Oncology Statins Might Reduce Risk of Renal Cell Carcinoma in Humans: Case-Control Study of 500,000 Veterans Vikas Khurana, Gloria Caldito, and Murali Ankem OBJECTIVES Statins are commonly used cholesterol-lowering agents noted to suppress tumor cell growth in several in vitro and animal models. METHODS We studied the association between renal cell carcinoma and statins in veterans. A retrospective nested case-control study was conducted using prospectively collected data from the Veterans Integrated Service Networks 16 Veteran Affairs database from 1998 to 2004. We analyzed the data from 483,733 patients from eight states located in the south-central United States. The primary variables of interest were renal cell carcinoma and the use of statins before the diagnosis of renal cell carcinoma. Multiple logistic regression analysis was done to adjust for covariates, including age, sex, body mass index, and smoking. Statistical Analysis Systems software was used for statistical computing. RESULTS Of the 483,733 patients in the study, 164,441 (34%) were taking statins before the diagnosis of renal cell carcinoma and 1446 (0.3%) had a primary diagnosis of renal cell carcinoma. Statin use was significantly associated with a risk reduction of renal cell carcinoma of 48% (adjusted odds ratio 0.52, 95% confidence interval 0.45 to 0.60). Furthermore, the protective effect of statins was seen across different age and sex groups and was irrespective of the presence of obesity and smoking. CONCLUSIONS Statins appear to be protective against the development of renal cell carcinoma, after controlling for age, sex, smoking, and obesity. UROLOGY 71: 118 –122, 2008. © 2008 Elsevier Inc. R enal cell carcinoma accounts for approximately 2% of all new primary cancer cases diagnosed in United States, with an estimated 30,000 new cases every year and an associated 11,000 deaths annu- ally. 1 Renal cell carcinoma is diagnosed incidentally by abdominal imaging done for unrelated reasons. Radical surgical extirpation is the standard of care for locore- gional disease. The estimated cancer-specific 5-year sur- vival rate is about 81.3% after curative resection. 2 The major cause of death is metastatic disease. Radiotherapy, chemotherapy, and immunotherapy have a limited role in the treatment of advanced renal cell carcinoma. Renal cell carcinoma is rare before the age of 30 years. How- ever, the incidence increases exponentially thereafter and peaks in the fourth and sixth decades. Men have a greater incidence (2:1) and mortality rate than women worldwide. Tobacco smoking, obesity, and a family his- tory 1 are the three known probable risk factors of renal cell carcinoma. Statins are widely used drugs for the treatment of lipid disorders, especially hypercholesterolemia. Their role in the reduction of mortality and morbidity in both pri- mary 3 and secondary prevention of coronary artery dis- ease is well proven. They also reduce long-term cerebro- vascular events, particularly after an initial coronary event. 4 In addition, they have pleiotropic cardiovascular and antiatherosclerotic effects, including improving en- dothelial function, reduction of free radical formation, stabilization of plaques, and inhibition of endothelial inflammatory reactions, which contribute to other poten- tial benefits for patients at risk of cardiovascular disease, regardless of cholesterol levels. 5 Because of these effects, statins are currently one of the most widely prescribed drugs in the United States. Statins are generally well tolerated and have a safe side-effect profile, with most concerning adverse effects hepatotoxicity and myotoxic- ity. Recently, statins have also been recognized for their activity against various types of cancers. The use of statins as anticancer agents is based on preclinical evi- dence of their antiproliferative, proapoptotic, anti-inva- sive, and radiosensitizing properties. Initially, concern From the Gastroenterology Service and Urology Service, Overton Brooks Veterans Affairs Medical Center; and Departments of Gastroenterology, Bioinformatics and Computational Biology, and Urology, Louisiana State University Health Sciences Center, Shreveport, Louisiana Reprint requests: Murali Ankem, M.D., Urology Service, Overton Brooks Veterans Affairs Medical Center, 510 East Stoner Avenue, Shreveport, LA 71101. E-mail: murali.ankem2@va.gov Submitted: December 13, 2006; accepted (with revisions): August 16, 2007 118 © 2008 Elsevier Inc. 0090-4295/08/$34.00 All Rights Reserved doi:10.1016/j.urology.2007.08.039