Prostate Cancer Risk Research Articles

Multi-omics identify ribosome related causal genes methylation, splicing, and expression in prostate cancer

BackgroundUnderstanding the molecular underpinnings of prostate cancer remains a critical challenge in oncology. Ribosomes, essential cellular organelles responsible for protein synthesis, have emerged as potential regulators in cancer development. Previous studies suggest that dysfunction in ribosomal processes may contribute significantly to prostate cancer progression. We used summary-data-based Mendelian randomization (SMR) and colocalization analysis, as well as single-cell analysis, to investigate the association between ribosome-related genes and prostate cancer by integrating multi-omics.MethodIn this study, we employed a multi-omics approach integrating genomics and transcriptomics data to investigate the role of ribosome-related genes in prostate cancer. Summary-level data for prostate cancer were obtained from The Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome and FinnGen studies. SMR analyses were performed to assess the relevance of ribosomal gene-related molecular signatures to prostate cancer. We further performed colocalization analysis to assess whether the identified signal pairs shared causal genetic variants. Genes were then validated with single-cell sequencing analysis.ResultsWe identified significant causal effects of ribosome gene methylation on prostate cancer. After integrating the multi-omics data of mQTL, sQTL and eQTL, we identified two ribosomal genes, NSUN4 and MPHOSPH6. Methylation and splicing at different sites on the NSUN4 gene showed increased and decreased risks for prostate cancer, indicating complex gene regulation mechanisms. For instance, NSUN4 methylation site of cg10215817 was genetically associated with the increased prostate cancer risk (OR 1.20, 95% CI 1.10,1.30), while NSUN4 methylation site of cg00937489 was genetically associated with the decreased prostate cancer risk (OR 0.84, 95% CI 0.74,0.94); NSUN4 chr1:46341497:46344801 splicing (OR 1.11, 95% CI 1.05–1.17) were positively associated with prostate cancer risk, while NSUN4 chr1:46340919:46344801 splicing (OR 0.95, 95% CI 0.92–0.97) were negatively associated with prostate cancer risk. Expression analysis indicated significant associations between prostate cancer risk and increased expression levels of NSUN4 (OR 1.06, 95% CI 1.03–1.09; PPH4 = 0.79) and MPHOSPH6 (OR 1.07, 95% CI 1.04–1.10; PPH4 = 0.70). In-depth single-cell analysis showed that NSUN4 highly expresses in epithelial cells, while MPHOSPH6 highly expresses in myeloid cells.ConclusionThe study found that ribosome NSUN4 and MPHOSPH6 genes were associated with prostate cancer risk. This integrative multi-omics study underscores the significance of ribosome-related genes in prostate cancer etiology. By elucidating the molecular mechanisms underlying ribosome dysfunction, our research identifies potential therapeutic targets for mitigating disease progression. These findings not only enhance our understanding of prostate cancer biology but also pave the way for personalized therapeutic strategies targeting ribosomal pathways to improve clinical outcomes.

PROSTATE CANCER SCREENING IN TRANSGENDER WOMEN: WHAT DO WE EXPECT?

PROSTATE CANCER SCREENING IN TRANSGENDER WOMEN: WHAT DO WE EXPECT?

Cancer incidence in the vicinity of open landfills in Guadeloupe, French West Indies

BackgroundPeople living in the vicinity of a landfill may be exposed to a wide range of pollutants, with possible subsequent health effects, including increased risks of cancer. The aim of the present study was to explore associations between cancer incidence and proximity to the main open landfills in Guadeloupe.MethodsWe used data from the Guadeloupe cancer registry over the period from 2008 to 2017. We conducted analyses for the 18 most frequent cancer sites. We used the Besag York and Mollié model to study the association between cancer incidence and distance from a landfill, with adjustment for social deprivation.ResultsPeople who lived less than 2 km from a landfill had increased risks of ovarian and head and neck cancer. Elevated risks of pancreatic cancer, prostate cancer, lung cancer and melanoma in men, as well colon cancer and hormone receptor-negative breast cancer in women, were also observed.ConclusionA link between exposure to pollutants generated by a landfill and the risk of developing certain cancers was suggested but should be confirmed by additional studies involving a better characterization of exposure and control of potential confounders.

