GLP-1 receptor agonists are valuable therapeutic agents for managing obesity and type 2 diabetes. The link between prostate cancer and obesity was described. The modulation of incretin hormone-dependent pathways may decrease the prostate cancer aggressiveness and progression.

The purpose of this study was to review and summarize the literature on the role of GLP-1 agonists in prostate cancer.

We performed a scoping literature review of PubMed from January 2002 to February 2025. Search terms included "glucagon-peptide like 1", "incretin hormone", "GLP-1 receptor agonist", and "prostate cancer". Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included GLP-1 receptor, incretin hormones, GLP-1 receptor agonists, and their role in prostate cancer development.

77 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the role of GLP-1 receptor and it's agonists in prostate cancer biology and development. The following review aims to discuss and provide information about the role of incretin hormones in prostate cancer pathogenesis and its clinical implication in patients with prostate cancer.

Incretin hormone-dependent pathways play an important role in prostate cancer pathogenesis. Moreover, GLP-1 receptor agonists seems to be a promising therapeutical agents when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer.

Background and Aims: Asthma, overweight/obesity, and cancer are closely related major public health problems. This study aimed to investigate the interaction between asthma and overweight/obesity on the cancer risk. Methods: We analyzed data from the National Health and Nutrition Examination Survey 2005-2018. Participants ages ≥ 20 years with information on asthma status, body mass index (BMI), and cancer diagnosis were included. Multivariate logistic regression models adjusted for relevant covariates were used to examine the associations among asthma, overweight/obesity, and cancer risk. In addition, we assessed the additive interaction between asthma and overweight/obesity on the cancer risk by using measures, including the relative excess risk due to interaction (RERI), attributable proportion of interaction (AP), and synergy index (S). Results: In total, 26,320 participants met the inclusion criteria. Asthma was associated with an increased risk of cancer (odds ratio [OR] 1.37 [95% confidence interval {CI}, 1.17-1.59]), whereas overweight/obesity (BMI ≥ 25 kg/m²) was also significantly associated with an elevated cancer risk (OR 1.97 [95% CI, 1.32-2.94]). Notably, a significant interaction between asthma and overweight/obesity was observed in relation to the cancer risk (RERI 0.49 [95% CI, 0.02-0.96]; AP 0.20 [95% CI, 0.04, 0.37]; S 1.53 [95% CI, 1.01-2.32]). Conclusion: Our findings demonstrated a synergistic interaction between asthma and overweight/obesity on the cancer risk. The combined effect of asthma and overweight/obesity on the cancer risk exceeded the sum of their individual effects.

Insulin resistance and prostate cancer (PCa) association results remain controversial. However, few studies have compared the role of various non-insulin-based insulin resistance (NI-IR) indices and mean platelet volume (MPV) in PCa.

We conducted a cross-sectional study, the case group included 354 patients with PCa, and the control group included 1,498 non-PCa participants. We performed inverse probability weighting to reduce the impact of differences in baseline information between the case and control groups on results. Weighted logistic regression analysis for assessing the relationship between NI-IR indices and PCa risk. Fitting 4-point restricted cubic spline (RCS) plots to show the trend of NI-IR indices with PCa risk. The interaction between insulin resistance and platelet volume based on generalized additive model (GAM) to reveal the impact of the interaction between insulin resistance and cardiovascular risk on PCa. In the end, we performed three sensitivity analyses to verify the stability of results.

Weighted logistic regression analysis revealed that all NI-IR indices were associated with PCa. When NI-IR indices were evaluated as continuous variables, in the all variables adjusted model (model 3), the adjusted OR of ZJU index was 1.337 (95%CI: 1.296-1.379), the adjusted OR of TyG index was 5.300 (95%CI:4.208-6.675), the adjusted OR of TG/HDL-c was 1.431 (95%CI:1.335-1.534), and the adjusted OR of METS-IR was 1.129 (95%CI:1.110-1.149). When NI-IR indices were analyzed as categorical variables, also in model 3, using Q1 as reference, the adjusted OR of ZJU index in Q5 was 15.592 (95%CI:10.809-22.492), the adjusted OR of TyG index in Q5 was 7.306 (95%CI:5.182-10.301), the adjusted OR of TG/HDL-c in Q5 was 4.790 (95%CI:3.459-6.632), and the adjusted OR of METS-IR in Q5 was 9.844 (95%CI:6.862-14.121). RCS displayed that PCa risk tended to increase as the ZJU index, TyG index, TG/HDL-c, and METS-IR increased. The interaction test based on the GAM indicated that the value of the interaction between TG/HDL-c and MPV on the PCa risk was χ2 = 6.924(P = 0.009). With the increase in TG/HDL-c and the decrease in MPV, the PCa risk progressively increases. The sensitivity analysis further confirmed the robustness of the results.

NI-IR indices were associated with an increased PCa risk. The interaction between MPV and insulin resistance may further contribute to the PCa risk.

Collider bias is often considered a potential explanation when the association between obesity and disease diagnosis differs from that with disease outcome, as seen in the "obesity paradox." For prostate cancer (PCa), in particular localized PCa, an "inverse" obesity paradox has been observed, where body mass index (BMI) is negatively associated with diagnosis (hazard ratio [HR] ~0.9 per 5-kg/m2 increase), but positively associated with PCa-specific death (HR ~ 1.2). However, collider bias in this context remains unexplored.

