Genetic Variations May Impact Who Benefits from Aspirin, NSAIDs for CRC Prevention

Ulrike “Riki” Peters, PhD, MPH

Based on results from a new study, researchers now have a better understanding about the mechanisms behind the link between aspirin, NSAIDs, and colorectal cancer prevention.

The study, published in The Journal of the American Medical Association, found that the preventive benefit of aspirin and NSAIDS may be linked to variations in an individual’s DNA.

“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,” Ulrike “Riki” Peters, PhD, MPH, said in a statement.

“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.”

Peters and colleagues analyzed data from 10 large population-based studies based in North America, Australia, and Germany and compared genetic and lifestyle data from 8624 people who developed colorectal cancer and 8553 people who did not. Peters is co-senior author of the paper and a cancer prevention researcher in the Public Health Sciences Division at Fred Hutchinson Cancer Research Center in Seattle.

The study found that while regular use of aspirin and NSAIDs was associated with an overall reduction in the risk of colorectal cancer, there was no protective effect among about 9% of the participants who had genetic variations on chromosome 15.

By looking at genetic variations, researchers found that about 4% of the participants who carried genotypes on chromosome 12 had an increased risk of colorectal cancer.

Researchers hope that by better understanding the interplay between genetic variations and the use of aspirin and NSAIDS, they will be able to identify which patients should take those medications for cancer prevention and who shouldn’t.

“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,” Peters said. “But we’re not there yet.”

Co-corresponding author and lead biostatistician Li Hsu, PhD, also of Fred Hutch, said a larger follow-up study is planned.

“We would certainly like to validate the results . . . and truly see whether we can understand the biological mechanisms of these gene-by-environment interactions,” Hsu said in a statement. “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.”

“There’s a long way between our finding and a public health impact, but that’s the reason why we study the gene-by-environment interaction,” Hsu added.