Quality of life for androgen receptor targeted agents in patients with metastatic castration resistant prostate cancer.

BACKGROUND: Few studies have evaluated health-related quality of life (HRQoL) with abiraterone acetate plus prednisone (abiraterone) compared to enzalutamide in metastatic castration resistant prostate cancer (mCRPC). So, this study aimed to assess impact of abiraterone and enzalutamide on patients´ functioning in mCRPC real-world setting. METHODS: In this 12-month, prospective, observational study, 36 mCRPC patients from Slovakia were included. Patients were treated with abiraterone or enzalutamide according to routine practice. HRQoL was assessed at baseline and 3-/6-/9-/12-month visits using the Functional Assessment of Cancer Therapy-Prostate (FACT­P) and European Quality of Life 5 Dimensions (EQ-5D) questionnaires. Changes from baseline and occurrence of deteriorations/improvements were compared using two-sample t-test/Mann-Whitney test and Pearson's chi-square/Fisher's exact test, respectively. Mixed-effects model for repeated measures was used to evaluate the difference between the two arms in mean changes of quality of life after 12 months. RESULTS: Frequency of clinically meaningful deterioration of quality of life assessed by FACT-P was similar for abiraterone and enzalutamide: 0%, 14.3%, 23.1%, 16.7% vs. 10%, 26.3%, 22.2%, 40% at 3-, 6-, 9- and 12 months of therapy (p=0.496, 0.670, 1.000 and 0.236, respectively). After 12 months of treatment, no statistically significant difference between the treatment arms was observed in estimated mean changes in FACT-P total scores (p=0.620) and its components, EQ-5D index (p=0.108), and EQ-5D visual analogue scale (p=0.324). CONCLUSION: According to the results of this study, abiraterone and enzalutamide had a comparable impact on quality of life in chemo-naive mCRPC in routine practice (Tab. 4, Fig. 4, Ref. 23). Text in PDF www.elis.sk Keywords: quality of life, abiraterone, enzalutamide, castration resistant prostate cancer.

The driving power of the cell cycle: cyclin-dependent kinases, cyclins and their inhibitors.

The cell cycle covers cell proliferation and growth and is strictly regulated by cyclin-dependent kinase, cyclins and their inhibitors. Cyclin-dependent kinases are serine/threonine kinases that are activated in certain phases of the cell cycle by regulatory subunits, cyclins, with which they form functional heterodimeric complexes. Under physiological conditions, the activation of cyclin-dependent kinases and cyclins is strictly controlled. The formation of these complexes is inhibited, as needed, either specifically or non-specifically, by cyclin-dependent kinase inhibitors. Progression through the cell cycle is a critical process that drives many aspects of cellular function. The cell cycle is a series of events that occurs in a repeating pattern. Each cell cycle consists of two phases, interphase and mitotic phase. Their dysregulation leads to disruption of cell cycle coordination and uncontrollable cell proliferation, which is the main feature of tumorigenesis (Fig. 1, Ref. 69). Keywords: cell cycle, regulation, cyclin­dependent kinases, cyclins, inhibitors.

The ubiquitous expression of pyruvate carboxylase among human prostate tumors.

Pyruvate carboxylase (PC) is a mitochondrial enzyme catalyzing the ATP-dependent reaction of pyruvate prolongation with bicarbonate ion to oxaloacetate. The synthesis of oxaloacetate by PC, an intermediate of the Krebs cycle, is recently recognized as a significant anaplerotic reaction that supports the biosynthetic capability, growth, aggressiveness, and even viability of several cancer cell types. PC expression was confirmed in several types of cancer cells and tumors. To evaluate the possibility that prostate tumor-forming cells are also exploiting the anaplerotic role of PC, we applied immunoblotting analysis to estimate its presence. Our results revealed that PC is present among the lysate proteins derived from prostate cancer and benign prostatic hyperplasia samples. The expression of PC in cells of prostate tumors and benign prostatic hyperplasia supposes that PC could facilitate the formation of oxaloacetate in situ and enhance the autonomy of their biosynthetic metabolism from the availability of extracellular substrates by increasing the cellular anaplerotic capability (Tab. 1, Fig. 1, Ref. 30). Keywords: pyruvate carboxylase, prostate cancer, cancer metabolism, anaplerosis.

Differential profiling of prostate tumors versus benign prostatic tissues by using a 2DE-MALDI-TOF-based proteomic approach.

