High Incidence Of Prostate Cancer Research Articles

Racial disparities in prostate cancer incidence rates by census division in the United States, 1999-2008.

Black men have a higher incidence of prostate cancer than white men in the U.S., but little is known whether incidence or racial differences vary geographically. Understanding these differences may assist future studies on causes of prostate cancer. To address such, we leverage the unique resource of the National Program of Cancer Registries (NPCR) combined with Surveillance, Epidemiology and End Results (SEER). Prostate cancer counts and population denominators by race (black, white), age, calendar year, and U.S. census division, for the period 1999-2008, were extracted from NPCR and SEER. We calculated age-standardized incidence rates (ASR) and estimated annual percent changes (EAPC) by race and census division. We assessed black-to-white incidence rate ratios (BWIRR) by census division and by calendar period. This analysis included 1,713,471 prostate cancer cases and 1,217 million person-years. Black ASRs ranged from 176 per 100,000 person-years in Mountain division to 259 in Middle Atlantic. BWIRRs ranged from 1.20 in Western divisions to 1.72 in Southeastern divisions. EAPCs indicated that prostate cancer incidence is not decreasing in East South Central, unlike all other divisions. White EAPCs displayed similar variations by census division, resulting in modest temporal changes in BWIRRs. Within the U.S., there exists significant geographic variability in prostate cancer incidence rates. Although there are large geographic differences in BWIRRs, temporal trends are fairly stable. This may indicate that primary factors affecting prostate cancer incidence rates vary geographically but affect both black and white men to a similar degree.

Prevalence and clinical significance of incidental (18)F-fluoro-2-deoxyglucose uptake in prostate.

PurposeTo investigate the prevalence and clinical significance of incidental prostate fluoro-2-deoxyglucose (FDG) uptake and to evaluate its impact on patient management.Materials and MethodsOf 47,109 men who underwent FDG positron emission tomography between 2004 and 2014, 1,335 (2.83%) demonstrated incidental FDG uptake in the prostate, with 99 of the latter undergoing prostate biopsy. The primary end point was the histological presence of prostate adenocarcinoma in the biopsy specimen. Outcomes, including treatment methods, survival, and causes of death, were also assessed. Factors associated with the diagnosis of prostate cancer were evaluated by using logistic regression analysis.ResultsPatients with prostate cancer were more likely to have higher serum prostate-specific antigen (PSA) (p=0.001) and focal FDG uptake (p=0.036) than were those without. Prostate cancer occurred in 1 of 26 patients (3.8%) with serum PSA<2.5 ng/mL, compared with 40 of 67 patients (59.7%) with serum PSA≥2.5 ng/mL. Multivariable analysis showed that focal lesions (odds ratio [OR], 5.50; p=0.038), age (OR, 1.06; p=0.031), and serum PSA (OR, 1.28; p=0.001) were independent predictors of prostate cancer diagnosis. Most patients with prostate cancer had organ-confined tumors. Of these, 12 (29.3%) underwent radical prostatectomy and 25 (60.9%) received hormone therapy. Of the 11 patients who died, 9 died of primary cancer progression, with only 1 patient dying from prostate cancer.ConclusionsThe prevalence of incidental FDG uptake in the prostate was not high, although patients with elevated serum PSA had a higher incidence of prostate cancer. Patients with FDG uptake in the prostate should be secondarily evaluated by measuring serum PSA, with those having high serum PSA undergoing prostate biopsy.

Patterns of changing cancer risks with time since diagnosis of a sibling.

