Incidence Of Prostate Cancer Research Articles

Causal associations between socioeconomic status and prostate cancer using two-sample Mendelian randomization study

Prostate cancer (PCa) is a common form of malignancy among men. The associations between socioeconomic status (SES) indicators and PCa risks remain incompletely elucidated. Through two-sample Mendelian randomization (MR), this research seeks to assess the causal links between 4 genetically predicted SES indicators—average total household income before tax, the Townsend deprivation index at recruitment, unemployed status and college or university degree in the household—and PCa. Genetic variants were extracted from publicly available genome-wide association studies (GWAS) under stringent threshold as instrumental variables (IVs). We employed the inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger to estimate the causal effect, with sensitivity analyses such as Cochran’s Q tests, MR-Egger, MR-PRESSO and leave-one-out performed to detect potential heterogeneity and pleiotropy. Our MR analysis revealed a causal association between unemployment and prostate cancer (OR: 3.07, 95%CI:1.12–8.42, P = 0.03). No causal associations were identified between other SES components and prostate cancer. The MR-PRESSO suggested 2 outliers in the association between college or university degree in household and prostate cancer, which rendered the association significant after outliers were removed. The heterogeneity and pleiotropy are unlikely to affect our causal estimate. Our results indicated that unemployment poses a potential risk factor for the incidence of PCa. The findings highlight the necessity for further exploration into the underlying etiology of PCa.

Computer-aided diagnosis based on 3D deep convolutional neural network system using novel 3D magnetic resonance imaging sequences for high-grade prostate cancer

Abstract Background With the rising incidence of prostate cancer (PCa), there is a global demand for assistive tools that aid in the diagnosis of high-grade PCa. This study aimed to develop a diagnostic support system for high-grade PCa using innovative magnetic resonance imaging (MRI) sequences in conjunction with artificial intelligence (AI). Materials and methods We examined image sequences of 254 patients with PCa obtained from diffusion-weighted and T2-weighted imaging, using novel MRI sequences before prostatectomy, to elucidate the characteristics of the 3-dimensional (3D) image sequences. The presence of PCa was determined based on the final diagnosis derived from pathological results after prostatectomy. A 3D deep convolutional neural network (3DCNN) was used as the AI for image recognition. Data augmentation was conducted to enhance the image dataset. High-grade PCa was defined as Gleason grade group 4 or higher. Results We developed a learning system using a 3DCNN as a diagnostic support system for high-grade PCa. The sensitivity and area under the curve values were 85% and 0.82, respectively. Conclusions The 3DCNN-based AI diagnostic support system, developed in this study using innovative 3D multiparametric MRI sequences, has the potential to assist in identifying patients at a higher risk of pretreatment of high-grade PCa.

Neighborhood socioeconomic disparities in cancer incidence following a hypothetical intervention to increase residential greenspace cover in the UK Biobank cohort

BackgroundHigher greenspace exposure has been associated with lower risk of certain cancers. However, few studies evaluated potential benefits of increasing population-level exposure to greenspace on cancer disparities. We estimated the impact of a hypothetical intervention to increase residential greenspace cover on neighborhood socioeconomic disparities in total, breast, colorectal, lung, and prostate cancer incidence. MethodsOur study included 411,787 cancer-free UK Biobank participants. Percentage of greenspace around baseline residential addresses (300m, 1000m distance buffers) was derived by combining domestic gardens and greenspace cover from the Generalised Land Use Database. We categorized neighborhood socioeconomic deprivation using the Index of Multiple Deprivation 2010. We estimated hazard ratios (HR) and 95% confidence intervals (CI) of each cancer associated with greenspace, adjusting for sociodemographic and lifestyle factors. We additionally adjusted for air pollution in supplementary analyses as we a-priori hypothesized that it was on the causal pathway between greenspace and cancer. Further, we used parametric g-computation to calculate the standardized 10-year risk of each cancer, comparing the least to most socioeconomically disadvantaged participants, both without any hypothetical greenspace intervention and under a hypothetical intervention to increase residential greenspace cover to a favorable threshold (75th percentile amongst the least socioeconomically deprived participants). ResultsWe documented 40,519 incident cases of cancer over 4,210,008 person-years follow-up. An interquartile range increase in greenspace cover within 300m was associated with lower incidence of total (HR 0.98; 95% CI 0.97, 1.00) and lung (HR 0.96; 95% CI 0.92, 0.99) cancer, and was suggestively associated with lower prostate and breast cancer incidence, but not colorectal cancer. Additional adjustment for fine particulate matter air pollution (PM2.5) weakened lung cancer associations but strengthened breast and prostate cancer associations (e.g., 300m prostate cancer HR 0.93; 95% CI 0.89, 0.97). The hypothetical intervention to increase greenspace (300m) resulted in 1.3 fewer total cancer cases per 1000 (95% CI 1.0, 1.6) in the most compared to least deprived group, a 23% reduction in the socioeconomic disparity gap. DiscussionHigher residential greenspace cover was associated with lower total, breast, lung, and prostate cancer incidence. Policies to increase residential greenspace cover may reduce the risk of certain cancers, particularly among socioeconomically disadvantaged groups.

