Aspirin’s Preventive Effect for Colorectal Cancer Linked to Genotype

Aspirin’s preventive effect for colorectal cancer may be limited to tumors without a genetic mutation known as BRAF, according to the results of a study published in the Journal of the American Medical Association.[1]

Colorectal cancer remains the second leading cause of cancer-related death in the United States. About 10 percent of colorectal cancers have a mutated BRAF gene. Studies have shown that BRAF mutations confer a poorer prognosis in colorectal cancer and also may predict a poorer response to targeted agents known as EGFR inhibitors.

Some studies have found a link between daily aspirin and reduced cancer incidence and mortality.[2][3] What’s more, aspirin appears to reduce the risk of hereditary colon cancer.[4] Researchers continue to study the effects of daily aspirin in order to determine its potential as a preventive strategy in colon cancer.

Researchers evaluated data from two large observational studies—the Nurses’ Health Study and the Health Professionals Follow-up Study—to examine the relationship between aspirin use and BRAF tumor status. The two studies combined included data from 128,000 participants—and both studies had follow-up data on cancer incidence through July 2006 and on cancer mortality through 2011. Data in the studies also included tumor genotype status for participants.

During follow-up, there were 1,226 cases of colorectal cancer, of which 182 involved the BRAF mutation. Overall, there was a lower rate of colorectal cancer among the daily aspirin users. What’s more—there appeared to be a dose-response effect: among participants who took two to five aspirin tablets per week, there was only a trend toward reduced cancer risk, whereas among those who took more than 14 tablets per week, the cancer risk was cut by 50 percent.

However, it appears this risk reduction was limited to those without the BRAF mutation. When researchers compared those with wild-type BRAF (no mutation) and those with a BRAF mutation, they found that those with the mutation did not appear to receive the same preventive effect from aspirin.

The researchers concluded that regular daily aspirin use was associated with a lower risk of colorectal cancer without the BRAF mutation, but not with BRAF-mutated colorectal cancer. They speculate that “BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin.”

References


[1] Nishihara R, Lochhead P, Kuchiba A, et al. Aspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status. JAMA. 2013; 309(24): 2563-2571.

[2] Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nature Reviews Clinical Oncology. Published early online April 3, 2012. doi:10.1038/nrclinonc.2011.199

[3] Rothwell PM, Price JF, Fowkes FGR et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits n 51 randomised controlled trials. Lancet. Early online publication March 21, 2012.

[4] Burn J, Gerdes A-M, Macrae F et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. Early online publication October 28, 2011.

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