Family history is a well-known risk factor for many cancers. However, it is important to know if/how the familial risk of cancer changes over time. For each of four major cancers (colorectal, breast, prostate and melanoma), we identified siblings of cancer patients (case siblings) and siblings of matched cancer-free controls sampled from Swedish population-based registers. Effects of age and time since diagnosis on sibling risks were examined using Poisson regression and presented graphically as smoothed hazard ratios (HRs). Screening effects were investigated by comparing hazards before/after the introduction of mammography for breast cancer and prostate-specific antigen (PSA) testing for prostate cancer. Case siblings had higher cancer incidence than control siblings for all cancers at all ages, with overall incidence rate ratios (IRRs) of 2.41 (95% confidence interval 2.14-2.71) for colorectal cancer, 2.37 (2.24-2.52) for breast cancer, 3.69 (3.46-3.93) for prostate cancer and 3.20 (2.72-3.76) for melanoma. Risks were highest in siblings who were young when the first cancer was diagnosed in the family, with siblings aged 30-40 having IRR 9.05 (3.03-27.00) for colorectal cancer and 4.30 (2.87-6.45) for breast cancer. Smoothed HRs remained fairly constant for up to 20 years except for prostate cancer, where the HR decreased steeply during the first few years. After introduction of PSA testing, men had higher incidence of prostate cancer shortly after diagnosis in a brother, but no such screening effect was found for breast cancer. Our findings can help inform the screening and counseling of family members of cancer patients.

Association Between Penile Dynamic Contrast-Enhanced MRI-Derived Quantitative Parameters and Self-Reported Sexual Function in Patients with Newly Diagnosed Prostate Cancer

The high incidence of prostate cancer, coupled with excellent prostate cancer control rates, has resulted in growing interest in nononcological survivorship issues such as sexual function. Multiparametric magnetic resonance imaging (MRI) is increasingly being performed for local staging of prostate cancer, and due to the close anatomical relationship to the prostate, penile enhancement is often depicted in prostate MRI. To evaluate the associations between quantitative perfusion-related parameters derived from dynamic contrast-enhanced (DCE)-MRI of the penis and self-reported sexual function in patients with newly diagnosed prostate cancer. This retrospective study included 50 patients who underwent DCE-MRI for prostate cancer staging before prostatectomy. The following perfusion-related parameters were calculated: volume transfer constant (K(trans)), rate constant (k(ep)), extracellular-extravascular volume fraction (v(e)), contrast enhancement ratio (CER), area under the gadolinium curve after 180 seconds (AUC180), and slope of the time/signal intensity curve of the corpora cavernosa. Associations between perfusion-related parameters and self-reported sexual function were evaluated using the Wilcoxon Rank-Sum test. Patient responses to the sexual function domain of the Prostate Quality of Life survey. Five of the six DCE-MRI parameters (K(trans), v(e), CER, AUC180, and slope) were significantly associated with the overall score from the sexual domain of the survey (P = 0.0020-0.0252). CER, AUC180, and slope were significantly associated with the answers to all six questions (P = 0.0020-0.0483), ve was significantly associated with the answers to five of six questions (P = 0.0036-0.1029), and K(trans) was significantly associated with the answers to three of six questions (P = 0.0252-0.1023). k(ep) was not significantly associated with the overall survey score (P = 0.7665) or the answers to any individual questions (P = 0.4885-0.8073). Penile DCE-MRI parameters were significantly associated with self-reported sexual function in patients with prostate cancer. These parameters are readily available when performing prostate MRI for staging and may be relevant to the management of patients considering prostate cancer therapies.

Abstract 263: African American prostate cancer incidence rates inside and outside of zinc zones