Sociodemographic landscape of suspected prostate cancer referrals and diagnoses across North East London.

The objective of this study is to identify healthcare inequities in referrals and diagnoses of suspected prostate cancer (PCa) in an ethnically diverse and socially deprived large urban region. Retrospective cohort study of 2-Week Wait (2WW) suspected PCa patients (n= 12 947) referred to two acute NHS Trusts in North East London (NEL) from February 2019 to August 2023. Sociodemographics, diagnosis and pretreatment staging data were collected from patient records. We examined referral and diagnosis statistics, age at referral, radiological T-stage at diagnosis, levels of deprivation by ethnicity and the impact of COVID-19 pandemic lockdowns on proportion of referrals and diagnoses by ethnicity and T-stage at diagnosis. Uni- and multivariable logistic regression was performed to identify predictors of locally advanced (T-stage ≥T3) disease. Of all referrals, 22% were diagnosed with PCa. There were no statistically significant differences in referrals, diagnoses or T-stage of PCa by ethnicity during COVID lockdown versus non-lockdown periods (p> 0.05). Compared to men from any other ethnicity, Black men (from Black British, Black African and Black Caribbean ethnic groups) were diagnosed at a younger age (mean = 65 years), had the highest age-adjusted PCa incidence rate of 149 per 100 000 person-years, were from the most deprived backgrounds, and were diagnosed with the highest proportion of localised PCa (74%). Multivariable analysis of a patient subgroup revealed age bands 71-80 years (OR 2.01, 95% CI 1.31-3.07) and >80 (OR 4.27, 95% CI 2.25-8.08) as independent positive predictors of locally advanced PCa, and Black ethnicity as an independent predictor of localised disease (OR 0.66, 95% CI 0.43-1.00). Limitations of this study include the exclusion of PCa cases diagnosed outside the 2WW pathway, as well as missing data on Prostate-Specific Antigen (PSA) levels, distant radiological staging and histopathological findings. We identify disparities in PCa incidence, stage and age at presentation, as well as socio-economic deprivation among Black men in NEL. Targeted efforts are needed to mitigate these healthcare inequities.

Development and validation of a predictive score for diagnosing prostate cancer in primary care.

Prostate cancer (PCa) represents the fifth cause of death in the male population worldwide. The prostate-specific antigen (PSA) test demonstrated poor accuracy to assess the presence of PCa. Thus, the PSA testing paradigm should be moved from the systematic screening approach to the early identification of men who are harbouring clinically significant disease. Accurate clinical-based tools to predict PCa should therefore be developed for general practice. We derived and validated a PCa predictive score using a primary care data source. Using the Italian Health Search Database, we formed a cohort of men aged 45-90 years in the period between 2002 and 2015. These patients were followed up until 31 December 2022. Those with less than a 5-year follow-up were excluded. The cohort was randomly divided into 'derivation' and 'validation' samples in a 1:1 ratio. Along with the demographic and clinical determinants forming the score, we investigated the role of PSA kinetics in the prediction accuracy. In a cohort of 529,082 men aged 45+ years, we identified 14,524 cases of PCa (incidence rate = 2.71 per 1000 person-years; 95% confidence interval = 2.67-2.80). The prediction accuracy of the PCa-HScore featured an explained variation of 12% and a discrimination power of 70%. The calibration slope was almost equal to 1 (p = 0.951, tested for equivalence against the 'perfect' slope) and the PSA kinetics did not improve the prediction accuracy. The PCa-HScore might guide the prescription of PSA and/or other clinical strategies in those men reporting certain levels of risk. A related decision support system could therefore be implemented in primary care.