We simulated binary disease diagnosis and outcome data, including the typically unmeasured/unknown background variable (U) that could introduce collider bias. We calculated U-unadjusted (biased) and U-adjusted (true) marginal odds ratios (OR) from a case-only analysis, and determined the bias percentage usingOR Biased - OR True / OR True × 100 $$ \left({\mathrm{OR}}_{\mathrm{Biased}}-{\mathrm{OR}}_{\mathrm{True}}\right)/{\mathrm{OR}}_{\mathrm{True}}\times 100 $$ . Similar simulations were performed for classical confounding.

Across a broad range of plausible parameter values for the PCa context, collider bias did not distort the OR of BMI on PCa death by more than 4%, equivalent to a ± 0.04 distortion in the OR estimate for continuous BMI. In comparison, classical confounding showed a higher potential for distorting BMI and PCa death associations than collider bias.

Collider bias alone is unlikely to explain the inverse obesity paradox in (localized) PCa, reinforcing some mechanistic evidence that the observed positive relationship between BMI and PCa death is real, and not a statistical artifact. This finding emphasizes the importance of exploring alternative mechanisms beyond collider bias to better understand the underlying factors driving this paradox.

Prostate cancer (PrCa) is a serious health concern for the affected people and, there is an increasing demand for a viable therapy that can address the limitations of current treatments with minimal or no adverse effects. This study aims to evaluate phytocompounds extracts of Mangifera indica as a potential therapy development for prostate cancer. Herein, molecular docking, QSAR, molecular mechanics/generalized born surface area (MM/GBSA) estimation, ADME screening, and molecular dynamics (MD) simulation were performed using the Schrodinger suite to identify 17β-hydroxysteroid dehydrogenase antagonist from Mangifera indica. The results showed that fisetin (-11.669), riboflavin (-10.918), quercetin (-10.843), gallic acid 6-phenylhexyl ester (-10.817), cianidanol (-10.608), (-)-epicatechin (-10.603), ellagic acid (-10.522), Butin (-10.124) in kcal/mol were predicted to possess greater inhibitory activities against the protein target based on their high binding energies and remarkable stability compared to the standard drug, docetaxel (-7.374 kcal/mol). Fisetin (-718.37), and riboflavin (-722.37) also have better induce fit score than docetaxel (-714.02) in kcal/mol with better pharmacokinetics profile compared to the standard drug.MD simulation over 100 ns predicts that Fisetin forms stable interactions with vital residues at the catalytic site of the protein. The observations from this study predict fisetin as a putative antagonist of 17β-hydroxysteroid dehydrogenase and should be experimentally verified as a lead compound for prostate cancer therapy.

Recent studies suggest that diet fizzy drinks may contribute to prostate cancer (PCa) development. However, the causal effects between diet fizzy drinks and PCa and whether gut microbiota (GM) act as a mediator remain unclear.

We conducted two-sample Mendelian Randomization (MR) analyses utilizing large-scale genome-wide association studies (GWAS) data from the UK Biobank, the MiBioGen consortium, and PCa-related datasets. The inverse-variance weighted (IVW) method was used to evaluate the causal effects of GM and dietary preferences on PCa risk. A mediation analysis was performed to investigate whether GM mediates the relationship between dietary factors and PCa risk.

Diet fizzy drink consumption was causally associated with reduced PCa risk (OR = 0.83, 95% CI: 0.70-0.99, P = 0.041) and decreased abundance of PCa-risk-related GM taxa (Negativicutes and Selenomonadales). Mediation analysis did not reveal a statistically significant mediation effect, with a mediation proportion of 16% (95% CI: - 0.06-0.37, P = 0.13).

Consumption of diet fizzy drinks may reduce the risk of PCa, potentially through modulation of the GM; however, further studies are required to confirm these findings and clarify underlying mechanisms.

Prostate cancer (PCa) is the second most common cancer in men globally. Its growth is driven by oxidative stress associated with inflammation, aging, and environmental factors, including diet and lifestyle. These factors contribute to multiple stages of PCa progression, including progression to castration-resistant prostate cancer (CRPC). Therefore, oxidative stress represents an intriguing target for PCa chemoprevention and treatment. In vivo experimental models are crucial for understanding the mechanisms of PCa development, validating chemopreventive and therapeutic approaches, and translating preclinical results into clinical applications. We established a transgenic rat for adenocarcinoma of the prostate (TRAP) model, a transgenic rat that efficiently develops androgen-dependent adenocarcinoma, pathologically and biologically mimicking human PCa progression, to clarify the mechanisms of tumor progression, including the involvement of oxidative stress, and established a system for screening the chemopreventive effects of agents against PCa. Additionally, we derived a CRPC model from the TRAP model and developed a distant metastasis model, providing a comprehensive multistage rat model of prostate carcinogenesis. This review presents findings on the molecular mechanisms of PCa and the chemopreventive effects of natural compounds with antioxidant properties, such as polyphenols. We additionally described the potential for repositioning existing drugs with antiandrogenic activity for PCa chemoprevention.

Several studies indicated that prostate cancer has a hereditary component. In particular, a significant risk of prostate cancer has been linked to a tight familial lineage. However, to provide insight into how prostate cancer is inherited, characterising its genetic profile is essential. The current body of research on the analysis of genetic mutations in prostate cancer was reviewed to achieve this. This paper reports on the effects and underlying processes of prostate cancer that have been linked to decreased male fertility. Many research approaches used have resulted in the discovery of unique inheritance patterns and manifest traits, the onset and spread of prostate cancer have also been linked to many genes. Studies have specifically examined Androgen Receptor gene variants about prostate cancer risk and disease progression. Research has shown that genetic and environmental variables are important contributors to prostate cancer, even if the true origins of the disease are not fully recognised or established. Researchers studying the genetics of prostate cancer are using genome-wide association studies more and more because of their outstanding effectiveness in revealing susceptibility loci for prostate cancer. Genome-Wide Association Studies provides a detailed method for identifying the distinct sequence of a gene that is associated with cancer risk. Surgical procedures and radiation treatments are 2 of the treatment options for prostate cancer. Notwithstanding the compelling evidence shown in this work, suggests that more research must be done to detect the gene alterations and the use of genetic variants in the treatment of prostate cancer.

