Statin Use After Colorectal Cancer Diagnosis and Survival A Population-Based Cohort Study

SUMMARY: Approximately 32 million Americans take a statin in the United States. Statins (3-Hydroxy-3-MethylGlutaryl coenzyme A reductase inhibitors) are usually prescribed to lower LDL cholesterol. Cholesterol is a structural component of cell membranes and a reduction in the availability of cholesterol can result in decreased proliferation and migration of cancer cells. The six statin drugs available in the United States include LIPITOR® (Atorvastatin), ZOCOR® (Simvastatin), CRESTOR® (Rosuvastatin), MEVACOR® (Lovastatin), PRAVACHOL® (Pravastatin) and LESCOL® (Fluvastatin). Statin use in cancer patients has been associated with a reduction in cancer related mortality in several clinical studies. This benefit has been attributed to the inhibition of HMG-CoA reductase, which is a rate limiting enzyme in the mevalonate and cholesterol synthesis pathway. The mevalonate pathway is upregulated by mutated p53 (tumor suppressor gene) which is often expressed in cancer cells. By inhibiting the mevalonate pathway, statins can reduce isoprenoid levels such as farnesylpyrophosphate (F-PP) and geranylgeranylpyrophosphate (GG-PP). These isoprenoids are essential for the posttranslational modification of several proteins involved in important intracellular signaling pathways and therefore play a crucial role in cell growth, proliferation, survival and migration. Statins also inhibit angiogenic pathways and proteasomes, thereby negatively impacting cell proliferation and survival. Survival benefit with statin use after colorectal cancer diagnosis has been unclear. To answer this question, the authors identified a cohort of patients (N=7657) diagnosed with stage I to III colorectal cancer from 1998 to 2009, in the National Cancer Data Repository (English Cancer Registry). Information on statin use was obtained from medical records of patients and in this cohort of patients 35% were identified to have used statin drugs following diagnosis of colorectal cancer. Twenty percent of these patients had stage I disease, 43% had stage II disease and 37% had stage III disease. Patients were followed up for 14 years following their diagnosis of colorectal cancer. Statin use after a diagnosis of colorectal cancer was associated with a 29% reduction in colorectal cancer-specific mortality (HR= 0.71). There was a dose-response association with a 36% reduction in colorectal cancer-specific mortality with statin use for more than 1 year (HR=0.64). Statin users after colorectal cancer diagnosis also had a 25% reduction in all-cause mortality (HR=0.75). The authors concluded that based on this large population based colorectal cancer cohort, statin use following diagnosis of colorectal cancer was associated with longer rates of survival. Cardwell CR, Hicks BM, Hughes C, et al. J Clin Oncol 2014;32:3177-3183