Antibody‑drug conjugates in prostate cancer: Emerging strategies to enhance therapeutic index and current clinical landscape (Review).

The global incidence of prostate cancer (PCa) is rising. Localized PCa can be managed through surgical intervention or radiotherapy, but certain patients may experience recurrence or develop metastatic disease following localized treatment. Despite aggressive therapeutic approaches, the majority of metastatic patients with PCa will eventually progress to metastatic castration‑resistant PCa, with limited treatment alternatives and a dismal prognosis. The treatment options for advanced PCa are continuously evolving, yet there remains a demand for further innovative therapeutic approaches. Antibody‑drug conjugates (ADCs) represent a novel class of targeted medications comprising a humanized monoclonal antibody, a linker and a cytotoxic payload. ADCs primarily bind to antigens that are upregulated on the surface of PCa cells but are minimally expressed on normal cells. At present, a variety of targets for ADCs have been identified in the treatment of PCa, encompassing prostate‑specific membrane antigen, STEAP family member 1, trophoblast cell‑surface antigen 2, CD46, B7‑H3, tissue factor and delta‑like protein 3, each with one or more specific ADC that has shown encouraging results in the PCa field. In the present review, the developmental course, composition and mechanism of action of ADCs are explored, with a specific focus on recently published studies and ongoing trials aimed at investigating the efficacy and safety of ADCs in treating PCa. Lastly, ongoing challenges in ADC development and corresponding strategies to combat them are discussed.

Long-term exposure to ambient air pollutants and risk of prostate cancer: a prospective cohort study.

Air pollution has been hypothesized as a potential risk factor for prostate cancer, while previous studies on the topic mainly focused on single pollutant and the results were inconsistent. This study aimed to investigate the association between long-term exposure to multiple air pollutants and the risk of prostate cancer and their joint effect. This study included 210,722 men free of prostate cancer at baseline from the UK Biobank. Data on ambient air pollutants, including particulate matter with diameters ≤2.5 μm (PM2.5), ≤10 μm (PM10), nitrogen oxides (NO2 and NOx), sulfur dioxide (SO2), benzene, and ozone (O3) were collected from the UKs Department for Environment, Food and Rural Affair during 2003-2021. During a median follow-up of 10.9 years, a total of 10,841 incident prostate cancer occurred. The hazard ratios (95% confidence intervals) of prostate cancer for each interquartile range increase in PM2.5, PM10, NO2, NOx, SO2, benzene and O3 were 1.120 (1.084-1.158), 1.121 (1.089-1.155), 1.040 (1.009-1.071), 1.040 (1.012-1.069), 0.983 (0.958-1.009), 1.080 (1.050-1.111), and 1.080 (1.050-1.111), respectively. The joint effect of PM2.5, PM10, NO2, NOx, benzene, and SO2 was 1.039 (1.012-1.067). with the greatest contribution from NOx, PM10, benzene, and PM2.5. The impact of PM2.5, PM10, NO2, NOx and benzene on prostate cancer risk was weakened by a higher percentage of greenness at the home location buffer. Long-term exposure to air pollutants may be positively associated with an elevated risk of prostate cancer, particularly for NOx, PM10, benzene, and PM2.5. This study highlights the potential role of comprehensively assessing and controlling various air pollutants in prevention of prostate cancer.

Comparing PSA Screening Patterns and Their Role as Predictor of Prostate Cancer Diagnosis: Analysis of a Contemporary North American Cohort.

