A new study shows that people with high levels of the 15-PGDH enzyme who used aspirin regularly were half as likely to be diagnosed with colorectal cancer.
Observation studies have shown that for those who take aspirin regularly, such as for chronic conditions, the chances of being diagnosed with colorectal cancer are less likely. Cohort and case-controlled studies have demonstrated similar results. (See Role of Aspirin in Colorectal Cancer Prevention and Treatment.)
Now, a new study shows that certain people are more likely to benefit from the anti-cancer activity of the over-the-counter pill. In a study published in Science Translational Medicine, researchers demonstrated that those with high levels of the 15-PGDH enzyme who used aspirin regularly were half as likely to be diagnosed with colorectal cancer (hazard ratio [HR] = 0.49). For those individuals who had low levels of the enzyme, regular aspirin use had no impact on colorectal cancer risk (HR = 0.9). The 15-PGDH enzyme is found in the tissue that lines the digestive tract. This is the first study to provide data that explain why it appears that only certain individuals benefit from the chemoprevention activity of aspirin.
“These findings represent a clean yes-no about who would benefit from aspirin,” said senior author Sanford Markowitz, MD, PhD, of Case Western Reserve University School of Medicine in Cleveland, in a statement.
Markowitz, along with Stephen P. Fink, PhD, of the Case Comprehensive Cancer Center at Case Western Reserve University, and colleagues from the Dana-Farber Cancer Institute, Harvard Medical School, and Massachusetts General Hospital in Boston, as well as the Warren Alpert Medical School of Brown University, analyzed data on 127,865 participants from two large nationwide health surveys-the Nurses’ Health Study and the Health Professionals Follow-Up Study. The authors collected data on aspirin use and colon cancer diagnosis every 2 years. Of the participants, there were 270 colon cancer cases that could be assessed for 15-PGDH expression.
The 15-PGDH enzyme has been shown to antagonize prostaglandin-endoperoxide synthase 2 (PTGS2) during oncogenesis. The PTGS2 enzyme is thought to be the main target of aspirin in its chemopreventive role. Markowitz and fellow authors hypothesized that those with different levels of 15-PGDH may respond differently to the anti-proliferative effects of aspirin in the gut. These study results suggested that aspirin works alongside the 15-PGDH enzyme to prevent colorectal tumorigenesis.
Colorectal cancer is the second leading cause of cancer-related deaths and approximately 50,000 people will die from the disease this year in the United States, according to the American Cancer Society. Death rates from the disease have been dropping over the last 20 years as a result of better screening rates, but additional mechanisms for further reducing rates of colorectal cancer are needed. (See Drop in Colon Cancer Rates for Older Americans.)
The researchers are now developing a test to measure 15-PGDH in the gut and organizing a prospective trial to test and confirm the findings in this current retrospective study.
They suggested 15-PGDH levels in the colon could be a screening biomarker, measured during a routine colonoscopy, to predict whether a patient could benefit from the chemoprevention activity of aspirin. “During a colonoscopy, a gastroenterologist could easily and safely take an additional biopsy from the colon in individuals for whom preventive aspirin treatment might be appropriate,” said senior author Andrew Chan, MD, of the Brigham and Women’s Hospital and Harvard Medical School, in a statement.
The study was partly funded by the Entertainment Industry Foundation’s National Colorectal Cancer Research Alliance (NCCRA).