Study: Genetic variants determine whether aspirin/NSAIDS will reduce colorectal cancer risk

Regular use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) appears to reduce the risk of colorectal cancer in most individuals, but a few individuals with rare genetic variants do not share this benefit, according to a study published in the March 17 issue of JAMA.

Andrew Chan, MD, MPH, of the Massachusetts General Hospital (MGH) Gastroenterology Division, co-senior and co-corresponding author, and colleagues, analyzed data from the Colon Cancer Family Registry and from 9 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium, which includes the Nurses’ Health Study, the Health Professionals Follow-up Study and the Women’s Health Initiative.

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They compared genetic data for 8,624 individuals who developed colorectal cancer with that of 8,553 individuals who did not, matched for factors such as age and gender. The comprehensive information on lifestyle and general health data provided by participants in the studies again confirmed that regular use of aspirin or NSAIDs was associated with a 30% reduction in colorectal cancer risk for most individuals. However, that preventive benefit did not apply to everyone, and the study found no risk reduction in participants with relatively uncommon variants in genes on chromosome 12 and chromosome 15.

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Additional questions need to be answered before preventive treatment with these medications can be recommended for anyone, the study authors noted.

Dr Chan“Many studies, including randomized trials, have demonstrated that NSAIDS, particularly aspirin, protect against colorectal cancer,” said Dr Chan. “However, these medications are known to have serious side effects-especially gastrointestinal bleeding.”

Therefore, determining whether certain subsets of the population might not benefit from aspirin use for the purpose of cancer prevention may allow for better personalized recommendations.

“We found that an individual's genetic background may predict whether he or she might benefit from aspirin for prevention,” Dr Chan told FormularyWatch. “These findings may allow us to target specific individuals, defined by their genetic profile, for aspirin chemoprevention. In addition, we found that the variation in genes that influence benefit were associated with biologically plausible pathways. Thus, these results illuminate potential molecular targets for novel chemopreventive agents.”

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Although it is premature to recommend genetic screening to guide clinical care, Dr Chan said that the findings do provide proof-of-principle for a precision medicine strategy for prevention and highlight the need to validate results in other populations.