PSA screening remains a pivotal tool for early prostate cancer (PCa) detection. International guidelines rely on evidence from three major randomized clinical trials: ERSPC, PLCO, and CAP. We aim to examine the percentage of patients in real-world practice who get PSA screening as defined by each of the aforementioned trials. Moreover, we seek to evaluate if the different PSA screening patterns have a different impact on PCa incidence and its features at diagnosis. Our institutional database was queried to identify men aged 55-69 who received at least one PSA test, did not develop PCa or die within 6 years of the initial test, had follow-up within our system at least 6 years after the initial test, and did not have a previous PCa diagnosis. A total of 28,612 patients met our selection criteria. We categorized patients into three distinct PSA screening patterns based on testing frequency (PLCO: 1 PSA test per year for 6 years; ERSPC: 2 or 3 PSA tests over 6 years; CAP: 1 PSA test over 6 years). Our primary outcomes were any PCa incidence and clinically significant PCa (csPCa, defined as ISUP ≥ 3) incidence. Secondary outcome was the rate of cM1 disease. Competing risks cumulative incidence curves were used to depict any PCa and csPCa diagnosis with death before a diagnosis considered a competing risk. Multivariable competing risks regression (CRR) was used to assess the impact of the different screening patterns on any PCa and csPCa incidence, after adjusting for confounding factors. The most prevalent PSA screening pattern was ERSPC, including 15,530 patients (54.3%), followed by the CAP with 9003 patients (31.5%), and the PLCO with only 4079 patients (14.2%). The median (IQR) follow-up time was 4.8 (1.7-10.8) years. At 10 years, any PCa incidence was 7.4% versus 5.6% versus 2.5% for PLCO versus ERSPC versus CAP, respectively, while for csPCa, the rates were 2.5% versus 2.5% versus 1.2% (both p < 0.001). On multivariable analyses, PLCO and ERSPC patterns were associated with 2.92-fold and 2.31-fold higher risks from 1 year to the next of any PCa diagnosis, respectively, compared to CAP pattern (both p < 0.001). Similarly, patients with PLCO and ERSPC patterns had 2.07-fold and 2.31-fold higher risks, respectively, of csPCa diagnosis compared to CAP pattern (both p < 0.001). In men with PCa diagnosis, the rates of cM1 disease were respectively 1.7% vs 5.6% vs 10.8% for PLCO versus ERSPC versus CAP, respectively (p = 0.0009). We observed that the most common screening pattern in "real-world" clinical practice is close to what ERSPC recommend, and this pattern seems to achieve a reasonable reduction in the risk of advanced PCa, while limiting overdiagnosis.

Trends in Prostate Cancer Incidence and Mortality Rates

Incidence of distant stage prostate cancer is increasing in the United States. Research is needed to understand trends by social and geographic factors. To examine trends in prostate cancer incidence and mortality rates in California by stage, age, race and ethnicity, and region. This cohort study used mortality data from the California Cancer Registry and California Department of Public Health's Center for Health Statistics, and incidence data from the National Cancer Institute Surveillance, Epidemiology, and End Results program and the US Census. The dataset for these analyses was released in April 2024. Participants included males residing in California between 2004 and 2021. Analyses were conducted from April to October 2024. Stage at diagnosis, age, race and ethnicity, and region of California. The delay-adjusted incidence rates and mortality rates were calculated and age-adjusted to the 2000 US standard population. Annual percentage changes (APC) were calculated using NCI's Joinpoint Regression Program. Between 2004 and 2021, there were 387 636 prostate cancer cases (27 938 distant stage) and 58 754 prostate cancer deaths in California. In this study, 203 038 cases (52.4%) occurred among males aged 55 to 69 years, and 153 884 (39.7%) occurred among males 70 years or older. The distribution of race and ethnicity among cases was: 1031 American Indian or Alaska Native (0.3%); 31 366 Asian American, Native Hawaiian, and Pacific Islander (8.1%); 66 695 Hispanic or Latino (17.2%); 36 808 non-Hispanic Black (9.5%); 238 229 non-Hispanic White (61.5%); and 13 507 unknown or other races (3.5%). On average, the incidence of distant prostate cancer increased 6.7% (95% CI, 6.2% to 7.3%) per year between 2011 and 2021. By race and ethnicity, the APC ranged from 6.5% (95% CI, 4.2% to 13.4%) among Asian American, Native Hawaiian, and Pacific Islander males between 2011 and 2021 to 8.0% (95% CI, 6.9% to 9.5%) among Hispanic males between 2014 and 2021. In 9 of the 10 California regions, the incidence of distant prostate cancer increased by approximately 6% or more per year. Prostate cancer mortality rates declined 2.6% per year between 2004 and 2012 but plateaued between 2012 to 2021 (APC, 0.1%; 95% CI, -0.6% to 1.6%). The plateau in mortality occurred across ages, races and ethnicities, and regions. In this cohort study among California residents, the incidence of distant stage prostate cancer increased throughout the state between 2011 and 2021. Mortality rates plateaued between 2012 and 2021, ending previous decades of decline. Implementation of more effective prostate cancer screening strategies are critically needed.