Periprostatic adipose tissue (PPAT) contributes to the pathogenesis of prostate cancer. The purpose of this study was to review and summarize the literature on the role of PPAT in prostate cancer pathogenesis. Moreover, we evaluated the clinical implication of PPAT in patients with prostate cancer. We performed a scoping literature review of PubMed from January 2002 to November 2024. Search terms included "periprostatic adipose tissue", "adipokines", and "prostate cancer". Secondary search involved reference lists of eligible articles. The key criterion was to identify studies that included PPAT, adipokines, and their role in prostate cancer biology and clinical features. In total 225 publications were selected for inclusion in this review. The studies contained in publications allowed us to summarize the data on the pathogenesis of PPAT as a contributor to prostate cancer biology and its aggressiveness. The review also presents new research directions for PPAT as a new target for the treatment of prostate cancer. Based on the current review, it can be stated that PPAT plays an important role in prostate cancer pathogenesis. Moreover, PPAT seems to be a promising target point when it comes to finding new therapies in patients with more aggressive and/or advanced stages of prostate cancer.

Predictive value of metabolic syndrome for prostate cancer risk is not clear. We aimed to assess the association between metabolic syndrome and its components with prostate cancer incidence. The primary outcome was prostate cancer incidence, i.e., incidence rate ratios and adjusted cumulative incidence curves derived from flexible parametric survival models. Adjusted cumulative incidence curves were derived using a flexible survival parametrical modeling framework. We analysed UK Biobank data including 242,349 adult males, recruited during 2006-2010 and followed up until 2021, during which 6,467 (2.7%) participants were diagnosed with prostate cancer. Our findings indicate that metabolic syndrome, as a whole, was not associated with prostate cancer risk (incidence rate ratios, 1.07; 95% confidence interval, 0.94-1.22). However, specific components such as hypertension and obesity increased the risk (incidence rate ratios, 1.22; 95% confidence interval, 1.03-1.44 and incidence rate ratios, 1.24; 95% confidence interval, 1.05-1.46, respectively). Other components, such as prediabetes/diabetes and low cholesterol, were associated with a reduced risk (incidence rate ratios, 0.80; 95% confidence interval, 0.67-0.94 and incidence rate ratios, 0.82; 95% confidence interval, 0.69-0.97, respectively), while hyperlipidaemia showed no significant effect (incidence rate ratios, 1.07; 95% confidence interval, 0.93-1.24). Further research is needed to understand the underlying mechanisms behind these relationships. Prostate cancer prevention strategies might benefit from targeting modifiable risk factors, particularly hypertension and obesity.

The objective of this study was to evaluate whether morphological (linear measurements) and functional (ADC value) assessments of periprostatic fat can predict the aggressiveness of prostate cancer (PCa) over a 5-year follow-up period.

This retrospective study included patients with histologically proven PCa who underwent 3.0T MRI between July 2016 and June 2018. Clinical and demographic data collected included PSA, PSA density (dPSA), ISUP grade, clinical and pathological staging, and treatment details. MRI-derived parameters were assessed by an experienced radiologist, who measured subcutaneous and periprostatic fat thickness, and calculated ADC values from ROI plots in periprostatic fat. Clinical and MRI parameters were analyzed for associations with biochemical recurrence, systemic metastasis, and PCa-related mortality.

After applying exclusion criteria, 109 patients were included. Using the Cox model, dPSA (p<0.01), systemic disease at diagnosis (p<0.01), and mean ADC (p<0.02) were independent predictors of overall survival (OS). For progression-free survival (PFS), only dPSA (p<0.01) and systemic disease at diagnosis (p<0.01) were significant predictors. In the Poisson Model for systemic recurrence risk, dPSA had a relative risk (RR) of 1.04 (95%CI 1.0-1.07, p=0.03), systemic disease at diagnosis had an RR of 63.3 (95%CI 3.7-86.4, p<0.01), and average ADC had an RR of 3.42 (95%CI 1.52-7.69, p<0.01).

The ADC value of periprostatic fat may serve as an additional tool for PCa risk stratification, correlating with poorer outcomes such as systemic recurrence and overall survival. If validated by external, prospective, multicenter studies, these findings could impact future therapeutic decisions.

This study aims to examine the correlation between four distinct Epstein-Barr virus (EBV) antibodies (EA-D, EBNA-1, VCA-p18, and ZEBRA) and the likelihood of developing prostate cancer (PCa) using the Mendelian Randomization (MR) technique. The primary objective is to determine whether a causal relationship exists between these EBV antibodies and prostate cancer.

Genome-wide association study (GWAS) data for EBV antibodies were sourced from the UK Biobank cohort, and prostate cancer data were obtained from the PRACTICAL consortium, which includes 79148 cases and 61106 controls. Univariable Mendelian Randomization (MR) analysis was conducted to evaluate the associations, while reverse Mendelian Randomization was employed to assess causality. Additionally, Multivariable Mendelian Randomization analysis was performed to identify independent risk factors.