THE EFFECT OF A HIGH FRUCTOSE DIET ON ERECTILE FUNCTION IN BILATERAL CAVERNOUS NERVE INJURY RAT MODEL

THE EFFECT OF A HIGH FRUCTOSE DIET ON ERECTILE FUNCTION IN BILATERAL CAVERNOUS NERVE INJURY RAT MODEL

MALE GENITAL SIZE AND CLINICALLY SIGNIFICANT PROSTATE CANCER: COULD THERE BE AN ASSOCIATION?

MALE GENITAL SIZE AND CLINICALLY SIGNIFICANT PROSTATE CANCER: COULD THERE BE AN ASSOCIATION?

Adolescent cardiorespiratory fitness and risk of cancer in late adulthood: A nationwide sibling-controlled cohort study in Sweden.

Cardiorespiratory fitness has been linked to both lower and higher risks of cancer, but the evidence comes from observational analysis which may be influenced by unobserved confounders and bias processes. We aimed to examine the associations between adolescent cardiorespiratory fitness and risk of cancer in late adulthood while addressing the unknown influence of unobserved familial confounders and diagnostic bias processes. We conducted a sibling-controlled cohort study with registry linkage based on all Swedish men who participated in mandatory military conscription examinations from 1972 to 1995 and who completed standardized cardiorespiratory fitness testing. The outcomes were overall cancer diagnosis and cancer mortality, and 14 site-specific cancers (diagnosis or death), ascertained using the National Patient Register and Cause of Death Register until 31 December 2023. A total of 1,124,049 men, including 477,453 full siblings, with a mean age of 18.3 years at baseline, were followed until a median (maximum) age of 55.9 (73.5) years, during which 98,410 were diagnosed with cancer and 16,789 died from cancer (41,293 and 6,908 among full siblings respectively). In cohort analysis, individuals in the highest quartile of fitness had a lower risk of overall cancer mortality (adjusted hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.67, 0.76; P < 0.001) compared to the lowest quartile, corresponding to a standardized cumulative incidence (1-Survival) difference of -0.85 (95% CI [-1.00, -0.71]) percentage points at 65 years of age. Individuals in the highest quartile of fitness also had lower risks (HRs ranging from 0.81 to 0.49, incidence differences ranging from -0.13 to -0.32 percentage points; P < 0.001 for all) of rectum, head and neck, bladder, stomach, pancreas, colon, kidney, liver, bile ducts, and gallbladder, esophagus, and lung cancer. Yet, individuals in the highest quartile of fitness had higher risks of prostate (HR: 1.10, 95% CI [1.05, 1.16]; P < 0.001, incidence difference: 0.48 percentage points, 95% CI [0.23, 0.73]) and skin cancer (e.g., non-melanoma HR: 1.44, 95% CI [1.38, 1.50]; P < 0.001, incidence difference: 1.84 percentage points, 95% CI [1.62, 2.05]). Individuals in the highest quartile of fitness had a higher risk of overall cancer diagnosis (HR: 1.08, 95% CI [1.06, 1.11]; P < 0.001, incidence difference: 1.32 percentage points, 95% CI [0.94, 1.70]), results driven by prostate and skin cancer being the most common types of cancer. When comparing full siblings, and thereby controlling for unobserved shared confounders, the lower risk of overall cancer mortality remained (HR: 0.78, 95% CI [0.68, 0.89]; P < 0.001, incidence difference: -0.61 percentage points, 95% CI [-0.93, -0.28]), while the excess risk of prostate (HR: 1.01, 95% CI [0.90, 1.13]; P = 0867, incidence difference: 0.05 percentage points, 95% CI [-0.50, 0.60]), skin (e.g., non-melanoma HR: 1.09, 95% CI [0.99, 1.20]; P = 0.097, incidence difference: 0.40 percentage points, 95% CI [-0.07, 0.87]), and overall cancer diagnosis (HR: 1.00, 95% CI [0.95, 1.06]; P = 0.921, incidence difference: 0.04 percentage points, 95% CI [-0.80, 0.88]) attenuated to the null. For other site-specific cancers, sibling comparisons results varied, with more attenuation for melanoma, kidney, stomach, bladder, pancreas, and liver, bile ducts, and gallbladder cancer, while associations with lung, colon, head and neck, and esophagus cancer seemed to attenuate less. The findings were confirmed through an extensive set of sensitivity analyses. The main limitations of this study include the lack of inclusion of female participants, lack of data on other risk factors such as smoking, alcohol consumption, and physical activity, and only adjustment for the unobserved confounders which are shared between full siblings. Higher levels of adolescent cardiorespiratory fitness were associated with lower overall cancer mortality in late adulthood, a finding that persisted in sibling comparisons. However, the influence of unobserved familial confounding appeared to vary by cancer type and be more pronounced for cancer diagnoses than for mortality. This may suggest a need for robust causal methods to triangulate results, rather than relying on correlations alone, to better inform public health efforts.

