The well-documented protective effect that aspirin and nonsteroidal anti-inflammatory drugs exert against colon cancer has been linked to three genetic variations at chromosome 12 and 15, according to a report published online March 17 in JAMA.
In a genome-wide investigation of the interrelationship between genetic markers and the regular use of aspirin/NSAIDs, researchers found that the drugs were differentially associated with colorectal cancer risk according to variations at single-nucleotide polymorphisms (SNPs) on chromosome 12p12.3 (rs2965667 and rs10505806) and chromosome 15q25.2 (rs16973225).
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These findings “can help to identify population subgroups defined by genetic background that may preferentially benefit from chemopreventive use of these agents and offer novel insights into underlying mechanisms of carcinogenesis,” said Dr. Hongmei Nan of the department of epidemiology at Indiana University and the Bren Simon Cancer Center, both in Indianapolis, and her associates.
To obtain a large population for the genome-wide study, the investigators pooled data from 10 observational studies conducted between 1976 and 2003 in Australia, Canada, Germany, and the United States, which enrolled 8,634 colon cancer cases and 8,553 control subjects matched for age, sex, and race/ethnicity.
Compared with nonuse of aspirin, NSAIDs, or both, regular use was associated with a lower risk of colorectal cancer: The overall prevalence of the disease was 28% among regular users, compared with 38% among nonusers, for an odds ratio of 0.69. The regular use of aspirin alone also was associated with a lower risk of colorectal cancer: The prevalence was 24% among regular users and 31% among nonusers, for an odds ratio of 0.71.
This protective effect, however, and thus an NSAID user’s risk for colorectal cancer, varied by whether patients carried the genetic variants and how many copies of the risk alleles they carried, Dr. Nan and her associates said (JAMA 2015;313:1133-42).All three genetic variants are located near genes known to be involved in the pathogenesis of colon cancer, including genes that regulate the production of proinflammatory prostaglandins and interleukins, particularly within the gut. This proximity supports the idea that aspirin and NSAIDs exert their gut-protective effects through these inflammatory mediators, the investigators said.
The National Cancer Institute and the National Institutes of Health supported the study. Dr. Nan reported having no financial disclosures. One of her associates reported holding a patent for aspirin as a colorectal chemopreventive agent and two others reported ties to Arctic Dx, Bayer Healthcare, Pfizer, and Pozen.