Univariable MR analysis revealed significant associations between EBV EA-D (OR = 1.084, 95% CI = 1.012-1.160, IVW_P = 0.021) and EBNA-1 (OR = 1.086, 95% CI = 1.025-1.150, IVW_P = 0.005) antibodies and an increased risk of prostate cancer. Reverse MR analysis did not establish a causal relationship. Multivariable MR analysis identified the EBV EBNA-1 antibody as an independent risk factor for prostate cancer (OR = 1.095, 95% CI = 1.042-1.151, IVW_P = 0.00036).

The study highlights the association between EBV antibody levels, particularly EBNA-1, and prostate cancer risk, suggesting EBNA-1 as an independent risk factor. Future research is needed to elucidate the biological pathways linking EBV antibody levels to prostate cancer. These insights could be instrumental in developing targeted prevention strategies and therapeutic interventions for prostate cancer.

Prior studies testing the association between insulin resistance (IR) and prostate cancer (PC) risk are inconsistent. We examined the association between Homeostatic Assessment of Insulin Resistance (HOMA-IR; calculated from fasting baseline insulin and glucose) and PC in REDUCE, a 4-year randomized trial of dutasteride vs. placebo for PC prevention.

All patients had prestudy negative biopsies and underwent study mandated biopsies at 2 and 4 years regardless of prostate-specific antigen. Multivariable logistic regression models were used to investigate the associations between log-transformed or categorized HOMA-IR scores and PC risk. Multinominal regression was used to assess associations between HOMA-IR scores and tumor grade (low grade [grade group 1]; high-grade [grade groups 2-5]).

Among 5430 REDUCE participants (1212 with PC; 856 low- and 356 high-grade), higher HOMA-IR was associated with lower PC risk (log-HOMA-IR: OR, 0.89; 95% CI, 0.80-0.99; p = .03; categorized HOMA-IR: p-trend = .04). When stratified by grade, HOMA-IR was significantly associated with reduced low-grade PC risk (log-HOMA-IR: OR, 0.84; 95% CI , 0.74-0.94; p = .003; categorized HOMA-IR: p-trend = .002) but was unrelated to high-grade PC (log-HOMA-IR: OR, 1.02; 95% CI, 0.86-1.21; p = .81; categorized HOMA-IR: p-trend = .26). Results were similar in placebo and treatment arms.

In summary, higher HOMA-IR was associated with a reduced risk of low-grade PC but was not associated with high-grade disease. The mechanisms to explain these findings are unclear.

Urological tumors are an important disease affecting global human health, and their pathogenesis and treatment have been the focus of medical research. With the in - depth study of microbiomics, the role of the microbiome in urological tumors has gradually attracted attention. However, the current research on tumor - associated microorganisms mostly focuses on one type or one site, and currently, there is a lack of attention to the microbiome in the immunity and immunotherapy of urological tumors. Therefore, in this paper, we systematically review the distribution characteristics of the microbiome (including microorganisms in the gut, urine, and tumor tissues) in urologic tumors, the relationship with disease prognosis, and the potential mechanisms of microbial roles in immunotherapy. In particular, we focus on the molecular mechanisms by which the microbiome at different sites influences tumor immunity through multiple "messengers" and pathways. We aim to further deepen the understanding of microbiome mechanisms in urologic tumors, and also point out the direction for the future development of immunotherapy for urologic tumors.

Increasing number of studies suggested that environmental deleterious impacts (such as estrogen-like endocrine disruptors, EDCs, unhealthy diet) during early human development affect the risk of developing non-communicable diseases including prostate cancer (PCa) later in life. To test if the combination of EDCs and unhealthy induces adult prostate lesions, we developed an experimental model of adult male Sprague Dawley rats exposed during gestation (from day 7) to weaning to high fat diet (HFD 60 % fat), or to a xenoestrogen (estradiol benzoate, EB, 2.5 µg/d) from post-natal days 1-5, or to a combination of both. EB and EB+HFD exposures induced decreased prostate weight in adult rats along with inflammatory status. A white blood cell infiltrate was observed after EB exposure and more dramatic lesions were observed with the combined exposure, along with a gland destruction. The lesions, following EB or EB+HFD exposure, are associated with elevated mRNA levels for TNFa, IL6 and CCL2/MCP1 pro-inflammatory cytokines while the levels of the anti-inflammatory IL10 cytokine remained unchanged. This activation of NLRP3 and elevated levels of CASP1 were observed following EB or EB+HFD exposures associated with elevated mRNA levels for IL1b, substrates for the NLRP3 complex. HFD exposure alone has mild if not pro-inflammatory effects in adult prostate. In conclusion, we showed that developmental combined exposure to EB and HFD programmed prostate inflammatory lesions in adult prostate. Since proliferative inflammatory atrophy and chronic inflammation of prostate may drive cell to become cancer cells, our model might be useful for study onset of PCa.

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.

Several blood markers of inflammation are elevated in prostate cancer (PCa) and have prognostic value. Little is known about the relationship between these markers, PCa, and other factors associated with chronic inflammation, such as smoking and obesity. We analyzed the interaction between neutrophil and platelet counts indexed to lymphocyte count (NLR and PLR, resp.) and clinically significant PCa (csPCa), accounting for the potential confounding factors of systemic inflammation.

NLR and PLR were evaluated in a multicenter prospective study in 443 patients. CsPCa was defined as a Gleason ≥ 4 + 3. Differences between patients with csPCa and non-csPCA were evaluated using the chi-square test, analysis of variance or the Kruskal-Wallis test. Multivariable logistic regression analysis adjusted for smoking, hypertension, diabetes, and cardiovascular disease, and in separate models, either body mass index or waist-to-hip ratio was used to characterize the relationship between inflammation and csPCa.

