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

SEATTLE -- It is widely known that the use of aspirin and other nonsteroidal anti-inflammatory drugs, or NSAIDS, may reduce the risk of colorectal cancer by up to 40 percent, but this protective effect may not extend to long-term smokers, who already face an increased risk of the disease, according to a study led by researchers at Fred Hutchinson Cancer Research Center.

In a large, population-based study comparing risk factors in people with and without colorectal cancer, the researchers found the highest risk of colon cancer to be among long-term smokers of 20 or more years who had never used NSAIDs. The researchers also found that smokers who used NSAIDs were still at an approximate 30 percent higher risk of colon cancer than nonsmokers.

The findings, which appear in the July 1 issue of Cancer Research, arise from the first study of its kind to examine the effects of NSAID use on colorectal-cancer risk among smokers, said first author Victoria Chia, a research associate in the Hutchinson Center's Cancer Prevention Program.

"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," she said.

In particular, Chia and colleagues were interested in examining 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, or MSI, occurs in approximately 15 percent to 20 percent of colon cancers.

The researchers found a two-fold 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 anti-progression agents, like NSAIDs, may be ineffective," the authors wrote. "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."

Funded by the National Cancer Institute and the National Institutes of Health, the study involved 3,299 Seattle-area residents between the ages of 20 and 74 (mean age 60), approximately half with a history of colon cancer and approximately half without, who served as a control, or comparison group. Cancer cases were identified through the Puget Sound Surveillance, Epidemiology and End Results Program, a population-based registry. Controls were randomly selected to match the distribution of the cases regarding age and sex. Participants were interviewed by telephone about their smoking history and use of aspirin and other NSAID use, among other risk factors. Microsatellite instability was assessed 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.

Researchers from the Mayo Clinic College of Medicine collaborated on the study.

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