Hypofractionated image-guided radiotherapy with 70 Gy in 28 fractions for prostate cancer confined to the pelvis: a single institute experience in Taiwan

BackgroundThe incidence of prostate cancer is increasing in Asian countries. Although moderately hypofractionated radiotherapy is not inferior to conventional fractionated radiation according to the updated guidelines, data regarding its efficacy and safety in Taiwan are currently lacking. The aim of this study was to investigate the outcomes of prostate cancer patients treated with hypofractionated image-guided radiotherapy at a single institution in Taiwan.MethodsWe retrospectively included patients with prostate cancer across all risk groups who were treated with hypofractionated image-guided radiotherapy 70 Gy (Gy) in 28 fractions (at 2.5 Gy/fraction) between 2007 and 2022. We analyzed treatment efficacy by assessing overall survival, prostate cancer-specific survival, event-free survival, biochemical failure, locoregional recurrence, and distant metastasis. The safety of the treatment was evaluated through acute and late gastrointestinal (GI) and genitourinary (GU) toxicity grading based on the Radiation Therapy Oncology Group criteria. Event-free survival, overall survival, prostate cancer-specific survival, biochemical failure, locoregional recurrence, and distant metastasis were evaluated using the Kaplan–Meier method.ResultsWe identified 150 consecutive men with prostate cancer: 12.7% were at low risk, 32.7% were at intermediate risk, 44.6% were at high risk, and 10% had N1 disease. The median follow-up time was 68.9 months (range: 2.3–172 months). The 5-year overall survival rate was 91.7% for the entire cohort, with rates of 100%, 94.3%, 93.3% and 71.1% for the low-risk, intermediate-risk, high-risk, and N1-disease groups, respectively (p < 0.001). The 5-year event-free survival rate for all patients was 75.8%. Among the risk groups, the 5-year event-free survival rates were 100%, 86.3%, 68.3% and 52.5% for the low-risk, intermediate-risk, high-risk, and N1 disease groups, respectively (p < 0.001). Grade ≥ 2 late GI toxicity was rare (0.7%), and grade ≥ 2 late GU toxicity was observed in 9.3% of the patients.ConclusionsHypofractionated image-guided radiotherapy, delivering 70 Gy at 2.5 Gy per fraction, is both effective and safe for Taiwanese patients with prostate cancer across all risk groups, consistent with findings from existing large randomized trials. Therefore, as a solution to enhance patient convenience, hypofractionated radiotherapy is a reasonable option for the definitive treatment of prostate cancer.Trial registrationNot applicable.

Comparative Analysis of the Incidence, Diagnosis and Treatment of Prostate Cancer between China and the United States

In the context of globalization and an aging population, prostate cancer has emerged as a significant threat to male health, with its incidence and mortality rates on the rise worldwide. Particularly in comparison between China and the United States, two representative countries, there are notable differences in the incidence, diagnosis, and treatment of prostate cancer due to variations in medical resource allocation, diagnostic techniques, lifestyles, and cultural perceptions. This article aims to compare and analyze the current status of prostate cancer in China and the U.S., explore the key factors influencing these differences, and provide references for the development of prostate cancer prevention and control strategies in China. We employ multi-dimensional data collection and analysis approaches including literature review, case-control studies, and statistical analysis. We focus on the epidemiological data, clinical practice guidelines, patient quality of life, and medical economic burden to comprehensively dissect the differences and their causes in prostate cancer management between China and the U.S. Our findings highlight the disparities between the two countries in the aspects of early screening, treatment preference, and long-term follow-up mechanisms, aiming to uncover the underlying reasons behind these differences and propose corresponding improvement suggestions. Conclusions drawn from our analyses indicate that the U.S. is relatively advanced in early diagnosis and personalized treatment of prostate cancer, benefiting from a more comprehensive healthcare system and advanced medical technologies. Although China has made a significant progress in recent years, it still faces many challenges due to the uneven distribution of medical resources, and there is space for improvement in public health awareness. The significance of our analysis lies in providing empirical evidence for formulating more scientifically sound and reasonable strategies for the prevention and control of prostate cancer in China, which will help promote further development and improvement in this field.

Prostate-specific antigen screening at low thresholds of men with pathogenic BRCA1/2 variants.

