PIK3CA mutation identifies colorectal cancer patients who live longer with aspirin
A link between aspirin use after diagnosis of colorectal cancer, gene mutation, and survival
- Date : 26 Oct 2012
- Topic : Gastrointestinal cancers
In a study involving more than 900 patients with colorectal cancer, the researchers found that, for patients whose tumours harboured a mutation in the gene PIK3CA, aspirin use extended survival: five years after diagnosis, 97% of those taking aspirin were still alive, compared to 74% of those not using aspirin. By contrast, aspirin had no impact on five-year survival rates among patients without a PIK3CA mutation. The results were reported in the October 25 issue of the New England Journal of Medicine.
The study's senior author, Shuji Ogino, MD, PhD, of Dana-Farber, Brigham and Women's Hospital, and the Harvard School of Public Health cautioned that the results need to be replicated by other researchers before they can be considered definitive.
Molecular pathology epidemiology study
In the past a regular use of aspirin after diagnosis of colon cancer has been associated with a better clinical outcome. The new finding suggests that the survival benefit is limited to the 20% whose tumours have the PIK3CA mutation. For the remaining patients, aspirin may still be used, but it is likely to be much less effective and can sometimes lead to gastrointestinal ulcers and stomach bleeding.
The study was prompted by previous research that suggested that aspirin blocks an enzyme prostaglandin-endoperoxide synthase 2 (PTGS2) (also known as cyclooxygenase-2), causing a slowdown in the signaling activity of another enzyme, PI3K. That led researchers to hypothesize that aspirin could be especially effective against colorectal cancers in which the PIK3CA gene – which provides a subunit of PI3K – is mutated.
To conduct the study, investigators obtained data on 964 patients with rectal or colon cancer from the Nurses' Health Study and the Health Professionals Follow-up Study – long-term tracking studies of the health of tens of thousands of people. The data included information on the patients' use of aspirin after diagnosis and the presence or absence of PIK3CA mutations in their tumour tissue. The researchers examined tumour markers, including PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and methylation of long interspersed nucleotide element 1.
The study, which combines the study of disease-related genes and research into large populations of individuals, represents a new field, which the authors have termed molecular pathology epidemiology. The field may help to bring together information from two frontiers of cancer research, at both the molecular and population levels.
The authors concluded that findings from this molecular pathological epidemiology study suggest that the PIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy.
The study was supported in part by grants from the USA National Institutes of Health (P01 CA87969, P01 CA55075, P50 CA127003, R01 CA149222, R01 CA137178, and R01 CA151993); the Bennett Family Fund for Targeted Therapies Research; the Entertainment Industry Foundation through the National Colorectal Cancer Research Alliance; the Frank Knox Memorial Fellowship at Harvard University; and a Damon Runyon Clinical Investigator Award.
The following two groups of authors contributed equally to the article: Drs. Liao, Lochhead, and Nishihara and Drs. Fuchs, Chan, and Ogino. They thanked the participants and staff of the Nurses' Health Study and the Health Professionals Follow-up Study for their contributions and the participating cancer registries for their help.
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