Abstract African American males experience disproportionately higher prostate cancer incidence rates versus all other ethnic groups in the North American continent. Data indicates a decreased expression of hZIP1 zinc transporter in African American prostate tissue. Research demonstrates zinc deficiency in-vitro promotes a pro-metastatic dis-regulation of cell cycle and apoptotic processes. Research also demonstrates zinc transporter over-expression in-vitro promotes decreased pro-metastatic and anti-apoptotic activity and sensitization to ligand mediated cell death. Starting from this molecular premise, we examined the relationship between at risk populations’ proximity to zinc mines and incidence rates: hypothesizing a correlation between decreased rates within proximity to zinc mines. Data was requested from cancer registries where zinc mines were located, though only Arizona data was used. Using a combination of excel, basic image capture techniques and radius creating websites, a 100-mile radius was arbitrarily created around Ruby, Arizona where the now abandoned Montana mine is located. Counties in the state of Arizona were divided into those that fell within this radius, or outside of it. Weighted age adjusted incidence rates were then determined for each county for a given ethnic group. Averaged weighted age adjusted rates were then determined for the counties within the radius and outside. These rates were compared within each ethnic group, though one final comparison was made for all ethnicities within and outside of the radius. Maps containing additional zinc mines, locations of aquifers and main streams and the radius were super-posed to visualize the topological relationships of these elements. Our results show that every ethnic group experienced the same decrease in averaged weighted age adjusted prostate cancer incidence rates within the 100-mile radius of the zinc mine versus outside. The same result occurred when all ethnic groups were used simultaneously to compare rate differences on either side of the radius boundary. As expected, African Americans experienced the highest incidence rates within their at risk group. Asian / Pacific Islanders experienced the lowest incidence rates within their at risk group. There appears to be a correlation between the proximity of at risk populations to zinc mines and decreased prostate cancer incidence rates. The geological maps manipulated in this study provide reasonable insight into the passage of zinc from abandoned mining operations into streams and groundwater. It is from these resources that public and private wells (as well as municipal systems) draw water for human use. This basic epidemiological inquiry macroscopically mirrors the established molecular premises and leads to a holistic perspective on the subject. More rigorous statistical analyses need be performed on these data in order to properly support these conclusions. Note: This abstract was not presented at the meeting. Citation Format: Jiro D. Mckinnis, Hao Nguyen. African American prostate cancer incidence rates inside and outside of zinc zones. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 263. doi:10.1158/1538-7445.AM2014-263

Null association between vitamin D and PSA levels among black men in a vitamin D supplementation trial.

Black men exhibit a high prevalence of vitamin D deficiency as well as a higher incidence of prostate cancer and higher mortality rates from prostate cancer than Whites. There are few data about the effect of vitamin D3 (cholecalciferol) supplementation on prostate-specific antigen (PSA) in healthy Black men. During three winters from 2007 to 2010, 105 Black men (median age, 48.9 years) of Boston, MA were randomized into a four-arm, double-blind trial for 3 months of placebo, 1,000, 2,000, or 4,000 U of vitamin D3. At baseline and 3 months, free and total PSA was measured. With vitamin D supplementation, no significant differences in free and total PSA were observed; free PSA, -0.0004 ng/mL (P = 0.94) and total PSA, -0.004 ng/mL (P = 0.92) for each additional 1,000 U/d of vitamin D3. Within an unselected population of healthy Black men without a cancer diagnosis, we found no effect of vitamin D supplementation on free or total PSA. These findings support prior findings of no change in PSA with vitamin D supplementation and emphasize the need for new methods to assess the influence of vitamin D supplementation on prostate cancer prevention.

Affecting African American men's prostate cancer screening decision-making through a mobile tablet-mediated intervention.

African American men experience a 60% higher incidence of prostate cancer and are more than twice as likely to die from it than White men. Evidence is insufficient to conclude that definitively screening for prostate cancer reduces the likelihood of morbidity or death. Patients are encouraged to discuss screening alternatives with health care providers for informed decision-making (IDM). The extent of IDM in clinical or community setting is not known. This study uses data from a community-based, computer-mediated, IDM intervention that targeted 152 African American aged 40 to 70. Pretest-posttest differences in means for prostate cancer knowledge, screening decisional conflict, and screening decisional self-efficacy were examined by two-tailed t-tests. Overall, the intervention significantly improved respondents' prostate cancer knowledge (p&lt;.0001), significantly improved decisional self-efficacy (p&lt;.0001) and significantly reduced decisional conflict (p&lt;.0001). Specifically, the intervention significantly promoted IDM among men who reported more education, being married, having financial resources, and younger age.

Impact of Family History on Prostate Cancer Mortality in White Men Undergoing Prostate Specific Antigen Based Screening

