Prostate Cancer Risk Research Articles

Risk of subsequent primary cancers in bladder cancer survivors

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Serum uric acid and prostate cancer: findings from the NHANES (2007–2020)

BackgroundThe relationship between serum uric acid (SUA) levels and prostate cancer (PCa) remains controversial. This cross-sectional study investigated the association between SUA levels and PCa incidence.MethodsA total of 9,776 participants aged ≥40 from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2020 were included, 503 of whom had PCa. Weighted univariate logistic regression, multivariate logistic regression, and smooth-fitting curve analyses were used to analyze the association between SUA and PCa incidence. Concurrently, the fitted smoothing curves were used to explore the potential non-linear relationships. If non-linearity was observed, a recursive algorithm further calculated the inflection point.ResultsThree models were used to analyze the correlation between SUA levels and PCa incidence. All regression models demonstrated a negative correlation between SUA levels and PCa incidence (model 1: OR = 0.88, 95% CI=0.80–0.97; model 2: OR = 0.87, 95% CI=0.80–0.96; model 3: OR = 0.87, 95% CI=0.78–0.96). According to the trend test, with increasing SUA, the risk of PCa showed a downward trend (three models P for trend = 0.037, 0.015, 0.016). According to the subgroup analysis, a significant negative correlation between SUA and PCa was detected in individuals aged >60 years, non-Hispanic whites, those of other races, and those with hypertension. Moreover, the association between SUA and PCa followed a U-shaped curve among participants without hypertension, and the inflection point of SUA was 5.1 mg/dl.ConclusionsThis cross-sectional study revealed a negative relationship between SUA levels and the risk of PCa, particularly in specific demographic groups. These findings offer a fresh perspective on the role of SUA in PCa patients, potentially paving the way for new approaches for the prevention and treatment of PCa. However, further studies are necessary to validate these findings.

Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.

Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of MTM1-the phosphatase antagonist of VPS34-we show that dietary MSB improved muscle histology and function and extended life span. These findings enhance our understanding of pro-oxidant selectivity and show how definition of the pathways they impinge on can give rise to unexpected therapeutic opportunities.

Bidirectional influence between benign prostatic hyperplasia, prostate cancer, and prostatitis and mental disorders: two-sample and multivariate mendelian randomization analyses

Background We aimed to use Mendelian randomization (MR) to determine the causality between fifteen major mental disorders (MDs) and benign prostatic hyperplasia (BPH), prostate cancer (PCa), and prostatitis. Methods The main MR analysis was performed using the inverse variance-weighted (IVW) method. Results The study found that insomnia (odds ratio [OR], 1.6190; p = .0017) was significantly associated with an increased risk of BPH, and mood disorders (OR, 1.1590; p = .0221) was nominally associated with an increased risk of BPH. Conversely, BPH was suggestively associated with a low epilepsy risk (OR, 0.9988; p = .0043), and was nominally associated with an increased risk of insomnia (OR, 1.0061; p = .0291). Furthermore, attention deficit hyperactivity disorder (ADHD) was suggestively associated with a low PCa risk (OR = 0.9474; p = .0058). However, no causal relationship was observed between PCa and MDs. Finally, anorexia nervosa (OR, 1.1686; p = .0248) and depression (OR, 336.5383; p = .0308) were nominally positively correlated with prostatitis. Prostatitis was suggestively associated with increased risk of ADHD (OR, 1.0868; p = .0413). Conclusion Our findings provide clinicians with a basis for developing programs to prevent or treat MDs and prostatic diseases.

Association of biological aging with prostate cancer: insights from the National Health and Nutrition Examination Survey.

The link between biological aging and prostate cancer (PCa) risk, particularly as indicated by elevated prostate-specific antigen (PSA) levels, remains uncertain. This study utilized data from the National Health and Nutrition Examination Survey (2001-2010) to explore this association. Biological age was assessed using Klemera-Doubal method age (KDMAge) and phenotypic age (PhenoAge). PCa was identified through self-reported diagnoses, and highly probable PCa was determined by PSA levels. We analyzed the prevalence of PCa and PSA-defined highly probable PCa across quartiles of biological age measures using weighted chi-square and linear trend tests. Associations were evaluated using weighted multiple logistic regression models. Among 7,209 and 6,682 males analyzed, the overall weighted prevalence of PCa was 2.86%, increasing to 9.60% in those aged 65 and above. A significant rise in PCa prevalence was observed with higher quartiles of KDMAge or PhenoAge (P for trend < 0.001), particularly in those under 65. In this younger group, higher PhenoAge acceleration quartiles were linked to increased PCa prevalence and higher risk of PCa (OR = 1.50, P = 0.015) as well as highly probable PCa in those without a diagnosis (OR = 1.28, P = 0.031). These findings suggest that accelerated biological aging is associated with an increased risk of PCa and may indicate early risk as signaled by PSA levels, even in those without a PCa diagnosis.

