Purpose Evidence suggests statins may influence pathways of RCC proliferation though no study has examined the influence of statin medications on progression of RCC in humans. at surgery. Statin users experienced similar pathological characteristics compared to nonusers. With a median follow-up of 36 months there were 247 progression events. Statin use was associated with a 33% reduction in the risk of progression after surgery Rabbit polyclonal to IQCC. (HR 0.67 95 CI 0.47-0.96 p=0.028) and an 11% reduction in overall mortality that was not significant (HR 0.89 95 CI 0.71-1.13 p=0.3). Modeling statin use as time-dependent covariate attenuated the risk reduction in progression to 23% (HR 0.77 p=0.12) and augmented the risk reduction in overall survival (HR 0.71; LY2886721 p=0.002). Conclusions In our cohort statin use was associated with a reduced risk of progression and overall mortality though this effect was sensitive to method of analysis. If validated in LY2886721 other cohorts this obtaining warrants concern of prospective research on statins in the adjuvant setting. with varied results.14-17 However these studies lack power with limited long-term follow-up and numbers of incident RCCs. To date no scholarly study has explored the association between statin use and LY2886721 progression after primary treatment for RCC. There is certainly rationale suggesting statins may reduce progression nevertheless. A small amount of animal and laboratory studies recommend statins may inhibit RCC progression. Woodard et al. implemented fluvastatin to two RCC cell lines 786 and CaKi-2.8 Fluvastatin inhibited growth and induced apoptosis within a dose-dependent way. Moreover fluvastatin seemed to straight focus on the Akt/mTOR pathway suppressing phosphorylation and therefore activation of AkT reducing downstream mTOR activation. As the mTOR pathway continues to be implicated in the pathogenesis of RCC as LY2886721 well as the mTOR inhibitors everolimus and temsirolimus possess established benefits in metastatic LY2886721 RCC the discovering that statins inhibit RCC through an identical pathway is pertinent. Bil et al. examined lovastatin with sorafenib or sunitinib in the Renca RCC cell line.18 They observed lovastatin potentiated the cytotoxic ramifications of sorafenib however not sunitinib and induced cell routine arrest in the G1 stage. Horiguchi et al finally. noticed that fluvastatin furthermore to inhibiting proliferation of Renca cell lines also inhibited angiogenesis and invasion two essential mechanisms necessary for development and metastasis.9 They validated these findings LY2886721 by xenografting Renca cells into mice and observed fluvastatin inhibited pulmonary metastases. Statins have already been been shown to be connected with a lower threat of prostate cancers development after radiotherapy 19 and after medical procedures;20 plus they have been connected with reduced risk of breast malignancy recurrence after main therapy.21 22 Recently a large population-based study of 300 0 Danish malignancy patients observed statin users were 15% less likely to die from all cancers (HR 0.85 95 CI 0.82-0.87). In a supplementary table they reported statin use was associated with a similar 15% reduction in risk of dying from RCC (2 717 of 124 0 malignancy deaths) but this findings did not reach statistical significance (HR 0.85 95 CI 0.72-1.01). While strengthened by figures and integrity of exposure and malignancy data this study is limited by lack of information on comorbidities. We found a statistically significant 33% reduction in progression for statin users at surgery. Considering our sensitivity analysis accounted for the 204 (8%) patients who subsequently started statin use on average nearly 4 years after surgery it is not surprising the hazard ratio for progression was attenuated. Statin use remained associated with a reduction in progression (23%) but this was no longer statistically significant. These patients may not have had sufficient exposure to statins prior to progression. In our main analysis statin use was associated with an overall survival benefit of 11% though not statistically significant. This is nearly identical to the overall survival benefit seen in studies of non-cancer patients on statins 23 and similar to the overall survival benefit seen in the latest Danish study of most cancer sufferers.24 Our finding of too little dosage- and duration- dependent statin impact will not lend support to a causal association. Nevertheless.