We assessed whether prostate cancer screening would decrease prostate cancer mortality in white men with a family history of prostate cancer. Data from the PLCO cancer screening trial were used to compare the screening and usual care arms in the subset of men with and without a family history of prostate cancer. Univariate and multivariate Cox regression analysis, and log rank analysis of Kaplan-Meier curves were done to examine the data for differences in prostate cancer specific survival. A total of 65,179 white subjects were included in the prostate specific antigen screening trial, of whom 7,314 (11.2%) were diagnosed with prostate cancer. Only 4,833 white men (7.4%) had a family history of prostate cancer. Those with a positive family history had a significantly higher incidence of prostate cancer (16.9% vs 10.8%) and higher prostate cancer specific mortality (0.56% vs 0.37%, each p <0.01). On multivariate analysis this trended toward significance (HR 1.47, 95% CI 0.98-2.21, p = 0.06). Screening in men with a positive family history also showed a trend toward decreased prostate cancer specific mortality (HR 0.49, 95% CI 0.22-1.1, p = 0.08) and decreased time to death from prostate cancer (log rank p = 0.05). White men with a family history of prostate cancer are at increased risk for being diagnosed with and subsequently dying of prostate cancer. Yearly digital rectal examination and prostate specific antigen testing may decrease prostate cancer death in these individuals.

A single low dose of cadmium exposure induces benign prostate hyperplasia like condition in rat: A novel benign prostate hyperplasia rodent model.

Abnormal prostate growth is the most prevalent pathological sign in aged human males, as reflected by high incidence of benign prostate hyperplasia (BPH) and prostate cancer. In spite of the high prevalence, the etiology and pathophysiology of BPH is unclear due to the lack of any established rodent model for study. It has been demonstrated that the cadmium (Cd) mimics the activity of androgen or estrogen by interacting with the steroid hormone receptors in the prostate and elicits BPH, but the specific receptor which binds to Cd is still unknown. Our lab studies with BPH patients highlighted a strong co-relation between smokings with increased Cd content. Changes in the maximum urinary flow rate (Qmax) and prostatic acid phosphatase (PAP) level further supports that Cd can induce BPH like condition. Therefore, the present study was aimed to induce BPH like condition in rats by Cd administration. The dose of cadmium was standardized in an age- and time-dependent manner, which was further examined by prostate weight, histology, and PAP levels that elucidated the pathogenesis of BPH. Further to understand the molecular basis, steroid hormone receptor antagonist experiment was performed. Gene expression and immunohistochemistry data suggest that Cd induces hyperplasia like condition by activating the androgen receptor and estrogen receptor-α and suppresses the action of estrogen receptor-β. The experimental model used here is a cost effective, less time consuming and potentially valuable tool for investigating the respective functions of epithelial and stromal hormone receptors. The applicability of this model would be helpful in understanding the pathogenesis of BPH and its progression.

Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer.

The Wnt signaling pathway plays a crucial role in human cancer development, and axis inhibition protein 2 (Axin2) is a master scaffold protein involved in Wnt signaling. Axin2 negatively regulates Wnt signaling and acts as a tumor suppressor protein. The present study evaluated the association between the Axin2 single nucleotide polymorphism (SNP) rs2240308 [guanine (G)/adenine (A)] and the incidence of prostate cancer. In total, 103 patients with prostate cancer and 100 cancer-free control males were included in this case-control study, and were genotyped using the genomic DNA extracted from peripheral blood samples. The results revealed a higher incidence of prostate cancer in the subjects with the homozygous GG genotype and a reduced cancer incidence in the patients with the GA genotype of the rs2240308 SNP (G/A) in the Axin2 gene. The adjusted odds ratio for carriers with the GA genotype was 0.377 (95% CI, 0.206–0.688; P=0.001) and that for the AA genotype was 0.830 (95% CI, 0.309–2.232; P=0.712) compared with the GG genotype. Therefore, the GA genotype was found to exhibit a protective effect that decreased the risk of prostate cancer. To the best of our knowledge, this is the first study to demonstrate the significant association between this SNP (rs2240308, G/A) and the risk of prostate cancer. This association indicates the possibility that the variations in the Axin2 gene in this position may play a significant role in promoting the development of cancer in the prostate. We believe that the Axin2 SNP (rs2240308) could be a useful biomarker for the predisposition and early diagnosis of the disease.

