The humble aspirin may have just added another beneficial effect beyond its ability to ameliorate headaches and reduce the risk of heart attacks: it lowers risk for colon cancer among people with high levels of a specific type of gene.
The extraordinary finding comes from a multi-institutional team that analyzed data and other material from two long-term studies involving nearly 128,000 participants. The researchers found that people whose colon has high levels of a specific gene product, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) RNA, dramatically reduce their chances of developing colorectal cancer by taking aspirin. In contrast, aspirin provides no benefit to people whose colon shows low levels of 15-PGDH.
The findings appeared in Science Translational Medicine (2014; doi:10.1126/scitranslmed.3008481). Previous trials and prospective studies had indicated that aspirin could reduce colorectal cancer risk, but this retrospective study provides the first evidence to help explain why aspirin benefits some people, but not others.
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“If you looked at the folks from the study who had high 15-PGDH levels and took aspirin, they cut their risk of colon cancer by half,” said senior author Sanford Markowitz, MD, PhD, Ingalls Professor of Cancer Genetics at Case Western Reserve School of Medicine in Cleveland, Ohio. “If you looked at the folks from the study that were low for 15-PGDH, they did not benefit at all from taking aspirin. These findings represent a clean Yes-No about who would benefit from aspirin.”
In this latest effort, the scientists sought to build on earlier research that indicated that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, reduces the chances of developing colon cancer for some persons, but not in all. Their question: Why? What is different between those helped by aspirin, and those who saw no effects? The scientists sought to develop a test that would help guide physicians and patients in determining whether an aspirin regimen would be of benefit.
The team examined tissues from 270 colon cancer patients culled from 127,865 participants followed for more than three decades in the Harvard-based Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Previous reports from the Massachusetts General/Dana-Farber team indicated that participants in these studies who regularly took aspirin had a lower risk of colorectal cancer.
In this latest study, the investigators combined forces in a much larger study to examine whether 15-PGDH levels might also be associated with the colon cancer-preventing benefits of aspirin. Normal colon tissue was dissected from the pathology specimens of NHS/HPFS participants who developed colon cancer over the studies’ follow-up period. These colon tissues were analyzed to identify which among them had high or low levels of colon 15-PGDH.
The study is among the first examples of the type of test that could allow more personalized decisions about treatment to prevent colorectal cancer. It also allows those whose 15-PGDH levels indicate aspirin would have little impact to avoid the potential gastrointestinal challenges, such as stomach ulcers, that can accompany aspirin use.