HNF1b is involved in prostate cancer risk via modulating androgenic hormone effects and coordination with other genes.

Prostate cancer is one of the most commonly diagnosed male malignancies. Genome wide association studies have revealed HNF1b to be a major risk gene for prostate cancer susceptibility. We examined the mechanisms of involvement of HNF1b in prostate cancer development. We integrated data from Gene Expression Omnibus prostate cancer genes from the Dragon Database of Genes Implicated in Prostate Cancer, and used meta-analysis data to generate a panel of HNF1b-associated prostate cancer risk genes. An RT-PCR was used to assess expression levels in DU145, PC3, LNCaP, and RWEP-1 cells. Twelve genes (BAG1, DDR1, ERBB4, ESR1, HSPD1, IGFBP2, IGFBP5, NR4A1, PAWR, PIK3CG, RAP2A, and TPD52) were found to be associated with both HNF1b and prostate cancer risk. Six of them (BAG1, ERBB4, ESR1, HSPD1, NR4A1, and PIK3CG) were mapped to the KEGG pathway, and submitted to further gene expression assessment. HNF1b, NR4A1, and HSPD1 were found to be highly expressed in the LNCaP androgenic hormone-dependent cell line. Compared to expression levels in wild-type prostate cancer cells, NR4A1, HSPD1, ERBB4, and ESR1 expression levels were also found to be significantly increased in the HNF1b-transfected cells. We conclude that the mechanism of action of HNF1b in prostate cancer involves modulation of the association between androgenic hormone and prostate cancer cells. Gene-gene interaction and coordination should be taken into account to determine relationships between specific loci and diseases.

Oestradiol is a protective factor for non-alcoholic fatty liver disease in healthy men.

Visceral fat is a risk factor for non-alcoholic fatty liver disease (NAFLD). A reduction in sex hormones is associated with increased abdominal fat. Thus, we investigated whether reduced testosterone (T) or oestradiol (E2) levels in men are associated with NAFLD and central obesity. The study involved a survey of 1,882 men between 20 and 60 years of age. We detected hepatic fat infiltration by ultrasound. Early morning serum was analyzed for total testosterone (TT), E2, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Free testosterone (FT) was calculated using the Vermeulen method. In the studied population, the prevalence of NAFLD, FSH, LH and SHBG increased with age, TT and FT declined with age, and E2 remained stable. However, in the NAFLD group, TT remained stable, FT and E2 declined, and hepatic fat infiltration increased (P < 0.001 for both). Using multivariate analysis, a correlation was found between E2 and NAFLD, with an odds ratio of 0.954 (95% confidence interval: 0.946-0.967). E2 is one of the protective factors against NAFLD in healthy men. T has no significant correlation with NAFLD. Further investigation would be required to assess the clinical consequences of reduced E2 in men with NAFLD, particularly for men whose TT remained stable.

Key pathways involved in prostate cancer based on gene set enrichment analysis and meta analysis.

Prostate cancer is one of the most common male malignant neoplasms; however, its causes are not completely understood. A few recent studies have used gene expression profiling of prostate cancer to identify differentially expressed genes and possible relevant pathways. However, few studies have examined the genetic mechanics of prostate cancer at the pathway level to search for such pathways. We used gene set enrichment analysis and a meta-analysis of six independent studies after standardized microarray preprocessing, which increased concordance between these gene datasets. Based on gene set enrichment analysis, there were 12 down- and 25 up-regulated mixing pathways in more than two tissue datasets, while there were two down- and two up-regulated mixing pathways in three cell datasets. Based on the meta-analysis, there were 46 and nine common pathways in the tissue and cell datasets, respectively. Three up- and 10 down-regulated crossing pathways were detected with combined gene set enrichment analysis and meta-analysis. We found that genes with small changes are difficult to detect by classic univariate statistics; they can more easily be identified by pathway analysis. After standardized microarray preprocessing, we applied gene set enrichment analysis and a meta-analysis to increase the concordance in identifying biological mechanisms involved in prostate cancer. The gene pathways that we identified could provide insight concerning the development of prostate cancer.

Early and late long-term effects of vasectomy on Zn, Cd, and Cu levels in prostatic fluid and serum.

AIM: To evaluate the early and late long-term effects of vasectomy on the serum and prostatic fluid trace elements. METHODS: In 37 vasectomized and 25 non-vasectomized (control) men, the Zn, Cd and Cu levels in the serum and prostatic fluid were measured by means of inductively coupled plasma-atomic emission spectroscopy (ICP-AES). RESULTS: No significant difference was found in the prostatic Zn, Cd and Cu levels between the vasectomized and control group. The Zn level in the serum were significantly lower in the vasectomized men than in the controls (11.04 and 13.54 umol/L, respectively; P < 0.05), while the serum Cd and Cu levels were not significantly different between the two groups. CONCLUSION: Vasectomy may decrease the serum, but not the prostatic Zn levels. Its pathophysiological significance is worthy of further investigation.

Early and late long-term effects of vasectomy on serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels.

PURPOSE: We investigated whether the association between vasectomy and prostate cancer has a hormonal basis. MATERIALS AND METHODS: We examined serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels by radioimmunoassay on 91 pairs of men who did and did not undergo vasectomy. RESULTS: Men who underwent vasectomy 10 to 19 years previously had higher dihydrotestosterone levels than age matched controls. In men who underwent vasectomy 20 years or more ago testosterone was higher than in corresponding controls. No statistically significant difference in luteinizing hormone and follicle-stimulating hormone levels was noted between the men who had had vasectomy and controls. CONCLUSIONS: Our results indirectly support the hypothesis that there is an elevated risk of prostate cancer among men who underwent vasectomy 20 or more years previously.

PIP: Researchers compared data on 91 men who had undergone vasectomy at least 10 years earlier with data on 91 healthy men matched for age, weight, height, and neighborhood who had not undergone vasectomy to examine whether the link between vasectomy and prostate cancer is based on changes in serum hormone levels. All the men lived in suburban Xiangtan in Hunan Province, China. Cases had a higher mean serum dihydrotestosterone level than controls (1.18 vs. 1.05 nmol/l; p 0.05). Yet men who had undergone vasectomy less than 20 years earlier not only had a higher dihydrotestosterone level than age-matched controls (1.46 vs. 1.22 nmol/l; p 0.01) but had a lower testosterone/dihydrotestosterone ratio (14.5 vs. 20.1; p 0.005). On the other hand, men who had undergone vasectomy more than 20 years earlier had a higher testosterone level than age-matched controls (27.2 vs. 23.9 nmol/l; p 0.05). Men who had undergone vasectomy when they were less than 35 years old had a higher FSH level and those who were 35-39 years old at vasectomy had a higher dihydrotestosterone level than age-matched controls (19.5 vs. 14.8 mIU/ml and 1.31 vs. 1.09 nmol/l) (p 0.05). Even though men who were at least 40 years old at vasectomy had a higher dihydrotestosterone level than matching controls (1.24 vs. 1.09 nmol/l), the difference was not statistically significant. These findings suggest that vasectomy may cause a reduction in testosterone levels by minimizing the conversion from testosterone to dihydrotestosterone in the long term. Thus, they support the hypothesis that a long-term effect of vasectomy may be an elevated risk of prostate cancer. More research is needed to confirm or refute this hypothesis.