Increased risk of genitourinary cancer in kidney transplant recipients: a large-scale national cohort study and its clinical implications.

To investigate the risk of genitourinary (GU) cancer in kidney transplant recipients (KTRs) compared to that in the general population, focusing on potential risk factors and clinical implications. Using a national cohort of approximately 360,000 individuals, including 31,542 KTRs, we conducted a retrospective analysis of the data from 2007 to 2018. Propensity score matching was used to compare KTRs with a healthy population, adjusting for age, sex, diabetes, hypertension, and hypercholesterolemia. We identified a significantly increased risk of GU cancers, particularly bladder and kidney cancers, in KTRs. Multivariate analysis revealed a higher risk of GU cancer associated with kidney transplantation [hazard ratio (HR) 2.133, 95% confidence interval (CI) 1.641-2.772] and hypercholesterolemia (HR 1.725, 95% CI 1.227-2.425), with older age and male sex also being significant risk factors. Conversely, no significant increase in prostate cancer risk was observed in KTRs compared to the general population. This national cohort-based study indicated an increased risk of GU cancer in KTRs, underscoring the need for targeted cancer surveillance and pre- and post-transplant counseling. These findings provide valuable insights for the development of cancer surveillance programs for KTRs and highlight the necessity for further research in this field.

The mendelian randomized study revealed the association of prostatitis with prostate cancer risk

In recent observational studies, a potential link between prostatitis and prostate cancer (PCa) has been hinted at, yet the causality remains ambiguous. In our endeavor to scrutinize the conceivable causal nexus between prostatitis and PCa, we embarked upon a Mendelian randomization (MR) study. MR circumvents arbitrary groupings by employing genetic variations that have a strong association with the exposure as instrumental variables to infer causal relationships between exposures and outcomes. The etiology of PCa remains elusive. Given that prostatitis and prostate cancer occupy the same anatomical region, MR can more effectively delineate their relationship by mitigating confounding variables. This method can indirectly elucidate disease correlations, thereby contributing to cancer prevention strategies. FinnGen Consortium data were used for the prostatitis genome-wide association study (GWAS), including 74,658 participants. UK biobank baseline data (ncase = 3436, ncontrol = 459574), European Bioinformatics Institute Database (ncase = 79148, ncontrol = 61106), and IEU openGWAS database (ncase = 79148, ncontrol = 61106) were used for PCa outcomes, mostly for European population samples. Data from the GWSAs for prostatitis were compared with data from the three GWASs for PCa, respectively, in an analysis of an MR. Utilizing the inverse variance weighting (IVW) methodology as our primary analytical framework, we delved into a meticulous exploration of the conceivable causal association between prostatitis and PCa. Furthermore, we deployed supplementary methodologies, including Maximum Likelihood, MR-Egger, weighted median, and MR-PRESSO, to thoroughly assess and scrutinize the causality aspect comprehensively. Cochran’s Q statistic is employed as a metric to quantify the heterogeneity inherent in instrumental variables. The inverse variance weighted analysis revealed no discernible effect of prostatitis on PCa in the three PCa GWAS databases (odds ratio [OR]: 1.001, 95% Confidence Interval [CI]: 0.999–1.002, p = 0.28), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40). Similarly, employing MR-Egger did not yield substantial evidence (OR: 0.999, 95% CI: 0.999–1.002, p = 0.89), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07). The weighted median analysis also failed to provide convincing support for the impact of prostatitis on the incidence of PCa (OR: 1.001, 95% CI: 1.000-1.002, p = 0.064), (OR: 0.989, 95% CI: 0.946–1.034, p = 0.64), (OR: 0.989, 95% CI: 0.945–1.036, p = 0.65). The results of the MR showed no causality from prostatitis to PCa.