Oncoproteomic technologies offer a complementary approach to the understanding of cancer proteins' function and the translation of molecular knowledge into clinical practice. Our aim was to compare the proteomic profiles of prostate tumors versus benign prostatic hyperplasia (BPH) tissues in order to identify modulated proteins as the potential biomarkers for prostate cancer. Proteins extracted from twenty prostate cancer tissue specimens and ten BPH tissues were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF mass spectrometry. Western blot and quantitative real-time PCR (RT-PCR) were performed to confirm the different amounts of protein biomarkers revealed by 2DE combined with MALDI mass spectrometry. We found 42 spots whose expression in the prostate was altered more than 1.5-fold compared with BPH tissue (p<0.05). These spots represented ten different proteins that were identified by a database search after mass spectrometry: they comprised proteins involved in the regulation of actin dynamics, the cytoskeleton, and cell motility (ACTG2, ACTA2, TPM1, DES, VIM, FLNA, and TAGLN), heat shock protein-27 (Hsp27), and proteins with other functions (TR and RANBP3). Subsequent western blot and RT-PCR assays for DES, VIM, TAGLN, and Hsp27 in prostate tumor tissues and BPH tissues confirmed the observations obtained by proteomic analysis. The cytoskeletal and cytoskeleton-associated proteins identified by this approach might be useful molecular targets for prostate cancer diagnostics and may contribute to novel therapies for prostate cancer.

Involvement of calcium regulating ion channels in contractility of human isolated urinary bladder.

This study specified the role of several key calcium-operating ion channels in contraction/relaxation of human detrusor muscle as possible target for overactive bladder (OAB) treatment. Detrusor samples, obtained from 18 males (average age 61.5 ± 5.9 years), were investigated by organ tissue bath method with following agents: diltiazem for L-type voltage-gated calcium channels; 3-fluropyridine-4-carboxylic acid (FPCA) for Orai-STIM channels; SKF 96365-hydrochloride for transient receptor potential (TRP) channels, T-type channels and Orai-STIM channels; 2- aminoethoxydiphenyl borate (2-APB) for inositol-triphosphate receptors (IP3Rs) and Orai-STIM channels. Oxybutynin and mirabegron were tested under the same conditions as controls. Mirabegron, 2-APB and FPCA exhibited the best suppressive effect on carbachol-induced detrusor contractility. As expressed by area under the contractile curve (AUCC), 2-APB, FPCA and mirabegron have similar AUCC: 1.79, 1.73, 1.73. The highest AUCC was 3.64 for diltiazem+SKF, followed by 3.21 for diltiazem, 3.16 for SKF and 2.94 for oxybutynin. The lowest median amplitude and contraction variability is for 2-APB followed by mirabegron and FPCA. There were significant differences between: 2-APB/FPCA vs.: ditiazem, diltiazem+SKF and SKF. Summary of results suggested the principal role of IP3Rs, Orai-STIM coupling and large-conductance calcium-activated potassium channels in detrusor contraction and pointed on Orai-STIM channels as possible targets for OAB pharmacotherapy.

Testosterone as a prospective predictor of pathological Gleason score and pathological stage in prostate cancer.

The aim of the study was to assess the relationship between preoperative circulating levels of total serum testosterone and pathological Gleason score and pathological stage in prostate cancer patients who underwent radical retropubic prostatectomy. The levels of total serum testosterone were measured in the morning just before surgery in a group of 201 prostate cancer patients. Multinomial logistic regression models were used to model the association between total preoperative testosterone (individually or in combination with other preoperative predictors such as age, PSA, clinical stage and biopsy Gleason score) and pathological Gleason score, pathological stage in prostate cancer patients. The association between age and total testosterone was modelled by robust regression. The total serum testosterone, in combination with other prognostic factors (age, PSA, clinical stage and biopsy Gleason score) in models, was not statistically significant predictor of pathological Gleason score and pathological stage. The highly significant relationship between age and preoperative total testosterone was observed (p = 0). In prostate cancer patients, the level of total serum testosterone increased with age. In conclusion, total testosterone is not a statistically significant predictive factor for pathological Gleason score and pathological stage.

The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes.

Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties. We hypothesized that the esophageal putative nociceptive C-fiber nerves (transient receptor potential vanilloid 1, TRPV1-positive) express multiple ASIC subunits and that the ASIC expression profile differs between the nodose TRPV1-positive subtype developmentally derived from placodes and the jugular TRPV1-positive subtype derived from neural crest. We performed single cell RT-PCR on the vagal afferent neurons retrogradely labeled from the esophagus. In the guinea pig, nearly all (90%-95%) nodose and jugular esophageal TRPV1-positive neurons expressed ASICs, most often in a combination (65-75%). ASIC1, ASIC2, and ASIC3 were expressed in 65-75%, 55-70%, and 70%, respectively, of both nodose and jugular TRPV1-positive neurons. The ASIC1 splice variants ASIC1a and ASIC1b and the ASIC2 splice variant ASIC2b were similarly expressed in both nodose and jugular TRPV1-positive neurons. However, ASIC2a was found exclusively in the nodose neurons. In contrast to guinea pig, ASIC3 was almost absent from the mouse vagal esophageal TRPV1-positive neurons. However, ASIC3 was similarly expressed in the nonnociceptive TRPV1-negative (tension mechanoreceptors) neurons in both species. We conclude that the majority of esophageal vagal nociceptive neurons express multiple ASIC subunits. The placode-derived nodose neurons selectively express ASIC2a, known to substantially reduce acid sensitivity of ASIC heteromultimers. ASIC3 is expressed in the guinea pig but not in the mouse vagal esophageal TRPV1-positive neurons, indicating species differences in ASIC expression.

The association between estrogen receptor alpha polymorphisms and the risk of prostate cancer in Slovak population.

The aim of our study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, PvuII and XbaI, on the development of prostate cancer within Slovak population, as well as their correlation with selected clinical characteristics. The study was performed using 311 prostate cancer patients and 256 healthy male controls. Both polymorphisms were significantly associated with higher risk of prostate cancer development. At the same time, the CC genotype of PvuII polymorphism (OR = 1.98; 95% CI 0.94-4.21; p = 0.05) and the AG genotype of XbaI polymorphism (OR = 1.74; 95% CI 1.0-3.02; p = 0.04) significantly contributed to the development of low-grade carcinoma, while the AG and GG genotypes of the XbaI polymorphism contributed mainly to the development of high-grade prostate cancer (OR = 1.83; 95% CI 1.12-3.01; p = 0.01 and OR = 2.13; 95% CI 1.06-4.19; p = 0.03, respectively). Similarly, the AG and GG genotypes of XbaI polymorphism showed significant association with prostate cancer in patients with serum PSA level ≥10 ng/ml. Both polymorphisms were found at the same time to be more frequent in patients diagnosed before the age of 60. We conclude on the basis of these results that PvuII and XbaI polymorphisms of estrogen receptor alpha might be associated with prostate cancer risk within Slovak population. Although this is a pilot study and, as such, more detailed investigations are needed to confirm the role of these polymorphisms in prostate cancer development and progression within said Slovak population, our results might still provide a valuable basis for further research with larger patient groups.

Polymorphisms in the gene encoding CYP1A2 influence prostate cancer risk and progression.

The role of the cytochrome P450 1A2 (CYP1A2) rs2472299, rs2470890 and rs11072508 polymorphisms in prostate cancer risk, disease progression and tumour development remains unclear. The potential associations of these three CYP1A2 polymorphisms and haplotypes with prostate cancer susceptibility and its clinicopathological characteristics were therefore investigated. The present case-control study consisted of 522 patients with prostate cancer and 554 healthy controls. High-resolution melting analysis was used to determine the CYP1A2 polymorphisms. No significant association in prostate cancer risk was seen for CYP1A2 rs2472299 and rs11072508. However, a significantly decreased risk of prostate cancer was found for CYP1A2 rs2470890 [odds ratio (OR), 0.67; P=0.02] in the recessive model. After analysis of the associations of clinical status and these three CYP1A2 polymorphisms, the CYP1A2 rs2470890 and rs11072508 polymorphisms showed a positive association with a higher Gleason score (rs2470890 OR, 1.36, P=0.04 in the allelic model; rs11072508 OR, 1.37, P=0.04 in the allelic model and OR, 1.60, P=0.03 in the dominant model). All three polymorphisms showed a significant positive association with pathological T stage in the additive, allelic and dominant genetic models (P<0.05). Haplotype analysis revealed that the most common haplotypes 'GTT' and 'ACC' were significantly associated with pathological T stages 3 and 4 (OR, 0.62; P=0.02 and OR, 1.54; P=0.03, respectively). A significant association was found between the 'GTT' haplotype and the Gleason score (OR, 0.71; P=0.03). In conclusion, these CYP1A2 polymorphisms and haplotypes have the potential to predict prostate cancer disease progression.

