Molecular epidemiology of prostate cancer: androgens and polymorphisms in androgen-related genes

Abstract

In most western countries prostate cancer is the most commonly diagnosed non-skin cancer in men. Despite its high morbidity and mortality the etiology of prostate cancer remains obscure. The involvement of androgens has been examined extensively in prostate carcinogenesis but the results of most epidemiological studies remain inconclusive. This review focuses on current perspectives of androgen levels and polymorphisms in androgen-related genes. Racial differences in genetic polymorphisms that have a role in the biosynthesis and metabolism of androgens may partly account for racial differences in prostate cancer risk. Reasons are also given for inconsistent results in molecular epidemiological studies and insights and directions for future research are discussed. The development of a polygenic model for prostate cancer, incorporating multiple loci from the individual genes, may maximize the chance of identifying individuals with high-risk genotypes, resulting in better preventive, diagnostic, and therapeutic strategies.

Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients

“…Androgen binding induces dissociation from heat shock proteins, hyperphosphorylation, conformational changes, and dimerization of the receptor. The binding affinity of DHT to the prostatic AR is 5 times higher than that of testosterone (29).…”

“…Lack of normal function could affect testosterone concentrations, in turn influencing the risk of PC (9). Aromatase mRNA and protein have both been detected in BPH and PC tissue (29). In light of these data, normal and benign prostates clearly have the capacity to locally metabolize androgens to estrogens via aromatase.…”

The androgen receptor and prostate cancer: A role for sexual selection and sexual conflict?

“…Because the AR mediates the effects of testosterone, it is intimately involved in the development of secondary sexual characteristics [22]. Hence, this receptor is an important locus for the action of sexual selection, and it influences many aspects of male display and male competitive ability in species subject to strong sexual selection on males.…”

A novel polymorphism in the 17β-hydroxysteroid dehydrogenase type 5 (aldo-keto reductase 1C3) gene is associated with lower serum testosterone levels in caucasian men

“…Although testosterone is one of the major androgens in the circulation, DHT is a key androgen in peripheral tissues, particularly in the prostate. 1 The action of these androgens is mediated via the androgen receptor (AR) and is crucial for men's health. 2 Testosterone and DHT are strongly associated with the development and progress of prostate cancer.…”