Effects of eicosapentaenoic acid and the GPR120 agonist TUG‐891 on lysophosphatidic acid signaling in human prostate cancer cells (1066.10)

There is a high incidence of prostate cancer in the Western world, which may be partially attributed to Western diets that are generally deficient in omega‐3 fatty acids (n‐3 FAs). Dietary n‐3 FAs have been shown to inhibit proliferation of prostate cancer cells in culture. The G protein‐coupled receptor GPR120, which is expressed in normal prostate and prostate tumors, serves as a receptor for the n‐3 FA eicosapentaenoic acid (EPA). We therefore hypothesized that the inhibitory effects of n‐3 FAs on prostate cancer cell proliferation are mediated by GPR120. To test this hypothesis, we performed proliferation and signal transduction studies, comparing the effects of lysophosphatidic acid (LPA), EPA, the GPR120 agonist TUG‐891, and the GPR40 agonist GW9508 in DU145 and PC‐3 cells. We found that EPA and TUG‐891 inhibit proliferation of human prostate cancer cells in response to LPA. In addition, brief (15 minute) pre‐incubation of serum‐starved cells with EPA or TUG‐891 suppresses subsequent activation of ERK, p70S6K, and FAK in response to LPA. This rapid effect of EPA is consistent with mediation by a GPCR. Our data suggest that GPR120 shows promise as a therapeutic target in prostate cancer.Grant Funding Source: Washington State University College of Pharmacy

CBP Loss Cooperates with PTEN Haploinsufficiency to Drive Prostate Cancer: Implications for Epigenetic Therapy

Despite the high incidence and mortality of prostate cancer, the etiology of this disease is not fully understood. In this study, we develop functional evidence for CBP and PTEN interaction in prostate cancer based on findings of their correlate expression in the human disease. Cbp(pc-/-);Pten(pc+/-) mice exhibited higher cell proliferation in the prostate and an early onset of high-grade prostatic intraepithelial neoplasia. Levels of EZH2 methyltransferase were increased along with its Thr350 phosphorylation in both mouse Cbp(-/-); Pten(+/-) and human prostate cancer cells. CBP loss and PTEN deficiency cooperated to trigger a switch from K27-acetylated histone H3 to K27-trimethylated bulk histones in a manner associated with decreased expression of the growth inhibitory EZH2 target genes DAB2IP, p27(KIP1), and p21(CIP1). Conversely, treatment with the histone deacetylase inhibitor panobinostat reversed this switch, in a manner associated with tumor suppression in Cbp(pc-/-);Pten(pc+/-) mice. Our findings show how CBP and PTEN interact to mediate tumor suppression in the prostate, establishing a central role for histone modification in the etiology of prostate cancer and providing a rationale for clinical evaluation of epigenetic-targeted therapy in patients with prostate cancer.

OP1-02 THE ASSOCIATION BETWEEN MIF-173 G>C POLYMORPHISM AND PROSTATE CANCER IN SOUTHERN CHINESE.

You have accessJournal of UrologyOutstanding Posters: Research1 Apr 2014OP1-02 THE ASSOCIATION BETWEEN MIF-173 G>C POLYMORPHISM AND PROSTATE CANCER IN SOUTHERN CHINESE. Ninghong Song and Huang Su Ninghong SongNinghong Song More articles by this author and Huang SuHuang Su More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.610AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Accumulating epidemiological and molecular evidence suggests that inflammation is an important component in the etiology of PCa. Macrophage migration inhibitory factor (MIF) plays an important role in the pro- and anti-inflammatory response to infection. This study is aimed at investigating the potential association between MIF-173 G>C polymorphism, Gleason score, clinical stage, and prostate-specific antigen (PSA) value with respect to PCa incidence among the Han nationality in Southern China. METHODS Genotyping was performed by using tetraprimer polymerase chain reaction (PCR) on 259 PCa patients and 301 cancer-free controls. RESULTS We found that the MIF-173*C variant allele was significantly associated with an increased risk of PCa [adjusted odd ratio (OR) = 2.99, 95% confident interval (CI): 1.94-4.60] and higher Gleason scores from the PCa subjects (adjusted OR = 10.72, 95% CI: 5.35-21.49). In addition, we noted that the MIF -173*C variant allele was related to higher clinical stages and PSA values in PCa patients (adjusted OR = 15.68, 95% CI: 7.40-33.23; adjusted OR = 4.37, 95% CI: 2.41-7.92, respectively). CONCLUSIONS Our data suggest that MIF-173 polymorphisms may be associated with a higher incidence of prostate cancer compared to controls, and appears to be associated with higher Gleason scores, higher clinical stages, and PSA values in those with prostate cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e162 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Ninghong Song More articles by this author Huang Su More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prostate Cancer Mortality in Areas With High and Low Prostate Cancer Incidence

