Statins and the risk of colorectal cancer.

BACKGROUND Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and effective lipid-lowering agents. Statins inhibit the growth of colon-cancer cell lines, and secondary analyses of some, but not all, clinical trials suggest that they reduce the risk of colorectal cancer. METHODS The Molecular Epidemiology of Colorectal Cancer study is a population-based case-control study of patients who received a diagnosis of colorectal cancer in northern Israel between 1998 and 2004 and controls matched according to age, sex, clinic, and ethnic group. We used a structured interview to determine the use of statins in the two groups and verified self-reported statin use by examining prescription records in a subgroup of patients for whom prescription records were available. RESULTS In analyses including 1953 patients with colorectal cancer and 2015 controls, the use of statins for at least five years (vs. the nonuse of statins) was associated with a significantly reduced relative risk of colorectal cancer (odds ratio, 0.50; 95 percent confidence interval, 0.40 to 0.63). This association remained significant after adjustment for the use or nonuse of aspirin or other nonsteroidal antiinflammatory drugs; the presence or absence of physical activity, hypercholesterolemia, and a family history of colorectal cancer; ethnic group; and level of vegetable consumption (odds ratio, 0.53; 95 percent confidence interval, 0.38 to 0.74). The use of fibric-acid derivatives was not associated with a significantly reduced risk of colorectal cancer (odds ratio, 1.08; 95 percent confidence interval, 0.59 to 2.01). Self-reported statin use was confirmed for 276 of the 286 participants (96.5 percent) who reported using statins and whose records were available. CONCLUSIONS The use of statins was associated with a 47 percent relative reduction in the risk of colorectal cancer after adjustment for other known risk factors. Because the absolute risk reduction is likely low, further investigation of the overall benefits of statins in preventing colorectal cancer is warranted.

[1]  M. Minden,et al.  Increased sensitivity of acute myeloid leukemias to lovastatin-induced apoptosis: A potential therapeutic approach. , 1999, Blood.

[2]  B. Davis,et al.  The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. , 1996, The New England journal of medicine.

[3]  A. Gotto,et al.  Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin. , 2001, The American journal of cardiology.

[4]  G. Beck,et al.  A randomized trial of aspirin to prevent colorectal adenomas. , 2003, The New England journal of medicine.

[5]  R. Collins,et al.  Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. , 1998, The New England journal of medicine.

[6]  P. Macfarlane,et al.  Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia , 1995 .

[7]  J. Long,et al.  Genetic anthropology of the colorectal cancer-susceptibility allele APC I1307K: evidence of genetic drift within the Ashkenazim. , 2003, American journal of human genetics.

[8]  C. Rao,et al.  Lamin B, caspase-3 activity, and apoptosis induction by a combination of HMG-CoA reductase inhibitor and COX-2 inhibitors: a novel approach in developing effective chemopreventive regimens. , 2002, International journal of oncology.

[9]  C. Rao,et al.  Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. , 1999, Gastroenterology.

[10]  Barry R. Davis,et al.  Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). , 2002, JAMA.

[11]  H. Buchwald Cholesterol inhibition, cancer, and chemotherapy , 1992, The Lancet.

[12]  F. Bernini,et al.  Safety of HMG-CoA Reductase Inhibitors: Focus on Atorvastatin , 2004, Cardiovascular Drugs and Therapy.

[13]  M. Sinensky,et al.  Recent advances in the study of prenylated proteins. , 2000, Biochimica et biophysica acta.

[14]  A. Jemal,et al.  Cancer Statistics, 2005 , 2005, CA: a cancer journal for clinicians.

[15]  L. G. García Rodríguez,et al.  Reduced Risk of Colorectal Cancer among Long-Term Users of Aspirin and Nonaspirin Nonsteroidal Antiinflammatory Drugs , 2001, Epidemiology.

[16]  Susan Halabi,et al.  A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. , 2003, The New England journal of medicine.

[17]  C. Elson,et al.  Sterol‐independent regulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase in tumor cells , 2001, Molecular carcinogenesis.

[18]  AndrewJ. S. Coats MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial , 2002, The Lancet.

[19]  H Jick,et al.  Statin use and cancer risk in the General Practice Research Database , 2004, British Journal of Cancer.

[20]  C. Rao,et al.  Chemopreventive effect of farnesol and lanosterol on colon carcinogenesis. , 2002, Cancer detection and prevention.

[21]  L. Blais,et al.  3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of cancer: a nested case-control study. , 2000, Archives of internal medicine.

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

[23]  J. Willerson Effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. , 1996, Circulation.

[24]  J. Goldstein,et al.  Regulation of the mevalonate pathway , 1990, Nature.

[25]  B. Davis,et al.  Safety and Tolerability of Pravastatin in Long-Term Clinical Trials: Prospective Pravastatin Pooling (PPP) Project , 2002, Circulation.

[26]  P. Serruys,et al.  Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. , 2002, JAMA.

[27]  M. Clearfield Mortality and incidence of cancer during 10-year follow-up of the Scandinavian simvastatin survival study. , 2005, Current atherosclerosis reports.

[28]  P. Macfarlane,et al.  Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial , 2002, The Lancet.

[29]  Jennifer L. Kelsey,et al.  Methods in Observational Epidemiology , 1986 .

[30]  Henk-Jan Guchelaar,et al.  The risk of cancer in users of statins. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

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

[32]  J E Frijters,et al.  A short questionnaire for the measurement of habitual physical activity in epidemiological studies. , 1982, The American journal of clinical nutrition.

[33]  E. Shemesh,et al.  Colorectal adenomatous polyps and carcinoma in ashkenazi and non‐ashkenazi jews in israel , 1986, Cancer.