NSAIDs may not reduce the risk of colorectal cancer in long-term smokers

People who have microsatellite-unstable tumors may be even more susceptible to the effects of smoking.

Issue: August 1, 2006

Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of colorectal cancer by as much as 40%, but this protective effect may not extend to long-term smokers, who already face an increased risk of the disease, according to a recent study.

In a large, population-based study comparing risk factors in people with and without colorectal cancer, researchers from the Fred Hutchinson Cancer Research Center found the highest risk of colon cancer to be among long-term smokers aged 20 years or more who had never used NSAIDs.

The researchers also found that smokers who used NSAIDs still had an approximate 30% higher risk of colon cancer than nonsmokers.

“Smoking has been linked to a modestly increased risk of colorectal cancer and use of NSAIDs has been shown to significantly decrease the risk of colorectal cancer. We wanted to see if NSAIDs could counteract the adverse effects of smoking with regard to colorectal cancer risk and whether these associations differed by tumor characteristics,” said Victoria Chia, MPH, research associate in the Hutchinson Center’s Cancer Prevention Program, in a prepared statement.

In particular, Chia and colleagues examined the impact of NSAIDs on a certain type of colorectal tumor that may be associated with smoking. Such tumors display microsatellite instability, an acquired genetic characteristic that indicates defects in DNA repair machinery. Microsatellite instability occurs in approximately 15% to 20% of colon cancers.

Study methods

The study involved 3,299 Seattle-area residents aged 20 to 74 years, 1,792 with a history of colon cancer and 1,501 without who served as controls. Cancer cases were identified through the Puget Sound Surveillance, Epidemiology and End Results (SEER) database, a population-based registry. Controls were randomly selected to match the distribution of the cases regarding age and sex.

Researchers interviewed participants by telephone about their smoking history, use of aspirin and other NSAID use and other risk factors. They assessed microsatellite instability in tumors from 1,202 cases.

Smoking was more common in cancer cases than controls and NSAID use was more common among controls than cases.

Microsatellite-unstable tumors

The researchers found a twofold increased risk of microsatellite-unstable colorectal tumors among long-term smokers who took NSAIDs, about the same risk as smokers who had not used NSAIDs.

“Given the damage that smokers receive over their lifetime, even strong antiprogression agents, like NSAIDs, may be ineffective,” the researchers wrote in Cancer Research. “NSAIDs may not be able to counteract the long-term effects of smoking, as evidenced by our observation that long-term smokers are at increased risk of colorectal cancer, despite current NSAID use.”

The link between smoking and cancer stems from the fact that cigarette smoke contains hundreds of carcinogenic metabolic products that may damage DNA. “This accumulated damage might not be reversible,” Chia said. “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.”

Researchers from the Mayo Clinic College of Medicine collaborated on the study, which was funded by the NCI and the NIH.

For more information:

Chia VM, Newcomb PA, Bigler J, et al. Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use. Cancer Res. 2006;66:6877-6883.