Men with pathogenic BRCA1/2 variants are at higher risk of prostate cancer We included men with likely pathogenic/pathogenic (LP/P) variants in BRCA1/2 in a prostate-specific antigen (PSA) screening program after cascade germline testing since 2014. PSA was tested yearly and an age-specific low PSA threshold for biopsy was used, to determine if a low PSA threshold for biopsy is justified for men with pathogenic BRCA1/2 variants. From 2014 to 2023 a total of 340 men were included in the program. We report demographics, clinical characteristics, and treatment outcomes at 7 years. The cumulative incidence of a primary biopsy was 37% (95CI: 31‒43) after 7 years. Incidence of prostate cancer diagnosis was 11% (95CI: 7.1‒15). Men referred were 7.8 (95CI: 5.3‒11, p < 0.001) times more likely to be diagnosed with prostate cancer than the general Danish male population. The cumulative incidence of biochemical failure (PSA > = 0.2 ng/ml) 4 years after RP was 22% (95CI: 2.3‒41). The main limitation is that not all men underwent a pre-biopsy MRI. We found a high incidence of prostate cancer in men with LP/P BRCA1/2 variants, but this may be explained by the low PSA threshold for scheduling biopsies. More studies are needed to compare this patient population to men with other germline features. The high risk of recurrence after curative therapy is worrisome and requires further evaluation as to whether this is a biological phenomenon.

Understanding the role of metabolic syndrome in prostate cancer risk: A UK Biobank prospective cohort study

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 double disparity: Vitamin D deficiency and lethal prostate cancer in black men.

Epidemiological data from as early as the 1930s documented a dramatic racial disparity in prostate cancer incidence, survival, and mortality rates among Black men-a trend that persists to this day. Black men are disproportionately burdened by prostate cancer, developing the disease at younger ages, facing more aggressive and lethal forms, and ultimately experiencing double the mortality rate of men of European descent. Investigating the multifactorial contributors to this racial disparity has been extensive, but results have often been inconsistent or inconclusive, making it difficult to pinpoint clear correlations. However, there is strong evidence suggesting that vitamin D deficiency is significantly associated with lethal forms of prostate cancer. This is particularly important given that Black men are at a higher risk for both vitamin D deficiency and developing aggressive, lethal prostate cancer, presenting a double disparity. The disparity in prostate cancer and vitamin D extends to Black men outside the US, but most of the studies have been done in African American men. Understanding the available evidence on vitamin D deficiency and its influence on prostate cancer biology may reveal new opportunities for prevention and therapeutic intervention.

Vitamin D-related genetic variants and prostate cancer risk in Black men.

The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men. We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide association study data for approximately 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men for comparison. A statistical significance threshold of 0.000685 was used to account for the 73 variants tested. None of the variants examined were significantly associated with prostate cancer risk among Black men after multiple comparison adjustment. Suggestive associations (P < 0.05) for four variants were found in Black men, including two in RXRA (rs41400444 OR=1.09, 95 % CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with risk in White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055). We observed suggestive associations between genetic variants in RXRA and VDR and prostate cancer risk in Black men. Future research exploring the relationship of vitamin D with cancer risk in Black men will need larger sample sizes to identify ancestry-specific variants relevant to risk in this population.

UBE2S, downregulated by miR-152-3p, facilitates prostate cancer progression through the PTEN-mediated AKT/mTOR pathway.

In recent years, the incidence and mortality rates of prostate cancer (PCa) have still not been significantly reduced and the mechanisms of tumor onset and progression are still not fully understood. The pathogenic mechanisms and upstream regulation of UBE2S expression in prostate cancer have not been elucidated. Here, we performed bioinformatic analysis of public databases to reveal the expression of UBE2S in PCa and its association with Gleason score, tumor staging, biochemical recurrence, and survival. Subsequently, the effect of UBE2S on the proliferation and invasive capacity of PCa cells was explored. Next, miR-152-3p was identified to bind to the 3'-UTR of UBE2S mRNA and down-regulated in PCa through luciferase reporter assays. Dual immunofluorescence assay and co-immunoprecipitation assays were performed to verify the regulatory role of UBE2S on PTEN. Finally, the molecular mechanism of UBE2S regulation of PCa progression was further confirmed by rescue experiments and in vivo nude mouse subcutaneous transplantation tumor experiments. UBE2S expression was upregulated in PCa and correlated with patient Gleason score, TNM stage, biochemical recurrence, and disease-free survival. miR-152-3p regulated UBE2S expression in PCa by binding to the UBE2S mRNA 3'-UTR. Mechanistically, UBE2S combines with PTEN and ubiquitinates it, leading to PTEN degradation and ultimately promoting PCa progression via the AKT/mTOR signaling pathway. UBE2S, down-regulated by miR-152-3p, plays an important role in the onset and progression of PCa through the PTEN-mediated Akt/mTOR pathway and may become a new diagnostic marker and therapeutic target for PCa.

