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Dartmouth Research Suggests PGx May Play Role In Aspirin's Ability to Prevent Colorectal Cancer

Aspirin may help to prevent colorectal adenomas in patients who carry a particular gene variant, according to results of a preliminary study by Dartmouth Medical School researchers. 
The findings could be noteworthy for pharmacogenomics because colorectal cancer is among the most prevalent malignancies in the world, and because aspirin has been widely used for decades, is widely tolerated, and has an extremely safe profile.
With genotypes and clinical data from 973 patients followed for three years, the investigators confirmed previous research by María Elena Martinez at the Arizona Cancer Center and colleagues showing that variations in the ornithine decarboxylase gene can modulate the effectiveness of aspirin as a preventive agent.
Martinez and colleagues also linked the ODC gene to an increased risk of colorectal adenomas, but the Dartmouth researchers were not able to confirm that finding with significant results.
“If confirmed, this does offer the opportunity for what could be the prediction of very significant effects, so I think the key here is getting the effect confirmed,” John Baron, a co-author of the current study and a professor of medicine at the medical school, told Pharmacogenomics Reporter this week.
The Dartmouth group’s study might be important beyond colorectal preventive treatment with aspirin. Since it is believed that NSAIDs may reduce the risk of colorectal polyps, ODC gene variations may also have implications for other NSAIDs, although the group didn’t study that question, said Baron. Also, “aspirin, in addition to its cardio-protective properties, seems to lower the risk of certainly colorectal neoplasia, but potentially other cancers as well,” he said.
The mechanism of interaction between ODC and aspirin is not understood, said Baron.
Baron said he could not predict whether the study’s results might be pursued to produce a pharmacogenomic method for polyp prevention, especially until the results are validated. Right now, aspirin is not the only preventive measure for colorectal adenomas, he said.
Baron suggested that molecular diagnostics companies and clinical reference laboratories are the most likely to be able capitalize on the research.
The Dartmouth group’s paper, which is published in the Oct. 18 issue of the Journal of the National Cancer Institute, resulted from data coming out of the ongoing Aspirin/Folate Prevention of Large Bowel Polyps trial, which is examining the use of aspirin or folate to prevent the recurrence of adenomas of the large bowel in about 1,121 patients.
Baron is the principal investigator of the Dartmouth-based clinical trial. It is expected to conclude in December 2011.
Baron said Bayer provided aspirin for the clinical trial and Wyeth provided folate. Aspirin has long been available as a generic drug, so there may not be much incentive for Bayer to pursue a special test for directing its pharmacogenomic use.
There is no plan as yet for follow-up studies to confirm the relationship between ODC genotype and aspirin protectiveness, said Baron. “It’s possible that some randomized trials of aspirin in the future will be available to look at some of these issues, but I don’t think that’s going to be productive,” so any efforts by another research team to verify that association will probably entail a less trustworthy observational study, he said. “Because we had a randomized study, we are able to see things that many observational studies can’t.”
Several groups Baron mentioned have ongoing adenoma studies or clinical data and patient DNA that might be useful in following up his team’s study, including Bob Sandler at the University of North Carolina, Robert Hale at the University of Southern California, and John Potter at the University of Washington.

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