Page 235 - Vitamin D and Cancer

222 C.M. Barnett and T.M. Beer

Keywords Skin cancer • Solar UV radiation • Vitamin D • Epidemiology • Prevention
• Vitamin D receptor • 1,25-dihydroxyvitamin D • Keratinocytes • Differentiation
• Photoprotection • Vitamin D analogs • Prostate cancer

Disclosure OHSU and Dr. Beer have a significant financial interest in Novacea a
company that may have a commercial interest in the results of this research and
technology. This potential conflict of interest has been reviewed and managed by
OHSU and the Integrity Program Oversight Council.

Abbreviations

AIPC Androgen independent prostate cancer
ASCENT AIPC Study of Calcitriol Enhancing Taxotere
AUC Area under the concentration curve
C max Peak blood calcitriol concentrations
EGFR Epidermal growth factor receptors
NMU N-nitroso-N-methylurea
NSAIDS Non-steroidal anti-inflammatory agents
RXR Retinoid-X receptor
VDR Vitamin D receptors
VDRE Vitamin D response element

10.1 Introduction

Stimulated by epidemiological observations that suggest links between low vitamin
D exposure and increased risk of prostate cancer [1, 2], a number of investigators
have sought to examine the hypothesis that vitamin D receptor (VDR) signaling
may impact prostate cancer risk, progression, outcomes, and treatment. This work
continues to this day and has yielded encouraging but also conflicting results.

10.2 Vitamin D Physiology

Vitamin D is an important regulatory hormone in the human body that belongs to
the steroid receptor superfamily. Its calcium regulatory activity is well known, but
additional roles for vitamin D are being increasingly recognized. The principal
hormonally active form of vitamin D, 1,25-OH vitamin D, is synthesized through
2
a number of steps starting with conversion of 7-deoxycholesterol to pre-vitamin D
catalyzed by UV-B sunlight. Pre-vitamin D is then converted to 25-OH vitamin D in
the liver by the enzyme 25-hydroxylase. The enzyme 1-alpha-hydroxylase is
needed for the final conversion of 25-OH vitamin D to 1,25-OH vitamin D.
2