Associations of prostate tumor immune landscape with vigorous physical activity and prostate cancer progression.

Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood. We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy, and 101 radiation-treated prostate cancer patients in FASTMAN. Structured questionnaires administered in UNC CSC assessed physical activity. In both studies, digital image analysis of H&E-stained tissues was applied to quantify Tumor Infiltrating Lymphocytes (TILs) in segmented regions. Nanostring gene expression profiling in UNC CSC and microarray in FASTMAN were performed on tumor tissue and a 50-gene signature utilized to predict immune cell types. Vigorous recreational activity, reported by 34 (29.1%) UNC men, was inversely associated with TILs abundance. Tumors of men reporting any vigorous activity versus none showed lower gene expression-predicted abundance of Th, exhausted CD4 T cells and macrophages. T cell subsets, including Treg, Th, Tfh, exhausted CD4 T cells, and macrophages were associated with increased risk of biochemical recurrence, only among men with ERG-positive tumors. Vigorous activity was associated with lower prostate tumor inflammation and immune microenvironment differences. Macrophages and T cell subsets, including those with immunosuppressive roles and those with lower abundance in men reporting vigorous exercise, were associated with worse outcomes in ERG-positive prostate cancer. Our novel findings contribute to our understanding of the role of the tumor immune microenvironment in prostate cancer progression, and may provide insight into how vigorous exercise could affect prostate tumor biology.

Predicting Metastasis and Mortality Risk in Prostate biopsy using genomics and biopsy related factors

Abstract Introduction/Objective Prostate cancer, the most prevalent cancer among men, is diagnosed through biopsy, yet its predictive accuracy for metastasis and mortality risk remains limited. An approach to stratifying this risk is by combining biopsy data and genetics. The Decipher genomic classifier aids in estimating such risks. This study investigates the correlation between Decipher, biopsy-related factors, and the risk of prostate cancer metastasis or mortality. Methods/Case Report 50 prostatic adenocarcinoma biopsies were analyzed. Patient age, average tumor volume in positive cores, PSA levels, and Gleason score were documented. Employing Tobit regression with maximum likelihood estimation, the study examined the link between various factors and metastasis/mortality risk of prostatic cancer. Dependent variables encompassed 5, 10, and 15-year risks, while the independent variable was patient age, positive to total core ratio, average tumor volume in positive cores, PSA level, and grade group of the prostate cancer. The model integrated three dummy variables-Grade Group 1, 3, and 4, with Grade Group 2 as reference. Coefficients gauged the distinct impact of Level 1, 3, and 4 diagnoses on outcomes relative to Level 2. Statistical significance was tested conventionally. Results (if a Case Study enter NA) Grade Group 1 (Gleason score: 3 + 3): 2.35 percentage point increase in the risk of metastasis within 10 years. 3.51 percentage point increase in the risk of mortality within 15 years. Grade Group 2 Base level for comparison with other grade groups. Grade Group 3 (Gleason score: 4 + 3): No statistically significant difference in the predicting 5 or 10 year risk of metastasis compared to Grade Group 2. No statistically significant difference in the predicting 15 year risk of mortality compared to Grade Group 2. Grade Group 4 (Gleason score: 4 + 4): 10.07 percentage point increase in the risk of metastasis within 5 years. 17.27 percentage point increase in the risk of metastasis within 10 years. 18.48 percentage point increase in the risk of mortality within 15 years. Conclusion The findings suggest combining genomics and grade group can help predict the risk of metastasis and mortality in prostate biopsy. Grade Group 4 diagnosis greatly impacts metastasis and mortality in all timeframes.While Grade Group 1 has a smaller but still significant impact on the 10 and 15 year risk of metastasis and mortality. However, Grade Group 3 diagnosis does not significantly impact the risk of metastasis in any of the timeframes considered.

Relationships of dietary habits with prostate cancer risk: results from Mendelian randomization analyses and the National Health and Nutrition Examination Survey.

