Editors' ChoiceCancer

Statins are skin safe, now go innovate!

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Science Translational Medicine  20 Dec 2017:
Vol. 9, Issue 421, eaar4438
DOI: 10.1126/scitranslmed.aar4438


Epidemiological data demonstrate no overall increased risk of skin cancer with statin use.

Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA), are effective cholesterol-lowering drugs and are among the most prescribed medications in the United States. Overall, statins are considered safe, but a few recent studies raised concern about the potential for statins to increase the risk of skin cancers: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) [collectively known as keratinocyte carcinomas (KC)], as well as malignant melanoma (MM). Therefore, Lin et al. analyzed two large data sets to explore the relationship between use of oral statins and the risk of developing skin cancer.

They studied over 57,000 females and over 21,000 males from the Nurses’ Health Study and the Health Professionals Follow-up Study, respectively. Using Cox proportional hazards regression models, the authors did not find any overall association between hypercholesterolemia or statin use and increased risk of BCC, SCC, or MM. Unlike in previous studies, the investigators adjusted for multiple covariates associated with skin cancer development, increasing the expected validity of the results. A separate statistical model accounting for duration of statin use demonstrated a dose-dependent increase in risk of BCC, but only in men. Compared with other statins, pravastatin lowered risk of BCC (in a separate analysis for men or men and women combined, but not for women alone), whereas lovastatin increased risk of SCC (in women or men and women combined, but not in men alone).

These data are encouraging given the large population currently using oral statins. The finding that these drugs do not increase risk of cutaneous neoplasms is especially relevant considering that the safety profile of statins and their anti-inflammatory properties have made these molecules an attractive target for topical drug discovery, and multiple patents have been registered for topical statin use. Additionally, this analysis suggests that statin selection does matter. Previous data suggested increased risk of KC with the naturally occurring, lipophilic simvastatin and lovastatin, and the latter was partially confirmed in the study by Lin et al. Conversely, the new study showed that pravastatin, the naturally occurring lipophobic statin, was protective against KC, suggesting that the difference in risk may relate to degree of fat solubility in addition to cumulative dose, although all of this will need to be confirmed with mechanistic studies.

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