While non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin and ibuprofen reduce risk for colon and rectal cancer, long-term smokers may not enjoy the benefit. One group of smokers may have no benefit at all.
Researchers at the Fred Hutchinson Cancer Center in Seattle studied 3,300 area adults, half of whom had colon cancer. They found that people who had smoked for more than 20 years and had never used NSAIDS had the highest risk for colon cancer. But smokers who did use NSAIDS regularly had an increased risk for colon cancer that was about 1/3 higher than non-smokers.
In particular, the research team looked at colorectal cancers with microsatellite instability(MSI). Microsatellites instability results from changes in short sequences in DNA which aren’t corrected. Increased numbers of microsatellites can result in some types of colon cancer, often when genes that repair damage are faulty (mismatch repair genes) About 15% to 20% of colon cancers have high levels of microsatellite instability.
Smokers whose cancers were high in microsatellite instability got no benefit at all from NSAID use. Risk for colorectal cancer was as high in NSAID-using smokers as it was in smokers who did not use NSAIDS regularly.
Virginia Chia, who headed the study, believes that it is possible that long-term smoking provides such frequent and consistent assaults on cell DNA that it cannot be reliably repaired, particularly in people who already lack the mismatch repair gene. She wrote,
"This accumulated damage might not be reversible. NSAIDs act to suppress inflammatory processes and may help limit the progression toward cancer. However, people who have microsatellite-unstable tumors may be even more susceptible to the effects of smoking because they already have a reduced capacity to repair DNA, even in the presence of strong anti-inflammatory agents.”
Results of the study appear in the July 1, 2006 issue of Cancer Research.
An article about the study appears on EurekaAlert.
smoking and colorectal cancer microsatellite instability non-steroidal anti-inflammatory drugs
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