title: Genetic polymorphisms in the androgen metabolism pathway and risk of prostate cancer in low incidence Malaysian ethnic groups.
abstract: Androgens are involved in prostate cancer (PCa) cell growth. Genes involved in androgen metabolism mediate key steps in sex steroid metabolism. This study attempted to investigate whether single nucleotide polymorphisms (SNPs) in the androgen metabolism pathway are associated with PCa risk in low incidence Asian ethnic groups. We genotyped 172 Malaysian subjects for cytochrome P450 family 17 (CYP17A1), steroid-5-alpha-reductase, polypeptide 1 and 2 (SRD5A1 and SRD5A2), and insulin-like growth factor 1 (IGF-1) genes of the androgen metabolism pathway and assessed the testosterone, dihydrotestosterone and IGF-1 levels. SNPs in the CYP17A1, SRD5A1, SRD5A2, and IGF-1 genes were genotyped using real-time polymerase chain reaction. Although we did not find significant association between SNPs analysed in this study with PCa risk, we observed however, significant association between androgen levels and the IGF-1 and several SNPs. Men carrying the GG genotype for SNP rs1004467 (CYP17A1) had significantly elevated testosterone (P = 0.012) and dihydrotestosterone (DHT) levels (P = 0.024) as compared to carriers of the A allele. The rs518673 of the SRD5A1 was associated with prostate specific antigen (PSA) levels. Our findings suggest CYP17A1 rs1004467 SNP is associated with testosterone and DHT levels indicating the importance of this gene in influencing androgen levels in the circulatory system of PCa patients, hence could be used as a potential marker in PCa assessment.
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia.
authors.forename: Prevathe
authors.initials: P
authors.lastname: Poniah
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia.
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia.
authors.forename: Yamunah Devi
authors.initials: YD
authors.lastname: Apalasamy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia.
authors.forename: Shamsul
authors.initials: S
authors.lastname: Mohd Zain
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia.
authors.forename: Shanggar
authors.initials: S
authors.lastname: Kuppusamy
authors.affiliation: Department of Surgery, Faculty of Medicine, University of Malaya Kuala Lumpur 50603, Malaysia.
authors.forename: Azad Ha
authors.initials: AH
authors.lastname: Razack
keywords: Prostate cancer; androgen; dihydrotestosterone; insulin-like growth factor 1; single nucleotide polymorphism; testosterone