Effect of CYP17 and PSA gene polymorphisms on prostate cancer risk and circulating PSA levels in the Slovak population.

Cytochrome P-450c17α (CYP17) and prostate-specific antigen (PSA) genes, which are involved in the androgen metabolism cascade, have been studied as possible candidates for genetic influences on prostate cancer development. Contradictory results prompted us to evaluate the frequencies of polymorphisms in the CYP17 and PSA genes as well as the association between these genetic variants and serum PSA levels in prostate cancer patients and men routinely screened for prostate cancer with PSA in the Slovak male population. The CYP17 and PSA polymorphisms were determined by the PCR-RFLP analysis in 197 Caucasian prostate cancer patients and 256 Caucasian controls. We did not find any association between the CYP17 and PSA genotypes and prostate cancer risk overall, or by grade. Also the total serum PSA levels in the cases with the AG or AA genotype were not significantly higher than in the men with the GG genotype (P > 0.05). Our study did not provide support for the hypothesized relationship between CYP17 and PSA gene polymorphisms and prostate cancer in the Slovak male population.

Role of Genetic Variations in CDK2, CCNE1 and p27KIP1 in Prostate Cancer.

BACKGROUND/AIM: Our aim was to investigate possible influences of genetic variants in genes involved in the G1/S transition [cyclin-dependent kinase-2 (CDK2), cyclin E1 (CCNE1) and cyclin-dependent kinase inhibitor 1B (p27KIP1)] on the expression/activity of their corresponding proteins and to assess the functional impact of these variants on the risk of prostate cancer. MATERIALS AND METHODS: We genotyped 530 cases and 562 healthy controls for two relevant single nucleotide polymorphisms (CDK2 rs2069408 and CCNE1 rs997669) by TaqMan genotyping assay. p27KIP1 rs2066827 polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism assay. In addition, the expression of CDK2, CCNE1 and p27KIP1 was evaluated by quantitative real-time-polymerase chain reaction and western blotting in 44 prostate cancer tissues and 31 benign prostatic hyperplasia tissues. RESULTS: No association was found between CDK2 rs2069408, CCNE1 rs997669 or p27KIP1 rs2066827 polymorphisms and an increased risk of prostate cancer development. Higher CDK2 expression was more prevalent in those with rs2069408 GG genotype than in AA carriers (p>0.05). We also noted reduced p27KIP1 protein expression in those with the p27KIP1 G109 allele. No difference was observed for CCNE1 expression in relation to the risky genotype (CC). A significant association was detected between CCNE1 mRNA overexpression and development of higher-grade carcinomas (Gleason score >7, p<0.05). CONCLUSION: Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27KIP1 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27KIP1, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.

Competition for soil resources forces a trade-off between enhancing tree productivity and understorey species richness in managed beech forests.

Traditionally focussed on maximising productivity, forest management increasingly has to consider other functions performed by the forest stands, such as biodiversity conservation. Terrestrial plant communities typically possess a hump-back relationship between biomass productivity and plant species richness. However, there is evidence of a reverse relationship in forests dominated by beech, one of the most competitive and widespread tree species in temperate Europe. To fully explore the tree productivity-species richness relationship, we investigated above- and below-ground drivers of understorey plant species richness. We focussed on managed beech forests growing along an elevation gradient in Central Europe. We found that the lowest understorey plant diversity was under conditions optimal for beech. Tree fine root mass, canopy openness, soil C/N ratio, the interaction between tree fine root mass and stoniness, and stand structural diversity explain the variation of understorey species richness. We show that the competition for soil resources is the main driver of plant species diversity in managed forests; maximising beech growth in optimal conditions may thus come at the expense of understorey plant richness.

Trends in prostate cancer incidence and mortality before and after the introduction of PSA testing in the Slovak and Czech Republics.

