Cancer Prevention Research 14-0280 Published OnlineFirst April 2, 2015; doi: 10.1158/1940-6207.
Clara Curiel-Lewandrowski1,*, Jean Y. Tang2, Janine G. Einspahr3, Yira Bermudez4, Chiu-Hsieh Hsu5, Melika Rezaee6, Alex Hao Lee6, Joseph Tangrea7, Howard L. Parnes8, David S. Alberts9, and H-H S Chow4
1Dermatology, The University of Arizona Cancer Center
2Dermatology, Stanford School of Medicine, Stanford University
3Medicine, The University of Arizona Cancer Center
4Medicine, University of Arizona
5The University of Arizona Cancer Center
6Dermatology, Stanford University
7Cancer Prevention, National Institute of Health
9University of Arizona
↵* Corresponding Author:
Clara Curiel-Lewandrowski, Dermatology, The University of Arizona Cancer Center, 1515 N. Campbell Avenue, Tucson, AZ, 85724, United States ccuriel at email.arizona.edu
Laboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral VD supplementation would exert direct bioactivity in human skin through modulation of the VD-receptor. We enrolled 25 individuals with serum 25-hydroxyvitamin-D levels <30 ng/mL and with skin photodamage to take 50,000 IU of VD3 biweekly for 8-9 weeks. Then, we obtained baseline and end-of-study skin biopsies from photodamaged (PD) and photoprotected (PP) skin, and from benign nevi (BN) and tested for mRNA expression of VD-receptor (VDR) and cytochrome P450-24 (CYP24), and markers of keratinocytic differentiation. High dose VD supplementation significantly elevated circulating levels of 25-hydroxyvitamin-D (p<0.0001) and 1,25-dihydroxyvitamin-D (p<0.0001). VDR expression in PD- and PP-skin showed minimum changes after supplementation. CYP24 expression in PD- and PP-skin was increased after supplementation by 186%, p=0.08, and 134%, p=0.07, respectively.
In BNs from 11 participants, a trend for higher VDR and CYP24 expression was observed (average of 20%, p=0.08, and 544%, p=0.09, respectively).
Caspase-14 expression at the basal layer in PD skin samples was the only epidermal differentiation marker that was significantly increased (49%, p<0.0001).
High-dose vitamin D supplementation raised serum VD levels concurrently with CYP24 mRNA and Caspase-14 levels in the skin. Our findings of significant variability in the range of VDR and CYP24 expression across study samples represent an important consideration in studies evaluating the role of VD as a skin cancer chemopreventive agent.
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