BackgroundThe effect of prostate-specific antigen (PSA) screening on prostate cancer mortality remains debated, despite evidence from randomized trials. We investigated the association between prostate cancer incidence, reflecting uptake of PSA testing, and prostate cancer mortality.MethodsThe study population consisted of all men aged 50 to 74 years residing in eight counties in Sweden with an early increase in prostate cancer incidence and six counties with a late increase during two time periods. Incidence of metastatic prostate cancer was investigated in the period from 2000 to 2009, and prostate cancer–specific mortality and excess mortality were investigated in the period from 1990 to 1999 and the period from 2000 to 2009 by calculating rate ratios for high- vs low-incidence counties and rate ratios for the period from 2000 to 2009 vs the period from 1990 to 1999 within these two groups. All statistical tests were two-sided.ResultsThere were 4528134 person-years at risk, 1577 deaths from prostate cancer, and 1210 excess deaths in men with prostate cancer in high-incidence counties and 2471373 person-years at risk, 985 prostate cancer deaths, and 878 excess deaths in low-incidence counties in the period from 2000 to 2009. Rate ratios in counties with high vs low incidence adjusted for time period were 0.81 (95% confidence interval [CI] = 0.73 to 0.90) for prostate cancer– specific mortality and 0.74 (95% CI = 0.64 to 0.86) for excess mortality, and the rate ratio of metastatic prostate cancer was 0.85 (95% CI = 0.79 to 0.92).ConclusionsThe lower prostate cancer mortality in high-incidence counties reflecting a high PSA uptake suggests that more-intense as compared with less-intense opportunistic PSA screening reduces prostate cancer mortality.

Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy. Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases. Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020). Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc.

Isoflavones in Japanese and Caucasian men with prostate cancer in Hawaii.

241 Background: Recently, several studies have reported that soy isoflavones and the ability to produce Equol, an active derivative of soy isoflavone, may play a role in the suppression of prostate cancer. An Equol-producing bacterium, Slackia sp. strain NATTS has been identified in stool cultures. To further investigate this relationship, we evaluated Japanese-Americans (JA) and whites (W) in Hawaii, with and without prostate cancer, with regards to dietary soy intake, serum isoflavone levels, and the presence of stool NATTS. Methods: The serum levels of Daidzein, Genistein, Glysitein, Dihydrodaidzein (DHD), Equol, o-desmethylangolensin (o-DMA) and total isoflavone was determined in 65 JA (34 patients with prostate cancer , 31 controls) and 68 W (34 patients with prostate cancer , 34 controls) subjects. The control group consisted of age matched cancer-free male subjects. To evaluate Equol producing ability, we assessed the presence of NATTS in stool samples. All subjects completed a lifetime dietary soy consumption survey. Results: The serum level of Genistein and o-DMA were significantly higher in JA (Genistein: W 21.5±54.0, JA 61.8±150.9, p=0.04; o-DMA: W 0, JA 2.0±7.9, p=0.04). Daizein level trended higher in JA (W 13.9±34.7, JA 33.3±84.0, p=0.09). Glysitein level was significantly higher in W (W 35.7±10.4, JA 30.7±15.5, p=0.03). No differences were noted in DHD and Equol levels between W and JA. Total isoflavone level trended higher in JA (W 76.3±104.9, JA 135.1±245.6, p=0.07). There were no differences in serum isoflavone level between prostate cancer patients and controls for both JA and W. Only 10 of 120 stool samples were positive for NATTS (8.6%), a rate much lower than seen in Japan. JA showed higher intake of soy than W. Conclusions: The high soy consumption and isoflavone levels in JA may be related to the observed lower incidence of prostate cancer relative to W in Hawaii. The near absence of equal producers in Hawaii JA may contribute to their higher incidence of prostate cancer compared to Japan based Japanese. These results suggest that both soy isoflavone levels and Equol production may be inversely associated with prostate cancer incidence.