AIMS AND BACKGROUND: As two neighboring countries in central Europe with national cancer registries, the Slovak (SR) and Czech Republics (CR) are countries with a medium global rate in the occurrence of prostate cancer. This paper analyzes the incidence of prostate cancer and mortality before and after the introduction of PSA testing in the two Republics and the possible reasons for any differences discovered and compares the results with selected regions and countries of the world. STUDY DESIGN AND RESULTS: In the Slovak Republic, prostate cancer incidence (age-adjusted to the world standard population) has risen from 14.6/100,000 in 1968 (95% CI, ±1.5772) to 36.2/100,000 in 2005 (95% CI, ±2.0678). The estimated annual increase in the incidence during the period 1968-1991 (before nationwide PSA testing) was 0.421; from 1991 (when nationwide PSA testing began) to up to 2003 it was 0.941. Mortality rates grew from 7.3/100,000 in 1968 to 14.9/100,000 in 2005. In spite of the geographic proximity of the two countries, the increase in incidence occurred faster in the Czech than in the Slovak Republic, from 15.8/100,000 in 1977 (95% CI, ±0.9748) to 59.5/100,000 in 2005 (95% CI, ±1.7187). The estimated annual increase in incidence in the Czech Republic for the period of 1977-1991 was 0.581. From 1991 (when national PSA testing began) until 2003, it was 1.981. In the period before 1991, mortality rose more sharply in the Czech than in the Slovak Republic, whereas after the introduction of PSA testing mortality stabilized more quickly in the Czech than in the Slovak Republic. In the Slovak Republic, a significant reduction in mortality was observed after 2002 and has continued to the present and probably is not affected only by the results connected with the increase in PSA testing. CONCLUSIONS: The difference in the incidence and mortality of prostate cancer in the Slovak and the Czech Republics results from a difference in the intensity of PSA testing as well as from the introduction of complex, more effective treatment in advanced clinical stages.

Association between estrogen receptor ß polymorphisms and prostate cancer in a Slovak population.

Sex steroid hormones have important roles in the function of the prostate; however, they may also serve as factors in the initiation and progression of carcinogenesis. Estrogens, acting through estrogen receptors, may significantly affect prostate cancer development and progression. The main aim of the present study was to analyze the association between the rs3020449, rs4986938 and rs1256049 polymorphisms in the promoter region of the estrogen receptor ß (ESR2) gene and prostate cancer risk in the Slovak population. A total of 510 patients with prostate cancer and 184 healthy men were included in the present study. No association between the rs4986938 and rs1256049 polymorphisms and prostate cancer development and progression was revealed; however, there was a statistically significant association between the rs3020449 GG genotype [odds ratio (OR), 2.35; P=0.002] and the G allele (OR, 1.42; P=0.005) and a higher risk of prostate cancer development. The rs3020449 GG genotype was significantly associated with a higher risk of development of carcinoma with a Gleason score >7 (OR, 2.66; P=0.005), as well as with the development of carcinoma with pT3/pT4 (OR, 2.28; P=0.02). According to the results from the present study, the rs3020449 polymorphism, in the promoter region of ESR2, may be considered to have a role in the development and progression of prostate cancer in the Slovak population.

Screening for the Key Proteins Associated with Rete Testis Invasion in Clinical Stage I Seminoma via Label-Free Quantitative Mass Spectrometry.

Rete testis invasion (RTI) is an unfavourable prognostic factor for the risk of relapse in clinical stage I (CS I) seminoma patients. Notably, no evidence of difference in the proteome of RTI-positive vs. -negative CS I seminomas has been reported yet. Here, a quantitative proteomic approach was used to investigate RTI-associated proteins. 64 proteins were differentially expressed in RTI-positive compared to -negative CS I seminomas. Of them, 14-3-3γ, ezrin, filamin A, Parkinsonism-associated deglycase 7 (PARK7), vimentin and vinculin, were validated in CS I seminoma patient cohort. As shown by multivariate analysis controlling for clinical confounders, PARK7 and filamin A expression lowered the risk of RTI, while 14-3-3γ expression increased it. Therefore, we suggest that in real clinical biopsy specimens, the expression level of these proteins may reflect prognosis in CS I seminoma patients.

Validation of the Slovakian version of the P-QOL questionnaire.

INTRODUCTION AND HYPOTHESIS: This study aimed to validate the Slovakian version of the prolapse quality-of-life (P-QOL) questionnaire. METHODS: The P-QOL questionnaire was translated into the Slovakian language and administered to women recruited from a urogynecology outpatient clinic at a tertiary referral teaching hospital. After completing a questionnaire, all women were examined in supine position using the Pelvic Organ Prolapse (POP-Q) Quantification system. The reliability was assessed by using a 2-week test-retest analysis. RESULTS: Fifty symptomatic and 79 asymptomatic women were included. The score of P-QOL was strongly correlated with the vaginal examination findings among the symptomatic group (p < 0.001 in eight domains). P-QOL domain scores were significantly different between symptomatic and asymptomatic women. The test-retest reliability confirmed a highly significant correlation between the total scores for each domain (p < 0.001). CONCLUSION: The Slovakian version of the P-QOL questionnaire is a valid, reliable, and easily comprehensible instrument to assess quality of life of women with uterovaginal prolapse.

