Genetic Variations in the Vitamin D Receptor, Androgen Receptor and Enzymes that Regulate Androgen Metabolism

ABSTRACT 

Purpose

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

Materials and 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 1α,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.

Key Words:  vitamin D, prostatic neoplasms , receptors, androgen