Pluripotent Stem Cell within the Prostate could be Responsible for Benign Prostate Hyperplasia in Human

Aim: Abnormal prostate growth is the most prevalent pathological sign in aged human males, reflected by high incidence of Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PCa). The successful isolation and cultivation of prostate cells, is a prerequisite need for establishing model cell line for understanding the pathogenesis, unique biological properties and also various evidences suggest role of stem cells in pathogenesis of these conditions for therapeutic point of view. Methods and results: Here we isolate a candidate pluripotent stem cell population from BPH patients underwent TURP which include the isolation of an enriched population of prostate stem cells through cell culture techniques and the cultivation of prostate stem cells in vitro and characterization of these cells and their stem potential, including in-vivo teratoma generation. Cytogenetic analysis by G-banding assay demonstrated an aneuploid karyotype with a model chromosome number of 60 and normal Y chromosome. Characterization of isolated cells showed the presence of ONS pluripotency stem cell markers. Beside this these cells were also found positive for stem cell surface markers such as CD49b, CD44, CD117, CD34 and prostatic tissue specific markers like p63 and Androgen Receptor. In-vitro differentiation of the cells demonstrated formation of a tri-germinal layer into ectodermal, endodermal and mesodermal cell lineages with defined medium conditions and In-vivo teratoma formation in excised tumor in Balb/c mouse. Conclusion: we report here isolation, establishment and characterization of human prostate-derived pluripotent stem cell line. The cell line eventually serves as a potential tool for studies in prostate adult stem cell research, understanding etiopathophysiology and the regulation of BPH and PCa.

The Dark Side of 5α-Reductase Inhibitors' Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression

With aging, abnormal benign growth of the prostate results in benign prostate hyperplasia (BPH) with concomitant lower urinary tract symptoms (LUTS). Because the prostate is an androgen target tissue, and transforms testosterone into 5α-dihydrotestosterone (5α-DHT), a potent androgen, via 5α-reductase (5α-R) activity, inhibiting this key metabolic reaction was identified as a target for drug development to treat symptoms of BPH. Two drugs, namely finasteride and dutasteride were developed as specific 5α-reductase inhibitors (5α-RIs) and were approved by the U.S. Food and Drug Administration for the treatment of BPH symptoms. These agents have proven useful in the reducing urinary retention and minimizing surgical intervention in patients with BPH symptoms and considerable literature exists describing the benefits of these agents. In this review we highlight the adverse side effects of 5α-RIs on sexual function, high grade prostate cancer incidence, central nervous system function and on depression. 5α-Rs isoforms (types 1-3) are widely distributed in many tissues including the central nervous system and inhibition of these enzymes results in blockade of synthesis of several key hormones and neuro-active steroids leading to a host of adverse effects, including loss of or reduced libido, erectile dysfunction, orgasmic dysfunction, increased high Gleason grade prostate cancer, observed heart failure and cardiovascular events in clinical trials, and depression. Considerable evidence exists from preclinical and clinical studies, which point to significant and serious adverse effects of 5α-RIs, finasteride and dutasteride, on sexual health, vascular health, psychological health and the overall quality of life. Physicians need to be aware of such potential adverse effects and communicate such information to their patients prior to commencing 5α-RIs therapy.

Future directions in the prevention of prostate cancer.

The high global incidence of prostate cancer has led to a focus on chemoprevention strategies to reduce the public health impact of the disease. Early studies indicating that selenium and vitamin E might protect against prostate cancer encouraged large-scale studies that produced mixed clinical results. Next-generation prostate cancer prevention trials validated the impact of 5α-reductase inhibitors in hormone-responsive prostate cancer, and these results were confirmed in follow-up studies. Other interventions on the horizon, involving both dietary and pharmacological agents, hold some promise but require further investigation to validate their efficacy. In this Review, we discuss the clinical and preclinical evidence for dietary and pharmacological prevention of prostate cancer and give an overview of future opportunities for chemoprevention.

To Adjust or Not in Studies on Racial Differences in Hormone Concentrations? Depends on the Question!

To Adjust or Not in Studies on Racial Differences in Hormone Concentrations? Depends on the Question!