Polymorphisms in Genes Involved in Androgen Pathways as Risk Factors for Prostate Cancer

Purpose

Prostate cancer is epidemic in Western society and androgens are known to mediate key physiological processes in prostate tissue. Therefore, endogenous androgens have long been considered risk factors for prostate cancer. We reviewed the association of androgen pathway genes and their polymorphic sites, and the risk of prostate cancer in individuals of different ethnic backgrounds.

Materials and Methods

A PubMed^® search was performed using the key words, prostate cancer, and 20 select gene names combined with variant and polymorphism. Relevant articles and references during 1998 to 2008 were reviewed for data on the association between polymorphisms and prostate cancer risk.

Results

Recent data suggested that androgen pathway genes have a role in prostate cancer susceptibility. However, the effects of polymorphisms seem to vary in different patients, populations and ethnic backgrounds. The most studied genetic variants are those of AR, SRD5A2, CYP17A1 and CYP3A loci, and the most recent intriguing data come from SHBG and SULT2A genes, of which relatively few studies have been performed.

Conclusions

The association between androgen pathway gene polymorphisms and prostate cancer risk is complex and characterized by contradictory results. The cause of this conflict in any particular association of genotype and phenotype is difficult to identify and it can be attributable to biological, statistical and technical causes. However, recent developments that reach beyond single gene studies, such as genome scale single nucleotide polymorphism studies and multinational collaborations, are a great prospect for future study and understanding more complex interactions.

Key Words: prostate, prostatic neoplasms, androgens, gene polymorphisms, continental population groups

Abbreviations and Acronyms: 17βHSD, 17β-hydroxysteroid dehydrogenase, AKR1C3, 3α-hydroxysteroid dehydrogenase, AR, androgen receptor, BPH, benign prostatic hyperplasia, CYP, cytochrome P450, DHEA, dehydroepiandrosterone, DHT, dihydrotestosterone, HSD17B, 17β-hydroxysteroid dehydrogenase, HSD3B, hydroxy-δ-5-steroid dehydrogenase type 3, LH, luteinizing hormone, PCa, prostate cancer, PSA, prostate specific antigen, SHBG, sex hormone binding globulin, SNP, single nucleotide polymorphism, SRD5A2, steroid 5α-reductase type II, SULT, sulfotransferase, UGT, uridine diphosphate-glucuronosyl transferase enzyme, UTR, untranslated region