Association Between Serum Sex Hormone Levels and Prostate Cancer: Effect of Prostate Cancer on Serum Testosterone Levels

Igarashi, Takashi; Suzuki, Hiroyoshi; Utsumi, Takanobu; Endo, Takumi; Takano, Makoto; Yano, Masashi; Kawamura, Koji; Nihei, Naoki; Naya, Yukio; Ichikawa, Tomohiko

doi:10.2217/fon.09.82

Cited by 13 publications

(14 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The final elongation step was performed at 72˚C for 10 min. Each PCR product (261 bp) was digested at 37˚C for 16 h by the restriction enzyme RsaI (5 units, Fermentas, Denmark) in order to determine the presence of the V89L variant (9), separated by the Microchip Electrophoresis system for DNA/RNA Fragment Analysis MCE ® -202 MultiNA (Shimadzu, Japan). The common SRD5A2-89V allele retained the RsaI restriction site at the polymorphic region and generated 21-, 62-and 169-bp frag-ments.…”

Section: Methodsmentioning

confidence: 99%

“…Androgens, testosterone and dihydrotestosterone (DHT) are actively involved in the growth and development of the prostate, and appear to be essential for carcinogenesis in the prostate gland (9). In total, 80-90% of prostate cancers are dependent on androgens at initial diagnosis, and endocrine therapy of prostate cancer is directed towards the reduction of serum androgens and inhibition of the androgen receptor (10,11).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphism of the SRD5A2 gene and the risk of prostate cancer

Dusenka

Tomaskin

Kliment

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Androgens are actively involved in the development of the prostate gland and appear to be essential for prostate carcinogenesis. The product of the SRD5A2 gene, membrane-bound steroid 5-α-reductase, type II enzyme, is key in testosterone metabolism. The present study explored the association between the SRD5A2 V89L gene polymorphism and the risk of developing prostate cancer. The study cohort consisted of 456 male Slovak patients, including 260 cases with histologically confirmed prostate cancer and 196 age-matched controls without any clinically suspected infections of the prostate. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the SRD5A2 polymorphism on codon 89. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) for different allele variants were calculated in order to determine the association between the SRD5A2 V89L gene polymorphism and prostate cancer. The distribution of V89L variants in the control group was consistent with the Hardy-Weinberg equilibrium (χ 2 test, P=0.266) with a significant deviation in the case group (χ 2 test, P=0.04). However, no association between the SRD5A2 polymorphism and an increased risk of developing prostate cancer was identified. When the wild type VV variant was used as a reference, the ORs for different allele variants ranged from 1.11 (95% CI 0.66-1.87, P=0.70) for the LL genotype to 0.99 (95% CI 0.68-1.46, P=0.99) for the LL + VL genotypes. No particular allele variant was identified to exhibit an increased capacity to promote the development of highly aggressive prostate cancer (Gleason ≥7) or induce carcinogenesis at an earlier onset (<65 years of age). It was confirmed that in the population studied, the SRD5A2 V89L polymorphism was not associated with the risk of prostate cancer and SRD5A2 was not shown to be a key gene involved in prostate cancer development. Published data indicate that a combination of multiple genetic changes are required for prostate cancer development, rather than a single gene change. Therefore, it was hypothesized that high-throughput genotyping may be more effective than single nucleotide polymorphism detection.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphism of the SRD5A2 gene and the risk of prostate cancer

Dusenka

Tomaskin

Kliment

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Some early studies demonstrated that plasma T levels might be correlated with Gleason grade or time to progression after orchiectomy of CaP (3,4). However, other studies indicated no evidence of any association between plasma T, estradiol (E2), SHBG with Gleason score at the time of diagnosis (5, 6). Thus, there is insufficient evidence to support the hypothesis that higher blood levels of steroid hormones are associated with CaP development or progression.…”

Section: Introductionmentioning

confidence: 97%

The Impact of Common Genetic Variations in Genes of the Sex Hormone Metabolic Pathways on Steroid Hormone Levels and Prostate Cancer Aggressiveness

Oh¹,

Jacobus²,

Regan³

et al. 2011

Cancer Prevention Research

View full text Add to dashboard Cite

Background Our previous work suggested that there was no significant association between plasma steroid hormone levels and prostate cancer (CaP) tumor grade at diagnosis. In this study, we systematically tested the hypothesis that inherited variations in the androgen and estrogen metabolic pathways may be associated with plasma levels of steroid hormones, or CaP aggressiveness at diagnosis. Methods Plasma hormone levels including total testosterone, total estradiol and sex hormone-binding globulin were measured in a cohort of 508 patients identified with localized CaP. D’Amico risk classification at diagnosis was also determined. 143 single nucleotide polymorphisms (SNPs) from 30 genes that are involved in androgen and estrogen metabolism were selected for analysis. The global association of genotypes with plasma hormone levels and CaP aggressiveness (D’Amico risk classification) was statistically analyzed. Q-values were estimated to account for multiple testing. Results We observed significant associations between plasma testosterone level and SNPs in HSD17B2 (rs1424151), HSD17B3 (rs9409407) and HSD17B1 (rs12602084), with P values of 0.002, 0.006 and 0.006, respectively. We also observed borderline significant associations between prostate aggressiveness at diagnosis and SNPs in AKR1C1 (rs11252845; P = 0.005), UGT2B15 (rs2045100; P = 0.007) and HSD17B12 (rs7932905; P = 0.008). No individual SNP was associated with both clinical variables. Conclusions Genetic variants of genes in hormone metabolic pathways may influence plasma androgen levels or CaP aggressiveness. However, it appears that the inherited variations affecting plasma hormone levels differ from those affecting disease aggressiveness.

show abstract

“…There is conflicting evidence for the role of androgens in the development of prostate cancer (PC) [1]. In a previous study, it was reported that PC patients with a low dihydrotestosterone (DHT) level at diagnosis had a higher risk of dying from PC than those with a high level [2].…”

Section: Introductionmentioning

confidence: 99%