Protective Effect of Aspirin Associated with SNP

People with a low-risk single-nucleotide polymorphism (SNP) who regularly take low doses of aspirin cut their colorectal cancer risk by about 50%, according to a study published in December in the Journal of the National Cancer Institute.

Looking at the SNP at locus rs6983267 on chromosome 8q24 in 840 people with colon cancer and nearly 1,700 control subjects, researchers at Harvard Medical School in Boston, MA, and other institutions showed that a low-risk T variant seems to reduce the expression of the MYC oncogene. rs6983267 lies in a possible enhancer domain for MYC, and the authors showed that the T variant reduced binding of TCF7L2, a transcription factor and binding partner of β-catenin, to the enhancer in an aspirin-dependent manner.

Just under half of the general population carries the low-risk T variant, which was associated with at least a 15% lower risk of developing colorectal cancer in the Harvard study, consistent with results from prior, large genome-wide association studies (GWAS). Those with at least one copy of the variant who also regularly took aspirin lowered their risk even more, by about 50% total, the researchers found.

The benefit was shown primarily in a reduction of cancers that overexpressed nuclear β-catenin, a protein in the WNT cell signaling pathway that regulates MYC expression, says lead researcher Andrew Chan, MD, MPH, an associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital in Boston.

“It may be aspirin directly modifying the β-catenin protein or an indirect effect through aspirin's known effect on prostaglandin synthesis,” Chan says.

It's still too early to say that aspirin should be widely used for cancer prevention, he says, but it's possible that future research will confirm such a benefit, particularly for those with this genetic variant.

This study is notable because it provides a mechanism justifying the use of aspirin in cancer prevention, says Patricia Thompson, PhD, program leader for cancer prevention and control at the University of Arizona Cancer Center in Tucson.

It also moves physicians closer to identifying who is most likely to benefit from aspirin's anticancer activity and at what dose, despite its well-known gastrointestinal and bleeding risks, says Thompson, who wrote an editorial accompanying the study. Having a large body of data on aspirin's role in treating and preventing cardiovascular disease should make future research on its role in colorectal cancer easier, she says.

In addition, Thompson says the study confirms the role that GWAS can play in developing cancer treatments.

“This is a reminder that one of the goals of the GWAS is to try to understand how cancer and other complex diseases develop in humans,” she says. “Each step we start to tease apart, we'll get the big picture, so it is worth the investment.”