Association between thyroid disorders and the Risk of developing prostate cancer: A systematic review and meta-analysis.

To determine the association between thyroid disorders and the Risk of developing prostate cancer. We conducted this review following the recommendations of the Cochrane Collaboration and the PRISMA Statement. From the moment to the present, we have conducted a search strategy using MEDLINE, WEB OF SCIENCE, and GOOGLE SCHOLAR. We included cohort and case-control studies that examined the relationship between thyroid disorders and the Risk of developing prostate cancer. We assessed the Risk of bias using the Newcastle Ottawa Quality Assessment scale. Meta-analysis was conducted in Review Manager 5.4.1 (Revman®). We included nine studies in the analysis. The studies included were classified into two groups: those that studied hypothyroidism and those that studied hyperthyroidism. The results showed no association between thyroid abnormalities and prostate cancer risk, with an HR of 1.05 (95% CI: 0.90-1.22). Hyperthyroidism also showed no association with an HR 1.64 (95% CI: 1.00-2.69), characterized by increased serum T4 and decreased TSH. There was also no significant association with hypothyroidism, with an HR of 0.85 (95% CI: 0.67-1.10). Thyroid disorders were not associated with the Risk of developing prostate cancer.

Diagnosis and risk stratification of PI-RADS v2.1 category 3–5 lesions using amide proton transfer imaging

ObjectivesTo explore the value of amide proton transfer-weighted imaging (APTWI) combined with apparent diffusion coefficient (ADC) and prostate-specific antigen density (PSAD) in evaluating the risk of aggressive PI-RADS v2.1 category 3–5 lesions.Materials and methodsWe retrospectively analyzed clinical and MRI features of 69 patients with prostate cancer (PCa) and 32 patients with benign prostatic lesion (BL). The PCa group was classified into Gleason Grade Groups (GG) 1 to 4 based on Gleason Score (GS). APTWI parameters, ADC, and PSAD were compared among the different groups. The receiver operating characteristic (ROC) curve and precision recall (PR) curve were used to assess the diagnostic accuracy of each parameter, and Spearman rank correlation was used to analyze the relationship between APTWI parameters and GS.ResultsAPTWI parameters and PSAD were significantly higher in the PCa group than that in the BL group, whereas ADC was significantly lower in the PCa group than in the BL group. ADC showed the highest AUC in the diagnosis of PCa, followed by PSAD and APTmin. Combined analysis showed that APTmin+ADC + PSAD exhibited the highest AUC (0.997). In the PCa group, significant differences in APTWI parameters were found among GG1 to GG4 (P < 0.001), with intra-group comparisons showing significant differences between GG1 and GG3, GG1 and GG4, GG2 and GG3, and GG2 and GG4 subgroups. The AUC of APTmean was greatest in evaluating the risk of aggressive PCa (0.948), which further increased when APTmean was combined with ADC and PSAD (0.956).ConclusionIn PI-RADS v2.1 category 3–5 lesions, APT can serve as an important biomarker for the risk stratification of PCa, and combining APT with PSAD and ADC achieves the highest diagnostic efficacy.

