Statin use and its effect on all-cause mortality of melanoma patients: a population-based Dutch cohort study.

Elisabeth Livingstone,Dirk Schadendorf,Arjen Joosse,Esther De Vries,Bastian Schilling,Lonneke Van De Poll‐Franse,Loes M Hollestein,Tamar Nijsten,Myrthe P P Van Herk‐Sukel

doi:10.1002/cam4.285

Elisabeth Livingstone, Dirk Schadendorf + Show 7 more

Open Access

https://doi.org/10.1002/cam4.285

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Abstract

Preclinical data showed anticancer effects of statins in melanoma, but meta-analyses could not demonstrate a reduced melanoma incidence in statin users. Rather than preventing occurrence, statins might reduce growth and metastatic spread of melanomas and ultimately improve survival. In this population-based study, we investigated the relationship between statin use and survival of melanoma patients. Patients ≥18 years who were diagnosed with cutaneous melanoma (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in PHARMO Database Network between 1 January 1998 and 31 December 2010 were eligible. The hazard ratio (HR) of all-cause mortality was calculated by employing adjusted time-dependent and time-fixed Cox proportional hazard models. Disease-specific survival was estimated by means of 3-year relative survival rates (RSR). A control cohort of randomly selected patients using statins from PHARMO Database Network matched on age and gender was used to compare RSR of statin users to the general population. After melanoma diagnosis, 171 of 709 patients used statins. Use of statins showed a nonsignificantly decreased hazard of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50–1.61). After stratification for gender, male but not female statin users showed a favorable outcome compared to nonusers (HR 0.57, 95% CI 0.32–0.99; HR 1.22, 95% CI 0.62–2.38, respectively). Three-year RSR for male statin users tended to be higher than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved survival of melanoma patients. The trend for better survival of male in contrast to female statin users warrants further research.

Highlights

Melanoma is the deadliest form of skin cancer and responsible for 80% of skin cancer deaths [1]
In our cohort of 709 melanoma patients with a Breslow thickness >1 mm, statin use did not significantly impact overall survival, but our results indicate that statin use might lead to differential survival of melanoma patients depending on gender
Stratification on gender, demonstrated possible superior survival of statin users compared to nonusers in males only

Summary

Introduction

Melanoma is the deadliest form of skin cancer and responsible for 80% of skin cancer deaths [1]. Statins are frequently used to prevent cardiovascular diseases and block the enzyme 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, the rate-limiting step in de novo cholesterol synthesis [5]. They may have anticancer properties—either as a direct effect of the lowered cholesterol levels leading to decreased proliferation and migration of cancer cells [6, 7], a reduction in the downstream products of the mevalonate pathway [8, 9], or through other pleiotropic effects on the cellular level. In melanoma, antiproliferative, proapoptotic, and immunomodulatory effects of statins have been shown in cell lines [10,11,12,13,14] and mouse models [14,15,16,17]

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