None of the factors such as plateletcrit, NLR, and PLR were significantly different between patients with csPCa or non-significant PCa. After adjustment, there was no association between PLR, NLR, plateletcrit or platelet count and csPCa. In an exploratory analysis, there was no association between markers of inflammation and PSA levels > 10 ng/mL. When testing different NLR cutoffs to predict csPCa in ROC analysis, none reached a clinically meaningful value.

In contrast to previous studies, we found no significant association between easily available blood markers of inflammation and indices of PCa aggressiveness. Further research is required to determine whether inflammation promotes PCa. (ClinicalTrials.gov: NCT03127631. Date of registration: April 25, 2017.

Adenocarcinoma is the most common subtype of prostate cancer. Prostatic urothelial carcinoma (UC) typically originates from the prostatic urethra. The concurrent occurrence of adenocarcinoma and UC of the prostate gland is uncommon.

We present the case of an 82-year-old male patient with simultaneous adenocarcinoma and UC of the prostate gland. The patient underwent a transrectal ultrasound-guided biopsy, and the pathology test revealed UC. Subsequently, transurethral laser prostatectomy was performed, and the pathology test indicated adenocarcinoma of the prostate with a Gleason score of 3 + 4 and high-grade UC. Therefore, the patient was treated with androgen deprivation therapy, systemic chemotherapy, and immunotherapy. Magnetic resonance imaging performed during follow-up revealed a prostate tumor classified as cT2cN1M0, stage IVA. Therefore, the patient underwent robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection. The final pathology test of the prostate gland revealed acinar-type adenocarcinoma, Gleason pattern 4 + 3, pT2N0M0, and high-grade UC. The patient regularly presented to the clinic for postoperative follow-up evaluations. He did not experience any urinary discomfort.

According to our literature review, this is the first reported case of coexisting adenocarcinoma and UC of the prostate gland.

Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model ( n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [ γ -H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

Tumorigenesis is a multistep process, with oncogenic mutations in a normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic mutations and clonal expansion in normal tissues, their transformation into cancer remains a rare event, indicating the presence of additional driver events for progression to an irreversible, highly heterogeneous, and invasive lesion. Recently, researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution, independently of inducing mutations. Additionally, clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into tumors. However, the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully understood. In this review, we summarize the genetic, epigenetic, and external driver events, and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution. A deeper understanding of the earliest molecular events holds promise for translational applications, predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some studies have examined the relationship between diabetes mellitus and the risk of prostate cancer, there is still some debate on the matter. This study aims to carefully assess the relationship between prostate cancer and diabetes from both real-world and genetic-level data.

This meta-analysis was conducted following the PRISMA 2020 reporting guidelines. The study searched three databases including Medline, Embase and Cochrane. The studies about the incidence risk of prostate cancer with diabetes mellitus were included and used to evaluate the association. The odds ratio (OR), risk ratio (RR) and 95% confidence intervals (95% CI) were estimated using Random Effects models and Fixed Effects models. Mendelian randomization study using genetic variants was also conducted.

A total of 72 articles were included in this study. The results showed that risk of prostate cancer decreased in diabetes patients. And the influence was different in different regions. This study also estimated the impact of body mass index (BMI) in the diabetes populations and found that the risk decreased in higher BMI populations. The MR analysis found that diabetes mellitus exposure reduced the risk of prostate cancer in the European population and Asia populations. Conclusions The diabetes mellitus has a protective effect on prostate cancer. And the influence of obesity in diabetes mellitus plays an important role in this effect.

Abdominal obesity, especially visceral fat, may have negative effects on the development and progression of prostate cancer (PCa). A body shape index (ABSI) can more accurately measure visceral fat accumulation. This study aimed to investigate the association between ABSI and PCa in US adults.

11,013 participants were enrolled in the National Health and Nutrition Examination Survey from 2001 to 2018. Weighted multivariate logistic regression analyses were employed to explore the independent relationship between ABSI and PCa. Moreover, restricted cubic spline (RCS) analysis, subgroup analysis, and interaction tests were performed.

ABSI was positively associated with the presence of PCa. When comparing the second, third, and fourth ABSI quartile to the lowest quartile, the adjusted odds ratios (95% confidence intervals) for PCa risk were 1.34 (0.77, 2.31), 1.75 (1.03, 3.00), and 1.91 (1.12, 3.27), respectively (p for trend = 0.011). The restricted cubic spline regression analysis did not reveal a non-linear correlation between ABSI and PCa (p for non-linearity = 0.076). Subgroup analysis showed a significant interaction effect in subgroups of different BMI (p for interaction = 0.01).

Elevated ABSI is significantly associated with an increased risk of PCa, particularly among individuals who are under/normal weighted or obese.

The relationship between obesity, sexual behavior, and prostate cancer (PCa) has been widely debated, contributing to a lack of understanding of its potential mechanisms and hindering the development of effective prevention measures.

The aim of this study was to examine the causal effect of body mass index (BMI), age at first sexual intercourse (AFS), and bioavailable testosterone levels on PCa while also quantifying the potential roles of mediators.

We conducted a Mendelian randomization (MR) study using summary statistics from genome-wide associations of BMI (152,893 European males), AFS (182,791 European males), bioavailable testosterone (184,205 European males), and PCa (79,148 cases, 61,106 controls, European ancestry). Inverse-variance weighted method, weighted median method, MR-Egger regression, Least Absolute Shrinkage and Selection Operator (LASSO), and outlier test were used for MR analyses. Reverse MR and mediation analysis were performed. Data analyses were conducted from December 2022 to July 2023.