The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer

Prostate cancer (PCa) and Type 2 diabetes (T2D) often co-occur, yet their relationship remains elusive. While some studies suggest that T2D lowers PCa risk, others report conflicting data. This study investigates the effects of peroxisome proliferator-activated receptor (PPAR) agonists Bezafibrate, Tesaglitazar, and Pioglitazone on PCa tumorigenesis. Analysis of patient datasets revealed that high PPARG expression correlates with advanced PCa and poor survival. The PPARγ agonists Pioglitazone and Tesaglitazar notably reduced cell proliferation and PPARγ protein levels in primary and metastatic PCa-derived cells. Proteomic analysis identified intrinsic differences in mTORC1 and mitochondrial fatty acid oxidation (FAO) pathways between primary and metastatic PCa cells, which were further disrupted by Tesaglitazar and Pioglitazone. Moreover, metabolomics, Seahorse Assay-based metabolic profiling, and radiotracer uptake assays revealed that Pioglitazone shifted primary PCa cells' metabolism towards glycolysis and increased FAO in metastatic cells, reducing mitochondrial ATP production. Furthermore, Pioglitazone suppressed cell migration in primary and metastatic PCa cells and induced the epithelial marker E-Cadherin in primary PCa cells. In vivo, Pioglitazone reduced tumor growth in a metastatic PC3 xenograft model, increased phosho AMPKα and decreased phospho mTOR levels. In addition, diabetic PCa patients treated with PPAR agonists post-radical prostatectomy implied no biochemical recurrence over five to ten years compared to non-diabetic PCa patients. Our findings suggest that Pioglitazone reduces PCa cell proliferation and induces metabolic and epithelial changes, highlighting the potential of repurposing metabolic drugs for PCa therapy.Graphical

Association between single and mixed exposure to potentially toxic trace metals and the risk of prostate cancer: a case-control study in Tanzania.

Metal contamination is a major environmental concern in Tanzania, where it has been linked to an increased risk of prostate cancer. However, there have been no epidemiological studies addressing this association. The aim of this study was to investigate the association between urinarytoxic trace metals and prostate cancer. Inductively coupled plasma atomic emission spectrophotometer (ICP-AES) was employed to measure the concentrations of Pb, As, Ni, Al, and Cd in urine samples from histologically confirmed100 prostate cancer patients (n = 100) and 80 healthy controls (n = 80). The associations between individual metals and prostate cancer were assessed using unconditional logistic regression, while Bayesian kernel machine regression (BKMR) was employed to investigate the combined effects of multiple metals with adjustments of potential covariates. Cancer patients had significantly higher mean levels of Ni, Pb, and As in their urine compared to controls. In multivariable logistic models, thefindingssuggested that quartiles increase of As and Cd were positively associated with prostate cancer with ORs of 5.25 (1.33, 20.72) in Q3 for As and ORs of 2.87 (1.72, 11.52) in Q4 for Cd. The BKMR results revealed that the combined effect of five urinary metals exhibited a negative association with prostate cancer risk. In conclusion, this study offers preliminary evidence suggesting that exposure to trace metals particularly Cd and As may potentially be associated with prostate cancer. Pb and Al were found to have an inverse relationship with prostate cancer and overall metal mixture hadno impact on prostate cancer. Since the study was preliminary, these results remain to be confirmed by further large-scale studies.

Optimizing clinical risk stratification of localized prostate cancer.

To review the current risk and prognostic stratification systems in localised prostate cancer. To explore some of the most promising adjuncts to clinical models and what the evidence has shown regarding their value. There are many new biomarker-based models seeking to improve, optimise or replace clinical models. There are promising data on the value of MRI, radiomics, genomic classifiers and most recently artificial intelligence tools in refining stratification. Despite the extensive literature however, there remains uncertainty on where in pathways they can provide the most benefit and whether a biomarker is most useful for prognosis or predictive use. Comparisons studies have also often overlooked the fact that clinical models have themselves evolved and the context of the baseline used in biomarker studies that have shown superiority have to be considered. For new biomarkers to be included in stratification models, well designed prospective clinical trials are needed. Until then, there needs to be caution in interpretation of their use for day-to-day decision making. It is critical that users balance any purported incremental value against the performance of the latest clinical classification and multivariate models especially as the latter are cost free and widely available.

GLP-1 Agonist Use Among Men with Localized Prostate Cancer: A Narrative Review and Rationale for Prospective Clinical Trials.

GLP-1 Agonist Use Among Men with Localized Prostate Cancer: A Narrative Review and Rationale for Prospective Clinical Trials.

Prostate cancer and pollution: Dangerous connections.

Prostate cancer and pollution: Dangerous connections.

Targeting All Multiple Magnetic Resonance Imaging Prostate Lesions Does Not Enhance Cancer Detection: Insights from the YAU Prostate Cancer Group.

Targeting All Multiple Magnetic Resonance Imaging Prostate Lesions Does Not Enhance Cancer Detection: Insights from the YAU Prostate Cancer Group.

