DNA Variations Dictate Preventive Effect of Aspirin on Colorectal Cancer

Genetic variations on chromosome 15 dictate impact of NSAIDs.

The prophylactic effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer prevention differs according to DNA variations, a study published March 17, 2015 in JAMA indicates.

While the link between these drugs and colon cancer prevention has long been established, the mechanisms behind this effect have been unclear. Also if issue in recommending this treatment are the potential harm NSAIDs can cause.

"We've known for a very long time that aspirin, ibuprofen, and other NSAIDs are protective for colorectal cancer, but they can't be used as a preventive agent because of the uncertainty of the risk-benefit ratio -- longtime use can lead to gastrointestinal bleeding and other side effects," study co-senior author Ulrike Peters, PhD, MPH, said in a press release. "We wanted to investigate if genetic variation determined who is responding particularly well with aspirin -- for whom aspirin and NSAID use has particular benefit and for whom it doesn't."

The researchers examined data from 10 large population-based studies in North America, Australia, and Germany to compare genetic and lifestyle information for 8624 colorectal cancer patients with 8553 people who did not develop the disease. Regular use of NSAIDS was linked with an overall reduced risk of colorectal cancer, however, investigators found no prophylactic effect in approximately 9% of participants who had genetic variations on chromosome 15.

Additionally, nearly 4% of participants with 2 rare genotypes on chromosome 12 carried an increased colorectal cancer risk. The interaction between genetic variations and NSAID use, called "gene-by-environment interactions," may help pinpoint patients who could derive the greatest cancer prevention benefit from these medications and which people should avoid using them.

"Our hope is that we can find a subgroup of the population where the benefits so outweigh the risks that it makes sense to take aspirin or NSAIDs," Dr. Peters said. "But we're not there yet."

The researchers indicated plans for a future follow-up study within the next several years to determine if the results of the study can be replicated.

"We would certainly like to validate the results … and truly see whether we can understand the biological mechanisms of these gene-by-environment interactions," lead biostatistician Li Hsu, PhD, said in a press release. "If it does hold true, it will have tremendous impact as to which subset of the group would benefit from using NSAIDs to reduce their [colorectal cancer] risk and in which group it may be harmful if they take NSAIDs.”