Background: Prior investigations identified correlations between dietary habits and the risk of prostate cancer (PCa); however, the causative dynamics are unclear. Methods: Utilizing the Mendelian randomization (MR) framework, we investigated the causal links between dietary habits, daily nutrient intakes, and risk of PCa (79 148 cases and 61 106 controls). Exposure and outcome data were obtained from the UK Biobank and the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) consortium, respectively. Univariable and multivariable MR analyses were employed. Sensitivity analyses were performed to detect outliers, evaluate heterogeneity, and discern potential pleiotropic effects. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) database (2009-2010), we selected 1294 and 1778 men aged ≥40 years from a pool of 10 537 participants, ensuring no missing information. Regression analyses examined the associations between leafy/lettuce salad intake, daily nutrient intake, and the odds of PCa. Results: Univariable MR (UVMR) analysis reveals that the intake of pork and salad/raw vegetable correlated with an elevated PCa risk. Subsequent to confounder adjustment via multivariable MR (MVMR) analysis, a causal link was established between salad/raw vegetable intake and an increased risk of PCa (odds ratio [OR]: 1.658, 95% confidence interval [95% CI]: 1.037-2.644, P = 0.046). The analysis based on NHANES datasets demonstrated a link between leafy/lettuce salad intake and heightened odds of PCa (OR: 1.025, 95% CI: 1.003-1.049, P = 0.038). Increased daily intakes of β-carotene (original OR: 1.00006, 95% CI: 1.00001-1.00011, P = 0.024) and vitamin B1 (OR: 1.474, 95% CI: 1.104-1.967, P = 0.014) were associated with a higher likelihood of PCa. Conclusions: These MR analyses substantiate the causal nexus between salad/raw vegetable intake and PCa risk. Similarly, leafy/lettuce salad intake and the odds of PCa were significantly correlated in the cross-sectional observational study. Moreover, higher daily intakes of β-carotene and vitamin B1 were linked to an increased likelihood of PCa. These findings provide practical dietary recommendations for PCa prevention and enhance early identification and diagnosis.

Integrating Multi-Omics Data to Uncover Prostate Tissue DNA Methylation Biomarkers and Target Genes for Prostate Cancer Risk.

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. We observed significant associations for 3879 CpG sites, including 926 at novel genomic loci. Among them, DNAm levels of 80 CpG sites located at novel loci are significantly associated with expression levels of 45 neighboring genes in normal prostate tissue. Of these genes, 11 further exhibit significant associations with PCa risk for their predicted expression levels in prostate tissue. Intriguingly, a total of 31 CpG sites demonstrate consistent association patterns across the methylation-gene expression-PCa risk pathway. Our findings suggest that specific CpG sites may be related to PCa risk by modulating the expression of nearby target genes.

To Drink or Not to Drink? Investigating Alcohol’s Impact on Prostate Cancer Risk

Background/Objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed and MEDLINE, focusing on epidemiological studies, meta-analyses, cohort studies, and case–control studies. Studies evaluating alcohol consumption, prostate-specific antigen (PSA) levels, and PCa risk were included. The review also explored the roles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in alcohol metabolism. Results: The analysis reveals a complex relationship between alcohol consumption and PCa. Heavy alcohol intake is associated with an increased risk of PCa, particularly more aggressive forms, and higher mortality rates. However, studies also show weak or no association between moderate alcohol consumption and PCa. The variability in findings may be attributed to differences in alcohol types, regional factors, and study methodologies. Conclusions: The link between alcohol consumption and PCa risk is multifaceted. While heavy drinking appears to increase the risk of aggressive PCa, the overall relationship remains unclear. Further research is needed to better understand these associations and inform public health recommendations and cancer prevention strategies.

Serum glycosylated hemoglobin and prostate cancer risk: Results from a systematic review and dose-response meta-analysis

ObjectivesTo evaluate the correlation between serum glycosylated hemoglobin (HbA1c) levels and the risk of prostate cancer incidence and mortality, providing a comprehensive analysis to inform preventative and clinical strategies. MethodsA systematic review and meta-analysis was conducted including studies based on their documentation of prostate cancer incidence and mortality related to HbA1c levels, with a minimum of 3 risk-related data levels. The Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for quality assessment and risk of bias evaluation. We employed generalized least squares (GLS) to assess the linear trend within individual studies and combined these estimates using a random effects model. Additionally, we utilized a restricted cubic spline (RCS) model to investigate potential nonlinear trends. ResultsA total of 13 studies were included in the quantitative synthesis ultimately. The quantitative analysis did not find a significant association between HbA1c levels and prostate cancer incidence. However, a significant positive correlation was revealed between HbA1c levels and both cancer-specific mortality (CSM) and all-cause mortality (ACM), with a 1% increase in HbA1c levels associated with a 26% increase in CSM and a 21% increase in ACM. ConclusionThe HbA1c level is significantly associated with increased prostate cancer mortality. The results highlight the importance of considering blood sugar control in the comprehensive risk assessment for prostate cancer, particularly among the nondiabetic population.