Association Aamong Ppolymorphisms in the Aapoptosis-Rrelated NKX3-1, Caspase-3, Caspase-9, and BCL-2 Genes and Prostate Cancer Susceptibility From 9706 Cases and 12,567 Controls.

While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis-related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive. This meta-analysis was thus developed with the goal of generating more precise estimates of the relationships between polymorphisms in four apoptosis-associated genes (NKX3-1, caspase-3, caspase-9, and BCL-2) and the risk of PCa. The PubMed, Web of Science, Google Scholar, Embase, Cochrane Library, and SinoMed (CNKI and Wanfang) databases were searched for relevant studies published through December 20, 2023, using the following keywords: "polymorphism" or "variant" and "carcinoma" or "cancer" or "tumor" and "NKX3-1," "CASP3" or "Caspase-3," "CASP9" or "Caspase-9," "BCL-2" or "B-cell lymphoma" and "prostate cancer" or "PCa" or "prostate adenocarcinoma." This approach led to the identification of 22 case-control studies related to the association between apoptosis-related gene polymorphisms and PCa susceptibility enrolling 9706 cases and 12 567 controls. Subsequent analyses revealed that the NKX3-1 rs2228013, CASP9 rs1052571, and CASP9 rs4645982 polymorphisms were associated with greater PCa risk, whereas the CASP3 rs4647603 polymorphism was associated with a risk reduction. These findings provide strong evidence for the potential contributions of polymorphisms in the apoptosis-related caspase-3, caspase-9, and NKX3-1 genes in the onset and progression of PCa.

Evaluating the association of CYP17 and SRD5A2 gene polymorphisms with prostate cancer risk: A case-control study in the male population of Jammu, India

Evaluating the association of CYP17 and SRD5A2 gene polymorphisms with prostate cancer risk: A case-control study in the male population of Jammu, India

Exposure to Per- and Polyfluoroalkyl Substances and the Risk of Prostate and Ovarian Cancer: An Epidemiologic Meta-Analysis.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants. Previous research has linked PFAS exposure to prostate and ovarian cancer risk, however, the conclusions have been inconsistent. This research purpose was to determine the relationship between PFAS exposure and prostate and ovarian cancer at the population level. We systematically reviewed three databases-PubMed, Web of Science, and Embase-for research from when these databases were established to April 15, 2024. The quality of the retrieved research was evaluated using the Newcastle-Ottawa Scale (NOS) quality measurement tool. Meta-analysis of the extracted data was conducted using Stata 18. We also conducted sensitivity and subgroup analyses, as well as Begg's and Egger's tests. Twelve publications were involved in the analysis for prostate cancer, and six were included for ovary cancer. The outcomes indicated that PFOS exposure was positively related to prostate cancer (OR: 1.13, 95% CI: 1.00-1.28), while mixed PFAS exposure was positively related to ovarian cancer (OR: 1.63, 95% CI: 1.49-1.78). The source of heterogeneity identified in the subgroup analysis was primarily attributable to variations in study design. No significant study bias was detected in the analysis. The study demonstrated an association between PFAS exposure and both prostate and ovarian cancers. Further investigation is required to clarify the underlying mechanisms and potential associations.

Updated Prostate Cancer Risk Groups by Prostate-specific Membrane Antigen Positron Emission Tomography Prostate Cancer Molecular Imaging Standardized Evaluation (PPP2): Results from an International Multicentre Registry Study.

We established prognostic nomograms incorporating prostate-specific membrane antigen (PSMA) positron emission tomography (PET) parameters standardised by Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE; PPP1). Here, we develop an updated PPP2 risk score from a large international multicentre registry study. We included 6128 prostate cancer patients who underwent PSMA-PET at 20 hospitals in Europe, USA, and Australia between 2013 and 2022. Investigator sites were split 2:1 into the development (4044 patients) and validation (2084 patients) cohorts. We created nomograms of version 2 (PPP2) based on Cox regression models with the least absolute shrinkage and selection operator penalty for overall survival (development cohort). Performance of both nomograms was measured using Harrell's C-index and calibration plots and a head-to-head comparison with the National Comprehensive Cancer Network (NCCN) risk score by receiver operating characteristic curves (validation cohort). Predictors were distant metastases (extrapelvic nodal metastases [M1a], bone metastases [M1b], and visceral metastases [M1c]), PSMA expression score, and total lesion count (visual PPP2) or total tumour volume (quantitative PPP2). C-indices (95% confidence interval) in the validation cohort were 0.80 (0.78-0.82; visual) and 0.80 (0.79-0.82; quantitative), respectively. Accuracy of both the PPP2 nomograms was superior to the NCCN risk score (n=1034, area under the curve 0.84 vs 0.76; p<0.001). The retrospective design represents a limitation of the study. PPP nomograms were improved in an international multicentre study to predict accurately the 3- and 5-yr overall survival probabilities of prostate cancer. PPP2 yielded superior accuracy to the NCCN risk score. A free software tool has been created for PROMISE and PPP2 assessments (promise-pet.org).

