Genetic variations in the vitamin D receptor, androgen receptor and enzymes that regulate androgen metabolism.
OBJECTIVE
We review the current literature on genetic variations in the vitamin D receptor (VDR), androgen receptor (AR) and enzymes regulating androgen development.


METHODS
A MEDLINE search was conducted to identify research investigating associations between polymorphisms in important regulatory genes that may indirectly affect cancer risk, with special regard to prostate cancer.


RESULTS
Genes involved in androgen regulation, metabolism and their related pathways, and the vitamin D receptor are prime candidates for study of prostate cancer risk. Expression and nuclear activation of the VDR are necessary for the antiproliferative effects of 1alpha,25-dihydroxyvitamin D3 (calcitriol), which is involved in calcium and bone homeostasis. Several genetic variations have been identified in the VDR, and at least 1 VDR polymorphism appears to confer some predictability of prostate cancer risk in various ethnic cohorts. Interactions between the androgen receptor and circulating androgens have a major role in the development of normal and malignant prostate cells.


CONCLUSIONS
Due to the relationship between the AR and prostatic growth, it has been proposed that polymorphisms within the AR may have a role in susceptibility to prostate cancer.
Price
Douglas K
DK
Molecular Pharmacology Section, Cancer Therapeutics Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA.
Franks
Michael E
ME
Figg
William D
WD
D002117:Calcitriol / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D013254:Steroid 17-alpha-Hydroxylase; D002117:Calcitriol