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Genetic markers may help determine who benefits from aspirin, NSAIDs in lowering colorectal cancer risk

  • March 17, 2015

INDIANAPOLIS – An Indiana University cancer researcher and her colleagues have identified genetic markers that may help determine who benefits from regular use of aspirin and other nonsteroidal anti-inflammatory drugs for lowering one’s risk of developing colorectal cancer.

Previous studies have shown that regular use of aspirin and NSAIDs lower one’s risk of colorectal cancer, but their use is not recommended as a way to prevent the disease because of uncertainty about the risks and benefits. Thus, the researchers set out to examine the interrelationship between genetic markers and the use of aspirin and NSAIDs to learn who actually benefits from their use. They did so by conducting a genome-wide analysis of gene by environment interactions.

Hongmei Nan, M.D., Ph.D., research associate professor in the Department of Epidemiology at the Richard M. Fairbanks School of Public Health at IUPUI and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, and her colleagues found that colorectal cancer risk differed according to genetic variation at two single nucleotide polymorphisms -- more commonly known as SNPs -- at chromosomes 12 and 15. Interestingly, for the SNP at chromosome 12, they found that aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with a specific genotype, while a higher risk was found among those with other genotypes.

Their study was published March 17 in the Journal of the American Medical Association.

“These novel findings have substantial clinical significance,” Dr. Nan, the lead author, said. “Our findings, if validated in additional populations, may facilitate targeted colorectal cancer prevention strategies and contribute to precision medicine.”

This study is the first and largest genome-wide analysis of gene by environment interactions between SNPs and regular use of aspirin or NSAIDs in relation to colorectal cancer risk. In this case-control study using the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium, the authors included 8,634 colorectal cancer cases and 8,553 non-cancerous controls.

Colorectal cancer is the second leading cause of cancer death in the United States, according to the National Cancer Institute. In 2014, it was estimated that there would be 136,830 new cases of colorectal cancer and an estimated 50,310 people would die from the disease.

Collaborators included Ulrike Peters, Ph.D., M.P.H., and Li Hsu, Ph.D., both of the Fred Hutchinson Cancer Research Center; and Andrew Chan, M.D., M.P.H., of the Massachusetts General Hospital.

This study was supported, in part, by the National Institutes of Health under grant numbers CA137088, CA059045, CA122839, CA097735, CA074783, CA074794, CA48998, CA055075, CA167552, CA137178, CA151993, CA127003, DK098311, CA074783, CA076366, and CA154337.

Hongmei Nan, M.D., Ph.D.

Hongmei Nan, M.D., Ph.D.

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Michael Schug