Polygenic risk and rare variant gene clustering enhance cancer risk stratification for breast and prostate cancers

Polygenic risk score (PRS) and rare monogenic variant screening are valuable tools for predicting cancer risk and identifying individuals at high risk. Integrating both common and rare genetic variants is crucial for accurate risk assessment. However, estimating the impacts of rare variants on cancer and combining them with PRS remains challenging. Here, we analyze 454,711 exome sequencing and 487,409 array UK Biobank samples, focusing on breast and prostate cancers. We introduce an expanded PRS (EPRS) approach, yielding a systematic model for more effective risk stratification. By prioritizing and clustering genes with cancer-specific rare variants based on odds ratios and population-attributable fraction, we refine risk stratification by combining both monogenic and polygenic effects. Individuals in high-PRS groups with rare high-impact gene variants show up to 15- and 22-fold higher risk for breast and prostate cancers, respectively, compared to those in the intermediate-PRS groups without rare variants. Combined risk profiles vary across distinct rare variant clusters within the same PRS group for both cancers. Our EPRS approach enhances risk stratification for breast and prostate cancers, offering important insights for future research and potential applications to other cancer types.

Single-cell analysis reveals alternations between the aged and young mice prostates

BackgroundAging of the male prostate is an inevitable process in which the prostate undergoes hyperplasia, and this growth may lead to compression of the urethra, resulting in voiding dysfunction and associated symptoms, and an increased risk of prostate cancer. Despite the significance of prostate aging, the molecular mechanisms involved are still not fully understood.MethodsProstate split by lobes from young (2 months) and aged (24 months) mice were collected for single-cell RNA sequencing (scRNA-seq) analysis. Tissues from both anterior prostate (AP) and ventral/dorsal/lateral prostate (VDLP) were included in the study. Data analysis included unsupervised clustering using the uniform manifold approximation and projection (UMAP) algorithm to identify distinct cell types based on marker gene expression. Differential gene expression analysis was performed to identify age-related changes in gene expression across different cell types. Functional enrichment analysis was conducted to elucidate biological pathways associated with differentially expressed genes. Additionally, cellular interactions and developmental trajectories were analyzed to characterize cellular dynamics during prostate aging.ResultsThe single-cell transcriptome analysis of the mouse prostate during aging revealed heterogeneity across various cell types and their changes during the aging process. We found a significant increase in the proportion of mesenchymal and immune cells in aged mice. Our study unveiled alterations in genes and pathways associated with cellular senescence, oxidative stress, and regeneration in epithelial cells. Furthermore, we observed that basal cells may undergo epithelial-mesenchymal transition (EMT) to become mesenchymal cells, particularly prominent in aged mice. Additionally, immune cells, notably macrophages and T cells, exhibited a heightened inflammatory response in aged mice.ConclusionIn summary, our study provides a comparative analysis of the single-cell transcriptome of the aged and young mice prostates, elucidating cellular and molecular changes between the aged and young mice prostates.

Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition.

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

Plant-based diets and urological health.

Plant-based diets have grown in popularity owing to multiple health and environmental benefits. Some evidence suggests that plant-based diets are associated with benefits for urological health. In genitourinary oncology, most research has focused on prostate cancer. Clinical trial results suggest a favourable influence of healthy lifestyle modifications including plant-based diets before and after prostate cancer treatment. Epidemiological evidence shows that a diet higher in plant-based and lower in animal-based food is associated with a lower risk of aggressive prostate cancer and better quality-of-life scores than a diet with less plant-based and more animal-based food. Studies on bladder and kidney cancer are scarce, but limited data suggest that vegetarian or plant-forward dietary patterns (increased consumption of fruits and vegetables and minimizing meat) are associated with a lower risk of development of these cancers than dietary patterns with fewer fruits and vegetables and more meat. With respect to benign urological conditions, epidemiological studies suggest that plant-based dietary patterns are associated with a lower risk of benign prostatic hyperplasia and urinary tract infections than non-plant-based dietary patterns. Compared with diets high in animal-based foods and low in plant-based foods, a substantial body of epidemiological evidence also suggests that increased consumption of healthy plant-based food is associated with a lower risk of erectile dysfunction. Plant-based dietary patterns that are high in fruits and vegetables with normal calcium intake, while limiting animal protein and salt, are associated with a lower risk of kidney stone development than dietary patterns that do not follow these parameters. Overall, increasing consumption of plant-based foods and reducing intake of animal-based foods has favourable associations with multiple urological conditions.

