Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA
Clara Curiel-Lewandrowski1, Jean Tang2, Janine Einspahr1, Yira Bermudez1, Chiu-Hsieh Hsu3, Melika Rezaee2, Alex Lee2, Joe Tangrea4, Howard Parnes4, David Alberts1, and H-H. Sherry Chow1
1University of Arizona Cancer Center, Tucson, AZ;
2Stanford University, Stanford, CA;
3University of Arizona, Tucson, AZ;
4National Cancer Institute, Bethesda, MD.
Experimental studies suggest that vitamin D (VD) plays an important role in skin carcinogenesis. In humans, epidemiologic studies have reported mixed findings in the association between circulating vitamin D levels and skin cancer risk. We conducted a pilot clinical study to determine whether oral VD supplementation would exert any bioactivity in human skin.
Methods: The study accrued twenty-five healthy individuals with serum 25-hydroxyvitamin D levels <30 ng/mL and with moderate to severe photodamage on the forearms.
Participants took 50,000 IU of VD3 capsules twice a week for 8-9 weeks. Baseline and end-of study skin biopsies were obtained from photodamaged (PD) and photoprotected (PP) skin, and benign nevi (BN), when available, for assessment of changes in putative biomarkers of VD activity. Biomarkers evaluated include the mRNA expression of vitamin D receptor (VDR) and cytochrome P450 24 (CYP24) in keratinocytes and available BN. In addition, molecular markers of keratinocytic differentiation (caspase 14 and loricrin protein expression), epidermal thickness, serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were assessed.
Results: High dose VD supplementation significantly elevated the circulating levels of 25-hydroxyvitamin D from 21.6 ± 5.2 to 70.5 ± 18.2 ng/mL (p < 0.0001) and 1,25-dihydroxyvitamin D from 31.1 ± 12.4 to 51.4 ± 13.5 pg/mL (p < 0.0001).
VDR expression in PD- and PP-skin showed minimum changes after VD supplementation.
CYP24 expression in PD- and PP-skin showed a non-statistically significant increase after VD supplementation (average of 186% increase, p = 0.08, and 134% increase, p=0.07, respectively). Higher VDR and CYP24 expression was observed in BNs collected at post-intervention than that at baseline from eleven participants, but the difference did not reach statistical significance (average of 20% higher, p = 0.08, and 544% higher, p= 0.09, respectively).
The large inter-subject variation in VDR and CYP24 expression may have limited the statistical evaluation. The epidermal differentiation markers did not change significantly after VD supplementation with the exception of a 49% increase (p< 0.0001) in caspase 14 expression at the basal layer in PD skin samples.
When epidermal thickness was analyzed, the only significant change was identified when the analysis was stratified by the baseline median thickness. Samples with baseline thickness below or equal to the median exhibited a significant increase in thickness at the end of the intervention.
Conclusion: The study showed that following effective oral supplementation based on VD serum levels, subtle indicators of increased keratinocytic differentiation and CYP24 activation can be observed. Future studies evaluating the role of VD as a skin cancer chemopreventive agent with biomarker modulation as an endpoint should be considered before larger intervention studies are implemented in at risk populations.
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