The results showed that genetic liability to BMI was protective of PCa (OR, 0.82; 95% CI: 0.74-0.91; P = 3.29 × 10-4). Genetic liability to later AFS (OR, 1.28; 95% CI: 1.08-1.53; P = 5.64 × 10-3) and higher bioavailable testosterone levels (OR = 1.11, 95% CI: 1.01-1.24, P = 0.04) were associated with an increased risk of PCa. All of these potential causal effects could only be forwarded and were not affected by prostate specific antigen (PSA) screening. After controlling for bioavailable testosterone levels, the causal impact of BMI and AFS on PCa was no longer significant. The mediation analysis suggested that the causal influence of AFS/BMI on PCa relied on bioavailable testosterone levels.

In conclusion, the difference between the univariable and multivariable MR results suggested that the causal influence of BMI and AFS on PCa relied on bioavailable testosterone levels. Further work is needed to identify other risk factors and to elucidate the specific mechanisms that underlie this causal pathway.

Studies of excess weight and weight changes throughout adult life for prostate cancer (PCa) risk and prognosis have shown inconsistent results.

In a population-based cohort, the Prostate Cancer Study throughout life (PROCA-life), 16,960 healthy men from the prospective cohort Tromsø Study (1994-2016) were included. Body mass index (BMI) and weight were measured at all four attendings, and weight change was calculated as the difference between the first and last of either Tromsø4, Tromsø5 or Tromsø6. Overall, 904 men developed PCa during 16 years of follow-up, and Poisson regression with fractional polynomials was used to investigate trends in incidence. Cox proportional hazard and logistic regression models were used to study associations between measurements of BMI and weight change and PCa risk, severity, and mortality.

At study entry, 46% of the participants (median age 44 years) were overweight, and 14% were obese (BMI > 30 kg/m2). We observed a 127% increase in overall age adjusted PCa incidence in the cohort during 1995 through 2019. No overall associations between BMI or weight change and PCa risk were observed. However, in sub-group analysis, weight gain among obese men was associated with a three-fold higher PCa risk (HR 3.03, 95% CI 1.39-6.58) compared with obese men with stable weight. Overweight was associated with lower risk of metastatic cancer (OR 0.48, 95% CI 0.30-0.75) at diagnosis. Men with obesity had higher risk of PCa-specific death (HR 1.72, 95% CI 1.03-2.88), while nonsmoking obese PCa cases had two times higher PCa-specific mortality compared with normal weighted PCa cases (HR 2.10, 95% CI 1.11-3.70).

In our cohort, weight gain among obese men was associated with higher risk of PCa, and obesity was associated with higher PCa-specific mortality, especially among nonsmokers. The relationship between weight and risk for PCa remains complicated, and future studies are needed to determine clinical implications.

Androgen receptor (AR) is known to play a crucial role in the development and progression of prostate cancer, and compounds that inhibit its activity are regarded as promising for the development of drugs to treat the disease. This study aimed to investigate the AR-inhibiting potential of Citrullus lanatus fruit compounds for prostate cancer drug development. Following HPLC identification, the binding energies, molecular interactions, and pharmacological potentials of the compounds against AR were elucidated using in silico techniques such as, molecular docking, induced-fit docking, molecular dynamics simulation, and ADMET prediction. Some of the compounds found to be present in Citrullus lanatus fruit included flavonoids such as proanthocyanin, naringin, flavan 3 ol, flavonones, naringenin, epicatechin, citrulline, and catechin. Naringenin exhibited the highest docking score in the molecular docking analysis, followed by resveratrol, ribalinidine, and epicatechin. These compounds share a common AR binding site with the standard ligand, dihydrotestosterone (DHT). Some of the compounds showed favorable ADMET profiles, while others showed at least one toxicity potential. The induced-fit docking of naringenin with AR yielded a higher docking score than the initial score obtained from standard docking while preserving stable molecular contacts with the interacting amino acids. Consistent hydrogen bond interactions of naringenin with PHE 764, ASN 705, and THR 877 of AR, including a persistent pi-pi stacking contact with PHE 764, were observed from the molecular dynamic simulation. The Citrullus lanatus compounds, particularly naringenin, may therefore be considered for further research towards the development of drugs for prostate cancer therapy.

African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia.

We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics.

No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03).

Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Cancer risk is associated with the widely debated measure body mass index (BMI). Fat mass and fat-free mass measurements from bioelectrical impedance may further clarify this association. The UK Biobank is a rare resource in which bioelectrical impedance and BMI data was collected on ~ 500,000 individuals. Using this dataset, a comprehensive analysis using regression, principal component and genome-wide genetic association, provided multiple levels of evidence that increasing whole body fat (WBFM) and fat-free mass (WBFFM) are both associated with increased post-menopausal breast cancer risk, and colorectal cancer risk in men. WBFM was inversely associated with prostate cancer. We also identified rs615029[T] and rs1485995[G] as associated in independent analyses with both PMBC (p = 1.56E-17 and 1.78E-11) and WBFFM (p = 2.88E-08 and 8.24E-12), highlighting splice variants of the intriguing long non-coding RNA CUPID1 (LINC01488) as a potential link between PMBC risk and fat-free mass.

