Cancer risk among statin users: A population‐based cohort study

Hydroxymethylglutaryl‐CoA reductase inhibitors (statins) have been linked with potential chemopreventive effects; however, the data are conflicting. We conducted a population‐based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry for the period 1989–2002. In a study population of 334,754 county residents, we compared overall and site‐specific cancer incidence among 12,251 statin users (≥2 prescriptions) with cancer incidence among nonusers and users of other lipid‐lowering drugs (n = 1,257). Statistical analyses were based on age‐standardization and Poisson regression analysis, adjusting for age, gender, calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular drugs. We identified 398 cancer cases among statin users during a mean follow‐up period of 3.3 years (range 0–14 years). The age‐ and gender‐standardized incidence rates of cancer overall were 596 per 100,000 person‐years among statin users, 645 per 100,000 person‐years among nonusers and 795 per 100,000 person‐years among users of other lipid‐lowering drugs. Adjusted rate ratios for cancer overall among statin users were 0.86 (95% CI, 0.78–0.95) compared to nonusers and 0.73 (95% CI, 0.55–0.98) compared to users of other lipid‐lowering drugs. No significantly increased or decreased rate ratios were observed for any of the studied site‐specific cancers (liver, colorectum, lung, breast, prostate, female genital organs and lymphatic and haematopoietic tissue), but most estimates tended to be less than 1.0. Stratification by duration of follow‐up or number of prescriptions revealed no clear trends. In summary, individuals prescribed statins experienced a slightly reduced cancer incidence compared to population controls of nonusers and users of other lipid‐lowering drugs. Larger and longer‐term studies are needed to determine the potentially protective effect of statin use on cancer development. © 2004 Wiley‐Liss, Inc.

[1]  Katie L Stone,et al.  Lipid-lowering drug use and breast cancer in older women: a prospective study. , 2003, Journal of women's health.

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

[3]  P. Nguyen,et al.  Comparative effects of lovastatin on mammary and prostate oncogenesis in transgenic mouse models. , 2003, Carcinogenesis.

[4]  C. Hennekens,et al.  Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. , 1997, JAMA.

[5]  J. Farmer,et al.  Comparative Tolerability of the HMG-CoA Reductase Inhibitors , 2000, Drug safety.

[6]  D. Illingworth Carcinogenicity of lipid-lowering drugs. , 1996, JAMA.

[7]  D. Wallwiener,et al.  Statins can inhibit proliferation of human breast cancer cells in vitro. , 2003, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[8]  HOMAS,et al.  The Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholesterol Levels , 2000 .

[9]  J. Avorn,et al.  HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. , 2000, JAMA.

[10]  Ann G Zauber,et al.  Statin Use and the Risk of Breast and Prostate Cancer , 2002, Epidemiology.

[11]  H. Storm,et al.  The Danish Cancer Registry--history, content, quality and use. , 1997, Danish medical bulletin.

[12]  H. Sørensen,et al.  The Danish prescription registries. , 1997, Danish medical bulletin.

[13]  H. Sørensen,et al.  Angiotensin-converting enzyme inhibitors and risk of cancer - A population-based cohort study in Denmark , 2001 .

[14]  B. Foster,et al.  Role of RhoA activation in the growth and morphology of a murine prostate tumor cell line , 1999, Oncogene.

[15]  R. Paoletti,et al.  Safety of Statins: Focus on Clinical Pharmacokinetics and Drug Interactions , 2004, Circulation.

[16]  C. Schweiger [Statins and the risk of dementia]. , 2001, Italian heart journal. Supplement : official journal of the Italian Federation of Cardiology.

[17]  J. Stein,et al.  HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2. , 2001, Carcinogenesis.

[18]  D. Capellà Descriptive tools and analysis. , 1993, WHO regional publications. European series.

[19]  S. Heckbert,et al.  The association between 3‐hydroxy‐3‐methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women , 2004, Cancer.

[20]  M. Minden,et al.  Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells , 2001, Leukemia.

[21]  H. Sørensen,et al.  Hip fracture risk in statin users—a population-based Danish case-control study , 2004, Osteoporosis International.

[22]  D. Gomez,et al.  Reduction of mouse mammary tumor formation and metastasis by lovastatin, an inhibitor of the mevalonate pathway of cholesterol synthesis , 1998, Breast Cancer Research and Treatment.

[23]  Kelvin K. W. Chan,et al.  The statins as anticancer agents. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  E. Toft,et al.  Use of lipid-lowering drugs during 1991-98 in Northern Jutland, Denmark. , 2001, British journal of clinical pharmacology.

[25]  J. Olsen,et al.  Cancer risk and mortality in users of calcium channel blockers , 2000, Cancer.

[26]  G. Celesia,et al.  Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors. , 2000, Archives of neurology.

[27]  J. Gołąb,et al.  Potential antitumor effects of statins (Review). , 2003, International journal of oncology.

[28]  Shu-mei Lai,et al.  Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, induces apoptosis and differentiation in human anaplastic thyroid carcinoma cells. , 2003, The Journal of clinical endocrinology and metabolism.

[29]  J. LeLorier,et al.  Do statins cause cancer? A meta-analysis of large randomized clinical trials. , 2001, The American journal of medicine.

[30]  Michael J. Goodman,et al.  Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women , 2000, The Lancet.

[31]  G. Thorgeirsson,et al.  Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S) , 2004, The Lancet.

[32]  M. Minden,et al.  HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis , 2002, Leukemia.

[33]  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.

[34]  M. Linton,et al.  Current perspectives on statins. , 2000, Circulation.

[35]  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.

[36]  M. Tatsuta,et al.  3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. , 2002, Gastroenterology.

[37]  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.

[38]  HMG-CoA reductase inhibitors and the risk of fractures. , 2000 .

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

[40]  G. McGwin,et al.  Association between Statin Use and Alzheimer’s Disease , 2004, Neuroepidemiology.

[41]  Y. Saito,et al.  The inhibitory effect of simvastatin on growth in malignant gliomas--with special reference to its local application with fibrin glue spray in vivo. , 2001, International journal of oncology.

[42]  J. Olsen,et al.  Lipid-lowering medication and risk of cancer. , 1999, Journal of clinical epidemiology.

[43]  A. Walker,et al.  Statin use, hyperlipidaemia, and the risk of breast cancer , 2002, British Journal of Cancer.

[44]  J. Dalen,et al.  Does lowering cholesterol cause cancer? , 1996, JAMA.