Reduced Risk of Colorectal Cancer among Long-Term Users of Aspirin and Nonaspirin Nonsteroidal Antiinflammatory Drugs

Use of nonsteroidal antiinflammatory drugs (NSAIDs) has been associated with a reduced risk of colorectal cancer, but limited information is available on the effect of individual nonaspirin NSAIDs. In addition, the dose-response relation of aspirin in reducing the risk of colorectal cancer has not been described. We carried out a population-based cohort study with secondary case-control analysis to determine the association between the risk of colorectal cancer and use of aspirin and individual NSAIDs, including the role of dose and duration. The General Practice Research Database in the U.K. was the source population. We traced 943,903 persons 40–79 years of age and free of cancer and colorectal adenoma between January 1994 and September 1997. A total of 2,002 incident cases of colorectal cancer were ascertained. The incidence rate of colorectal cancer per 10,000 person-years was 7.3. The risk of colorectal cancer was reduced in users of nonaspirin NSAIDs and became evident after 6 months of continuous treatment. The adjusted relative risk was 0.5 (95% confidence interval = 0.4–0.7). The reduction in risk disappeared completely 1 year after stopping NSAID treatment. The risk of developing colorectal cancer was reduced in long-term users of aspirin at doses of 300 mg daily (relative risk = 0.6; 95% confidence interval = 0.4–0.9). Daily doses of 75 and 150 mg aspirin were not associated with a reduced risk of colorectal cancer. Our data support the existence of an important protective effect of nonaspirin NSAID continuous intake against colorectal cancer and point to a similar reduction in risk for aspirin at doses of at least 300 mg daily. One-year treatment with NSAIDs would prevent one case of colorectal cancer in a population of 1,000 persons 70–79 years of age.

[1]  L. G. García Rodríguez,et al.  Use of the UK General Practice Research Database for pharmacoepidemiology. , 1998, British journal of clinical pharmacology.

[2]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[3]  J. F. Fraumeni,et al.  Incidence of cancer among patients with rheumatoid arthritis. , 1993, Journal of the National Cancer Institute.

[4]  H Jick,et al.  Validation of information recorded on general practitioner based computerised data resource in the United Kingdom. , 1991, BMJ.

[5]  L. G. García Rodríguez,et al.  Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. , 1998, Archives of internal medicine.

[6]  R. Coffey,et al.  Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. , 1994, Gastroenterology.

[7]  S. Shapiro,et al.  A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large-bowel cancer. , 1991, Journal of the National Cancer Institute.

[8]  R. Everson,et al.  Aspirin Use and Lung, Colon, and Breast Cancer Incidence in a Prospective Study , 1994, Epidemiology.

[9]  M. Rawlins,et al.  Prophylactic aspirin and risk of peptic ulcer bleeding , 1995, BMJ.

[10]  N. Petrelli,et al.  Aspirin use, cancer, and polyps of the large bowel , 1993, Cancer.

[11]  W. Ray,et al.  Use of nonsteroidal anti-inflammatory drugs and incidence of colorectal cancer: a population-based study. , 1999, Archives of internal medicine.

[12]  G. Cooper,et al.  A national population‐based study of incidence of colorectal cancer and age. Implications for screening in older Americans , 1995, Cancer.

[13]  S. H. Brown,et al.  Aspirin and nonsteroidal anti-inflammatory drug use and the risk of subsequent colorectal cancer. , 1994, Archives of internal medicine.

[14]  J. Hanley,et al.  Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing , 1999, British Journal of Cancer.

[15]  M. Thun,et al.  Aspirin use and risk of fatal cancer. , 1993, Cancer research.

[16]  S. Shapiro,et al.  Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma , 1998, Cancer.

[17]  G. Morgan.  Nonsteroidal antiinflammatory drugs and colorectal cancer , 1995, Cancer.

[18]  P. Remington,et al.  Nonsteroidal anti-inflammatory drug use and protection against colorectal cancer in women. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[19]  L F Watson,et al.  Colorectal cancer risk, chronic illnesses, operations and medications: case control results from the Melbourne Colorectal Cancer Study. 1988. , 2007, International journal of epidemiology.

[20]  J. Potter,et al.  Drugs and colon cancer , 1998, Pharmacoepidemiology and drug safety.

[21]  J. Manson,et al.  Aspirin Use and Colorectal Cancer: Post-Trial Follow-up Data from the Physicians' Health Study , 1998, Annals of Internal Medicine.

[22]  B. Henderson,et al.  Aspirin use and chronic diseases: a cohort study of the elderly. , 1989, BMJ.

[23]  M. Schuler.  Aspirin and the risk of colorectal cancer in women. , 1996, The New England journal of medicine.

[24]  E. Rimm,et al.  Aspirin Use and the Risk for Colorectal Cancer and Adenoma in Male Health Professionals , 1994, Annals of Internal Medicine.

[25]  P. Kleihues,et al.  An international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.