Statins and Cancer Development

Abstract

There is epidemiologic evidence that the hydrophilic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitor pravastatin increases the incidence of some extrahepatic cancers, although this finding has been attributed to chance. We hypothesize that pravastatin is able to promote the development of cancer by causing an induction of HMG-CoA reductase and, hence, mevalonate synthesis in extrahepatic tissues. We have shown that mevalonate, the product of HMG-CoA reductase, promotes the growth of breast cancer cells. Because there is no uptake of pravastatin by most extrahepatic cells, this statin will be unable to mitigate the increase in mevalonate synthesis in extrahepatic tissues that accompanies the decrease in circulating cholesterol caused by its inhibition of hepatic HMG-CoA reductase. (Cancer Epidemiol Biomarkers Prev 2005;14(8):1897 -8)

Statin use and prostate cancer risk in a large population-based setting

“…Our results on type of statin also support evolving evidence that hydrophobic statins have antiproliferative effects on certain cancer cells [39][40][41]. It has been suggested that hydrophilic statins promote cancer [39], but our results suggest an inverse association between hydrophilic statin use and prostate cancer risk.…”

“…To make conclusions about the effect of statins on prostate cancer prevention, mechanistic data suggests that the type, dose, and potency of statin used and the serum concentrations achieved need to be considered in observational studies [39,43]. We agree with Platz that the promising and consistent findings from the most recently published studies are remarkable [44], but many of the specifics on statin use (e.g., individual statins, potency) have not been adequately addressed, and the influence of detection bias [44] as well as other confounders such as socioeconomic status need further study.…”

Statin Use and Breast Cancer Risk in a Large Population-Based Setting

“…Researchers have hypothesized hydrophobic statins to have antiproliferative effects on breast cancer cells (31,32) and hydrophilic statins to promote cancer (33). We were unable to evaluate hydrophilic statin use due to the small number of hydrophilic only statin users in our cohort.…”

Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells

“…On the other hand, hydrophilic statins have no inhibitory effect on HMG-CoA reductase activity in cells with an extrahepatic origin, while statins are involved in mevalonic acid synthesis and could potentially increase carcinogenic risk (32)(33)(34).…”