Prostate Cancer and Obesity: Current Hypotheses and Challenges

Prostate cancer is the most common cancer diagnosed in males in the United States. Known prostate cancer risk factors include age, ethnicity, and genetic factors. There is some data suggesting that obesity is a risk factor for numerous aspects related to prostate cancer including prostate cancer development, biochemical recurrence, and prostate cancer mortality. Moreover, there may be potential therapeutic complications in the obese patient. Weight loss has also been shown to benefit the patient with prostate cancer. Finally, obesity may affect the microbiome and other molecular pathways such alterations in adipokine signaling, insulin and the insulin-like growth factor 1 pathway, and effects on the tumor microenvironment (e.g.: ectopic/periprostatic fat). The purpose of this review is to discuss the most current hypotheses on the relationship between obesity and prostate cancer across this broad spectrum of potential relationships.

Commentary: Current Status of Prophylactic Nodal Irradiation in Ultra - Hypofractionated/ Stereotactic Body Radiotherapy for High - Risk Prostate Cancer

Commentary: Current Status of Prophylactic Nodal Irradiation in Ultra - Hypofractionated/ Stereotactic Body Radiotherapy for High - Risk Prostate Cancer

12234 Gα13 Promotes Clonogenic Growth By Increasing Tolerance To Oxidative Metabolic Stress In Prostate Cancer Cells

Abstract Disclosure: D. Wu: None. W. Lim: None. X. Chai: None. V.P. Seshachalam: None. S.A. Rasheed: None. S. Ghosh: None. P.J. Casey: None. Gα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors. Analyses of tumor specimens indicate that Gα13 expression correlates with patient survival in several solid cancers. We previously reported a role for Gα13 in cell migration and invasion in prostate cancer cell lines. Interestingly, patient data supports the notion that mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason scores. Gα13 lower-expressing LNCaP cells also have lower SOD2 protein levels compared to the Gα13 higher-expressing PC3 cells. Hence, we explored the role of Gα13 in prostate tumorigenesis, and its effect on cellular processes such as cell survival and mitochondrial metabolism, in human prostate cancer cell lines PC3 and LNCaP. We stably knocked-down GNA13 expression in PC3 cells and overexpressed GNA13 in LNCaP cells. We found that Gα13 promoted anchorage-independent cell growth in PC3 and LNCaP cell lines, as assessed by soft agar colony formation, spheroid formation, and xenograft tumor growth. Whole-genome transcriptome analyses suggested that Gα13-regulated genes are functionally enriched in the mitochondria compartment and that GNA13 expression positively correlated to SOD2 transcript levels in PC3 cells. We found that silencing GNA13 sensitized PC3 cells to long-term oxidative metabolic stress when cultured in media containing non-glycolytic metabolites, namely galactose, glutamate plus malate, and succinate. Furthermore, Gα13 levels impacted the abundance of SOD2 protein in the mitochondria, as well as SOD2 promoter activity and mRNA expression. In addition, silencing GNA13 increased mitochondrial superoxide levels in PC3 cells when cultured in galactose medium, as assessed by MitoSOX staining and flow cytometry. Moreover, overexpression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent cell growth in PC3 cells. Importantly, anchorage-independent cell growth was not rescued when a catalytically-inactive SOD2(Q167A) mutant was expressed. Likewise, stable knockdown of SOD2 suppressed the effect of overexpression of Gα13 on anchorage-independent cell growth in LNCaP cells. We propose a novel biological route of Gα13-mediated anchorage-independent growth and response to oxidative metabolic stress through regulation of SOD2 expression in prostate cancer cells. Given that SOD2 protein levels correlate with prostate cancer Gleason grade, identifying the upregulated GPCRs that signal through Gα13 in prostate cancer could lead to novel preventive or therapeutic strategies. Presentation: 6/1/2024