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A Population-Based Study

Walter Smalley, MD, MPH; Wayne A. Ray, PhD; James Daugherty, MS; Marie R. Griffin, MD, MPH

Arch Intern Med. 1999;159:161-166.

Background  Previous observational studies have provided limited information on the effect of specific nonsteroidal anti-inflammatory drugs (NSAIDs) and different patterns of use (duration and dose) on the incidence of colorectal cancer.

Objective  To determine how patterns of use (duration, dose, and specific drug) of NSAIDs affect incidence of colorectal cancer.

Design  Population-based retrospective cohort study.

Setting  Tennessee Medicaid Program, 1985-1992.

Subjects  Enrollees (n = 104,217) aged 65 years or older with at least 5 years of enrollment.

Main Outcome Measures  Incident histologically confirmed colorectal cancer.

Results  Users of nonaspirin NSAIDs for at least 48 months of the previous 5 years had a relative risk (RR) of 0.49 (95% confidence interval [CI], 0.24-1.00) for colon cancer when compared with those with no use of NSAIDs. Among those with more than 12 months of cumulative use, those using NSAIDs in the past year (recent users) had an RR of 0.61 (95% CI, 0.48-0.77), whereas those with no recent use had an RR of 0.76 (95% CI, 0.50-1.15). No specific NSAID offered a unique protective effect and low doses of NSAIDs appeared to be at least as effective as higher doses. Protection was most pronounced for right-sided lesions. The RR among recent users with more than 12 months of cumulative use was 0.81 (95% CI, 0.49-1.32) for rectal cancer, 0.77 (95% CI, 0.55-1.08) for left-sided colon cancer, and 0.48 (95% CI, 0.34-0.68) for right-sided colon cancer.

Conclusions  In this elderly population, long-term use of nonaspirin NSAIDs nearly halved the risk of colon cancer. This study was consistent with previous studies that suggest that duration of use but not daily dose of NSAIDs is an important factor for chemoprevention. Our data also suggest that the protective effect is shared by most NSAIDs, and not confined to a small number of these drugs.

From the Department of Medicine, Veterans Affairs Medical Center, and the Division of Gastroenterology (Dr Smalley), the Department of Preventive Medicine (Drs Smalley, Ray, and Griffin and Mr Daugherty), and the Division of General Internal Medicine (Dr Griffin), Vanderbilt University, Nashville, Tenn.

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