Germline Mutations in DNA Repair Genes in Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: The aim of this study was to analyse the genetic profiles of metastatic castration-resistant prostate cancer (mCRPC) by using next generation sequencing to identify variants with pathogenic potential in nine DNA repair genes - BRCA1, BRCA2, RAD50, RAD51, RAD51C/D, ATM and ATR. MATERIALS AND METHODS: Isolated genomic DNA from peripheral blood of 50 patients with mCRPC was used for the sequencing of 111 genes associated with hereditary cancer on an Illumina platform. Identified variants were tested in Integrative Genomic Viewer, their clinical significance confirmed in databases and their potential impact on protein function predicted by in silico tools. RESULTS: From nine analysed DNA repair genes, we identified 14 relevant variants; three pathogenic variants - BRCA2 (rs80359306), RAD50 (rs786201531) and ATM (rs1555099760), and eleven other variants with pathogenic potential. CONCLUSION: The pathogenic variants identified in this study are located in evolutionarily conserved regions of proteins and are highly likely to affect DNA repair efficiency.

Association of MDM2 T309G (rs2279744) Polymorphism and Expression Changes With Risk of Prostate Cancer in the Slovak Population.

BACKGROUND/AIM: The aim of this study was to evaluate the relationship between MDM2 T309G polymorphism and prostate cancer risk in the Slovak population and the association of this polymorphism with MDM2 expression and clinicopathological features. MATERIALS AND METHODS: The MDM2 T309G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 506 prostate cancer patients and 592 controls. Quantitative real-time (RT)-PCR and western blot analysis were applied to examine MDM2 expression in 47 prostate cancer tissues and 43 benign prostatic hyperplasia (BPH) tissues. RESULTS: A decreased risk of prostate cancer in men carrying the GG genotype in comparison with the TT genotype was found. A decrease in the relative MDM2 mRNA and protein levels was found in prostate cancer tissues among patients with the MDM2 GG genotype. CONCLUSION: There is a potentially protective effect of the MDM2 GG genotype on the risk of prostate cancer in the Slovak male population.

Associations Between Gene Polymorphisms of Vascular Endothelial Growth Factor and Prostate Cancer.

BACKGROUND/AIM: The aim of this study was to evaluate the association between selected polymorphisms of the vascular endothelial growth factor gene (rs699947, rs144854329, rs833061, rs2010963, rs3025039) and the risk of prostate cancer development and progression. MATERIALS AND METHODS: The present study included 446 patients with prostate cancer and 241 healthy men. Genotyping was performed by polymerase-chain reaction-restriction fragment length polymorphism analysis. RESULTS: No significant association between the individual polymorphisms studied and the risk of prostate cancer development was detected. A statistically significantly increased risk of prostate cancer development associated with the presence of 9 or 10 risky alleles was found considering the whole group of patients, as well as in patients with low-grade carcinomas (Gleason score <7). CONCLUSION: Individual polymorphisms of VEGF do not appear to contribute to prostate cancer. However, a combination of risky alleles of the studied polymorphisms significantly increases the risk of prostate cancer in Slovak patients.

The Role of Interleukin-6 Polymorphism (rs1800795) in Prostate Cancer Development and Progression.

BACKGROUND/AIM: Interleukin-6 is an important modulator of inflammation, which is one of the factors involved in prostate cancer. The aim of the study was to evaluate the possible association of the IL-6 -174 polymorphism (rs1800795) with the risk of prostate cancer development and progression. MATERIALS AND METHODS: The study population consisted of 446 prostate cancer patients, 377 benign prostatic hyperplasia (BHP) patients and 276 healthy men. Genotyping was performed by PCR-RFLP analysis. IL-6 plasma levels were measured by the ELISA method. RESULTS: The GC genotype (OR=0.61, p=0.005) and C allele (OR=0.8, p=0.04) of the IL-6 -174 polymorphism were significantly associated with prostate cancer. No genotype was associated with BHP. IL-6 plasma levels were significantly increased in prostate cancer patients compared to both healthy men (p=0.02) and BHP patients (p=0.008). No significant differences were observed in IL-6 plasma levels in connection with IL-6 -174 genotypes. CONCLUSION: The IL-6 -174 polymorphism was significantly associated with prostate cancer in Slovak patients.