Background: The Prostate Cancer-Patient Empowerment Program (PC-PEP) is a six-month daily home-based program shown to improve mental health and urinary function. This secondary analysis explores weight loss in male PC-PEP participants. Methods: In a randomized clinical trial with 128 men undergoing curative prostate cancer (PC) treatment, 66 received 'early' PC-PEP, while 62 were assigned to the 'late' waitlist-control group, receiving 6 months of standard-of-care treatment followed by 6 months of PC-PEP. PC-PEP comprised 182 daily emails with video-based exercise and dietary (predominantly plant-based) education, live online events, and 30 min strength training routines (using body weight and elastic bands). Weight and height data were collected via online surveys (baseline, 6 months, and 12 months) including medical chart reviews. Adherence was tracked weekly. Results: No attrition or adverse events were reported. At 6 months, the early PC-PEP group experienced significant weight loss, averaging 2.7 kg (p < 0.001) compared to the waitlist-control group. Weight loss was noted in the late intervention group of PC-PEP, albeit less pronounced than in the early group. Early PC-PEP surgery patients lost on average 1.4 kg (SE = 0.65) from the trial's start to surgery day. High adherence to exercise and dietary recommendations was noted. Conclusions: PC-PEP led to significant weight loss in men undergoing curative prostate cancer treatment compared to standard-of-care.

Allopurinol is gout medication that inhibits uric acid formation. Its possible anti-carcinogenic properties have been under research in past years. Studies based on Taiwanese registries showed that long term allopurinol use might reduce prostate cancer (PCa) incidence. However, our studies based on Finnish registries did not support those findings. In this study, we evaluate whether allopurinol use is associated with prostate cancer-specific survival (CSS) or overall survival (OS) in a Finnish population-based cohort.

The study cohort was originally enrolled for the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). We included all newly diagnosed PCa cases during 1996-2015, 9252 men in total. Information on allopurinol purchases was from the national prescription registry of the Social Insurance Institution of Finland. Information about deaths, treatments, and use of other medications was obtained from registries, and tumor stage and PSA at diagnosis from medical records. Follow-up started at diagnosis, and we analysed separately two endpoints: PCa-specific death and overall death. We used an extended Cox regression with adjustment for age at diagnosis, Charlson comorbidity index, FinRSPC trial arm, use of other drugs and EAU PCa risk group.

During a median follow-up of 9.86 years, 2942 deaths occurred, including 883 from PCa. There was no difference in CSS between allopurinol user and non-users, but allopurinol users had lower OS (multivariable-adjusted hazard ratio 1.77; 95% CI: 1.57-2.00). However, this decrease in OS was mitigated along with increasing intensity of allopurinol use.

We found no marked difference in CSS by allopurinol use. Allopurinol users had lower OS but there were no significant differences by duration or intensity of allopurinol use. Allopurinol use may not have anticancer effects against prostate cancer; instead, it may be a surrogate for metabolic problems causing shorter OS among men with PCa.

Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.

We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.

In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.

Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.

We previously reported that outcomes after radical prostatectomy (RP) were similar among non-Hispanic Black, non-Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP.

Analysis included men in SEARCH cohort who underwent RP (1988-2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration-resistant PC (CRPC), and PC-specific mortality (PCSM).

Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings.

In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post-treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research.

In recent years, triglyceride-glucose index (TyG) was a new indicator of insulin resistance, and it has been widely reported that it may be associated with serum prostate-specific antigen (PSA) concentrations.

We intended to investigate the possible connection between serum PSA concentration and the TyG index.

This is a cross-sectional study of adults with complete data on TyG and serum PSA concentrations (ng/ml) from the NHANES, 2003-2010. The TyG index is obtained by the formula below: TyG = Ln [triglycerides (mg/dL) × fasting glucose(mg/dL)/2]. Multivariate regression analysis and subgroup analysis were used to examine the connection between the TyG index and serum PSA levels.

Multiple regression analysis of the weighted linear model showed that individuals with a higher TyG index had lower PSA levels. Subgroup analyses and interaction tests showed no apparent dependence on age, race/ethnicity, BMI, household income ratio, education level, and marital status on this negative association (all interactions p > 0.05).

TyG index is related to lower serum PSA concentrations in adult men from the USA. Further comprehensive prospective studies are needed to confirm our findings.

The food products derived from Olea europaea are a fundamental part of the Mediterranean diet, and their health-promoting effects are well known. In this study, we analyzed the phytochemical characteristics, the redox state modulatory activity, and the cytotoxic effect of an olive leaf aqueous extract enriched by macroporous resin on different tumor and normal cell lines (LNCaP, PC3, HFF-1). HPLC-DAD analysis, the Folin-Ciocalteu and aluminum chloride methods confirmed the qualitatively and quantitatively high content of phenolic compounds (130.02 ± 2.3 mg GAE/g extract), and a DPPH assay (IC50 = 100.00 ± 1.8 μg/mL), the related antioxidant activity. The biological investigation showed a significant cytotoxic effect, highlighted by an MTT test and the evident cellular morphological changes, on two prostate cancer cell lines. Remarkably, the extract was practically non-toxic on HFF-1 at the concentrations (100, 150, 300 µg/mL) and exposure times tested. Hence, the results are selective for tumor cells. The underlying cytotoxicity was associated with the decrease in ROS production (55% PC3, 42% LNCaP) and the increase in RSH levels (>50% PC3) and an LDH release assay (50% PC3, 40% LNCaP, established necrosis as the main cell death mechanism.