Identification of druggable genetic targets for prostate cancer risk based on mendelian randomization and single-cell RNA sequencing.

This study aimed to identify genetic targets linked to prostate cancer risk using advanced genetic analysis techniques. The goal was to conduct a comprehensive analysis using Mendelian Randomization (MR), colocalization, and single-cell RNA sequencing to identify druggable genes as potential therapeutic targets or diagnostic markers. The study involved selecting 2608 druggable genes by intersecting expression Quantitative Trait Loci (eQTLs) with druggable genome databases. MR analysis using prostate cancer GWAS data identified genes with causal associations to prostate cancer risk. Colocalization analysis confirmed shared genetic variants influencing both the exposure and outcome. Single-cell RNA sequencing assessed gene expression in prostate tumor cell types, while a phenome-wide association study (PheWAS) evaluated potential side effects. MR analysis identified 58 genes associated with prostate cancer risk, with 12 validated by colocalization analysis. Five genes (BAK1, ATP1B2, PEMT, TPM3, ZDHHC7) demonstrated strong colocalization, indicating potential as drug targets. Single-cell RNA sequencing revealed their enrichment in prostate tumor T cells and macrophages. PheWAS suggested minimal side effects for most, except BAK1, which was linked to increased platelet counts. This study identified several genetic targets associated with prostate cancer risk, highlighting the potential for targeted therapy. By integrating Mendelian randomization analysis, colocalization analysis, and single-cell RNA sequencing, the accuracy of target validation was improved, which may provide new directions for targeted therapy in prostate cancer.

Genetic alterations of Cyclin D-CDK4/6-INK4-RB pathway in prostate cancer

BackgroundAlterations in key cell cycle regulators are strongly linked to tumorigenesis. Therefore, we hypothesized that polymorphisms of genes encoded cyclin-dependent kinase 4 and 6 (CDK4 and CDK6), cyclin D1 (CCND1), CDK inhibitors p16INK4a and p15INK4b, as well as the retinoblastoma protein (RB), could modulate prostate cancer risk and influence the corresponding mRNA levels.Methods and resultsWe evaluated CDK4 rs2069502, CDK6 rs2285332, CCND1 rs9344, p16INK4a rs11515, p15INK4b rs3217986, and RB rs3092904 polymorphisms using TaqMan® SNP Assays in a cohort comprising 532 prostate cancer patients and 567 control subjects. Additionally, we measured the relative mRNA expression levels of genes encoding these proteins in RNA derived from 44 prostate tumor tissues and 31 benign prostatic hyperplasia (BPH) tissues using quantitative real-time PCR (qRT-PCR). No statistically significant associations were found between the CDK4 rs2069502, p16INK4a rs11515 and RB rs3092904 polymorphisms and prostate cancer risk. However, the GA genotype of CCND1 rs9344 polymorphism was significantly associated with an increased risk of prostate cancer (OR, 1.64; 95% CI, 1.23–2.20; p < 0.001). Moreover, the relative mRNA expression levels of CCND1, p15INK4b and RB were significantly lower (p<0.05) in prostate tumor tissues compared to BPH tissues. Furthermore, lower relative expression levels of CDK4 and p16INK4a mRNA were associated with elevated serum PSA levels (≥10 ng/ml; p<0.05), while reduced relative expression of p15INK4b was correlated with a higher pathological T stage (pT3/pT4; p<0.05).ConclusionsOur findings indicate that genetic alterations, including polymorphisms and/or gene expression changes in the cyclin D1-CDK4-p16INK4a/p15INK4b-RB pathway, are associated with prostate cancer risk.