Aspirin improves colorectal cancer survival in tandem with gene mutation

Aspirin significantly improves survival in colorectal cancer patients who have a mutation in a carcinogenesis-associated signaling pathway, the results of a US and Japanese study indicate.

"This relationship appeared to be independent of aspirin use before diagnosis," note Shuji Ogino, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and colleagues.

The team adds that the mutation, in the PIK3CA (phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit alpha polypeptide) gene, may serve as a tumor biomarker that predicts the response to the initiation of aspirin therapy in patients with newly diagnosed colorectal cancer.

Ogino and team note that aspirin is known to downregulate phosphatidylinositol 3-kinase signaling activity, and that this could underlie the association between colorectal cancer survival and aspirin therapy.

In an accompanying editorial in the New England Journal of Medicine, Boris Pasche, from the University of Alabama at Birmingham, USA, says: "Since more than one of six primary colorectal cancers harbors PIK3CA mutations, targeted use of adjuvant aspirin could have a major effect on the treatment of colorectal cancer."

The team examined data on 964 patients with rectal or colon cancer enrolled in the Nurses' Health Study and the Health Professionals Follow-up Study.

In all, 17% of patients had tumors with PIK3CA mutation among aspirin users and non-users. Over a median follow-up of 153 months, there was a total of 395 deaths, of which 190 were due to colorectal cancer.

Among patients with the PIK3CA mutation, regular aspirin use following cancer diagnosis was associated with significantly longer cancer-specific survival, at a multivariate hazard ratio for cancer-related death of 0.18 compared with those who did not regularly use aspirin. In contrast, aspirin use was not associated with cancer-specific survival among patients with wild-type PIK3CA tumors, at a hazard ratio of 0.96. A similar pattern was seen for overall survival.

Furthermore, among patients with PIK3CA mutation tumors, 3% of those who used aspirin regularly died from colorectal cancer within 5 years of diagnosis, compared with 26% of those who did not use aspirin. For patients with wild-type PIK3CA tumors, the 5-year cumulative cancer-specific mortality rate was the same in both aspirin users and non-users, at 15%.

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