate how aspirin affects those rates,” Dr. Dr. Maley said.

Ethnic distribution and gender of study patients reflected the known demographics of esophageal cancer, which mostly affects, white, middle-aged, and elderly men, he said. Barrett’s esophagus only occasionally progresses to esophageal cancer.

Tumors are known to accumulate mutations over time much more rapidly than normal tissue, and different mutations arise in different groups of cells within the same tumor. The acquisition of key mutations ultimately allows tumor cells to grow out of control, and diversity within a tumor may foster drug resistance, a phenomenon that is a major focus of Dr. Maley’s research.

Dr. Maley plans to evaluate a hypothesis that may clarify the findings that aspirin’s lowering of mutation rates is due to the agent’s effect of reducing inflammation. Inflammation, a response of the immune system, recently has been known as a key characteristic of cancer. Dr. Maley reported that less inflammation may result in less production within precancerous tissue of oxidants known to damage DNA, and may dampen growth-stimulating signaling.

For the length of the study, the rate of accumulation of mutations measured in the biopsied tissue between time points was slow, even when patients were not taking aspirin, with the exception of one patient. Whereas mutations accumulated at a steady rate, most of the mutations arose before the abnormal tissue was first detected in the clinic, the researchers concluded.

These findings are consistent with the fact that although Barrett's esophagus is a significant risk factor for esophageal cancer, the vast majority of cases do not progress to cancer, according to Dr. Maley. In the one patient who later went on to develop cancer, a population of cellular “clones” with a great number of mutations emerged shortly before he started taking aspirin.

More research is needed to additionally examine the relationship between nonsteroidal mutation rates, anti-inflammatory drugs, and the development of invasive cancer, Sr. Maley stressed. He plans to continue studying Barrett’s esophagus and esophageal cancer, and to expand his research to investigate lung cancer.

Instead of attempting to eradicate the most tumor cells, it may be advantageous to try to block or slow growth and mutation. Current drug treatments for cancer may in many instances hasten the emergence of cancer that is more difficult to eradicate, according to Dr. Maley. The capability to mutate frequently allows tumors to become resistant to drug treatment, he said. A better-adapted mutant can start to create a population of genetic clones that survives and grows, while inadequately adapted tumor cells die off.

Related Links:
University of California, San Francisco
Fred Hutchinson Cancer Research Center