Douglas K Price1, Michael E Franks, William D Figg. 1. Molecular Pharmacology Section, Cancer Therapeutics Branch, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA.
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 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.
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 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.
Authors: Yong Xu; Fang Fang; Daret K St Clair; Sajni Josson; Pradoldej Sompol; Ivan Spasojevic; William H St Clair Journal: Mol Cancer Ther Date: 2007-06-29 Impact factor: 6.261