Obesity and cancer have been found to have a direct link in epidemiological studies. Obesity raises the risk of cancer and associated chronic disorders. Furthermore, an imbalance of adipokines, like leptins, plays a crucial role in neoplasm pathogenesis, cell migration, and thereby, cancer metastasis. Also, leptin increases human epidermal growth factor receptor 2 (HER2) protein levels through the STAT3-mediated (signal transducer and activator of transcription) upregulation of heat shock protein (Hsp90) in breast cancer cells. It has been noticed that insulin and insulin-like growth factors (IGFs) act as mitosis activators in the host and cancerous breast epithelial cells. The condition of hyperinsulinemia explains the positive association between colorectal cancer and obesity. Furthermore, in prostate cancer, an alteration in sex hormone levels, testosterone and dihydrotestosterone, has been reported to occur, along with increased oxidative stress, which is the actual cause of the tumors. Whereas, there have been two interconnected factors that play a crucial role in the psychological cycle concerned with lung cancer. The review article focuses on all the prospects of etiological mechanisms that have found linkage with obesity and breast, colon, lung, and prostate cancers. Furthermore, the article has also highlighted how these new insights into the processes occur and, due to which reasons, obesity contributes to tumorigenesis. This review provides a detailed discussion on the progression, which can assist in the development of new and innovative techniques to interfere in this process, and it has been supported with insights based on evidence literature on approved clinical treatments for obesity and cancer.

In 2019, the International Agency for Research on Cancer re-evaluated the carcinogenicity of night-shift work and reported that there is limited evidence that night-shift work is carcinogenic for the development of prostate cancer. Therefore, in 2020 and 2021, the Korean Epidemiologic Investigation Evaluation Committee concluded that 2 cases of prostate cancer were occupational diseases related to the night-shift work. Here, we report the 2 cases of prostate cancer in night-shift workers which were first concluded as occupational diseases by the Korean Epidemiologic Investigation Evaluation Committee.

Patient A: A 61-year-old man worked as a city bus driver for approximately 17 years, from 2002 to 2019, and was exposed to night-shift work during this period. In March 2017, the patient was diagnosed with high-grade prostate cancer through core-needle biopsy after experiencing stinging pain lasting for 2 months. Patient B: A 56-year-old man worked as an electrician and an automated equipment operator in a cement manufacturing plant for 35 years from 1976 to 2013 and was exposed to night-shift work during this period. In 2013, the patient was diagnosed with high-grade prostate cancer through core needle biopsy at a university hospital because of dysuria that lasted for 6 months.

The 2 workers were diagnosed with high-grade prostate cancer after working night shifts for 17 and 35 years respectively. Additionally, previous studies have reported that high-grade prostate cancer has a stronger relationship with night-shift work than low or medium-grade prostate cancer. Therefore, the Korean Epidemiologic Investigation Evaluation Committee concluded that night-shift work in these 2 patients contributed to the development of their prostate cancer.

Though obesity, measured by body mass index (BMI), is an established risk factor for several cancer sites, there is conflicting evidence on whether obesity increases prostate cancer risk or mortality and, if it does, whether it increases risk directly or indirectly by affecting prostate cancer screening efficacy.

We examined associations between BMI and prostate cancer screening outcomes, incidence, and mortality in men randomly assigned to the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (n = 36 756) between 1993 and 2001. Participants received annual screening with the prostate-specific antigen test and digital rectal exam. Associations between baseline BMI and screening outcomes were assessed via multinomial logistic regression, and associations with prostate cancer incidence and mortality were assessed via Cox proportional hazards regression.

Individuals with higher BMI were less likely to screen positive via the prostate-specific antigen test and/or digital rectal exam and more likely to have an inadequate screen (all Ptrend < .01). Higher BMI was inversely associated with prostate cancer incidence (per 5 kg/m2 BMI increase: hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.91 to 0.97), including incidence of early stage (HR = 0.94, 95% CI = 0.90 to 0.97) and advanced-stage (HR = 0.91, 95% CI = 0.82 to 1.02) disease, but positively associated with prostate cancer mortality (HR = 1.21, 95% CI = 1.06 to 1.37). The association with mortality was not modified by screening outcome (Pinteraction = .13).

Within this screened population, individuals with higher BMI had lower risk of prostate cancer diagnosis but higher risk of prostate cancer mortality. As higher BMI was not positively associated with advanced-stage prostate cancer risk, the increased mortality is unlikely to be due to delayed prostate cancer detection.

Metabolic and bariatric surgery (MBS) is the most effective intervention for weight loss leading to significant resolution of obesity-related medical conditions. Recent literature has demonstrated risk reduction of certain cancer types after MBS. Studies have shown an overall reduction in the risk of hormonal cancer, such as breast and endometrial cancer. However, the association between bariatric surgery and the incidence of various types of non-hormonal cancer such as esophageal, gastric, liver, gallbladder, colorectal, pancreatic and kidney cancer remains contested. The aim of this study was to highlight obesity and its relationship to cancer development as well as bariatric surgery and its role in cancer reduction with focus on non-hormonal cancers.

Obesity is a weight-related disorder characterized by excessive adipose tissue growth and dysfunction which leads to the onset of a systemic chronic low-grade inflammatory state. Likewise, inflammation is considered a classic cancer hallmark affecting several steps of carcinogenesis and tumor progression. In this regard, novel molecular complexes termed inflammasomes have been identified which are able to react to a wide spectrum of insults, impacting several metabolic-related disorders, but their contribution to cancer biology remains unclear. In this context, prostate cancer (PCa) has a markedly inflammatory component, and patients frequently are elderly individuals who exhibit weight-related disorders, being obesity the most prevalent condition. Therefore, inflammation, and specifically, inflammasome complexes, could be crucial players in the interplay between PCa and metabolic disorders. In this review, we will: 1) discuss the potential role of each inflammasome component (sensor, molecular adaptor, and targets) in PCa pathophysiology, placing special emphasis on IL-1β/NF-kB pathway and ROS and hypoxia influence; 2) explore the association between inflammasomes and obesity, and how these molecular complexes could act as the cornerstone between the obesity and PCa; and, 3) compile current clinical trials regarding inflammasome targeting, providing some insights about their potential use in the clinical practice.