Rethinking prostate cancer screening in transgender women

Introduction: Over the years, the number of people openly identifying as transgender has steadily increased, leading to a greater need for transgender-specific healthcare information. Among transgender women (TW), there remains a risk of prostate cancer since the prostate is not removed during gender-affirming hormone therapy (GAHT) or surgery; however, there is limited knowledge about prostate cancer screening in the transgender population. Although there are few reported cases of prostate cancer screening or prostate-specific antigen (PSA) testing in TW, the impact of hormone therapies on PSA levels is well-documented. Notably, GAHT for TW and hormone therapy for treating prostate cancer share similarities. Drawing on these similarities, we aimed to develop guidelines for baseline PSA levels and prostate cancer screening in TW. Methods: Through a systematic review, we examined the existing PubMed publications on PSA levels and prostate cancer screening in TW, as well as expected PSA levels in patients with prostate cancer undergoing hormone therapies. We also investigated other aspects considered for the diagnosis of prostate cancer. Given the limited research on TW, we also included relevant case studies. These publications and case reports were reviewed and analyzed to create a comprehensive overview of expected baseline PSA levels and prostate cancer screening guidelines for TW. Results: Currently, there are no established guidelines for PSA or prostate cancer screening in TW; however, these case studies indicated a range of PSA values from 3.3 to &lt;100 ng/ml. Existing literature on expected PSA levels in prostate cancer patients undergoing hormone therapy shows a reduction in PSA of over 50% post-therapy. This evidence suggests that PSA values in TW presenting with prostate cancer may be lower than those observed in cisgender males with the disease. Conclusions: While TW exhibit lower prostate cancer incidence compared to cisgender men, the impact of hormone therapy on PSA levels presents significant challenges for screening and diagnosis. The parallels between PSA level reductions in TG women and cisgender men undergoing estrogen therapy highlight the need for revised screening protocols. Addressing these challenges through targeted research and personalized care approaches will be vital for improving prostate cancer management in transgender individuals.

Incidence, trends and patterns of female breast, cervical, colorectal and prostate cancers in Antigua and Barbuda, 2017–2021: a retrospective study

BackgroundGlobally, estimates of cancer cases and deaths have increased since 2018, particularly in Latin America and Caribbean countries. In Antigua and Barbuda, understanding the burden of common cancers such as female breast, cervical, colorectal and prostate cancers is critical. This study aimed to assess the incidence, trends, and patterns of these four cancers from 2017 to 2021.MethodsUsing a retrospective observational study design, information on these cancers was abstracted from medical records at four key study sites in Antigua and Barbuda. Estimates of age-specific and age-standardized incidence were determined using direct standardization. The KeyFitz method was used to derive standard errors and confidence intervals. Derived estimates were employed to analyze trends and Joinpoint regression modeling was used to determine annual percentage change.ResultsBetween 2017 and 2021, 391 cases of female breast (41.7%), cervical (10.2%), colorectal (20.2%) and prostate (27.9%) cancers were diagnosed. Overall mean age at presentation was 61.5 (± 12.9) years, ranging from 24 to 94 years, age-standardized incidence rate 65.2 (95% CI: 58.7–71.6) per 100,000 population. Age-standardized incidence rate for female breast cancer was 49.9 (95% CI: 42.2–57.8), annual percentage change in incidence a low of -0.2%. Prostate cancer had the second highest age-standardized incidence rate at 41.6 (95% CI: 33.8–49.4), annual percentage change showed a gradual but steady increase at 21.7%. Per cancer types, variations in age-standardized incidence rates were noted across age-groups, year-of-presentation, and parishes. Collectively, there was an 8.1% (95% CI: -14.9–37.6) annual percentage change increase in age-standardized incidence rates between 2017 and 2021. Incident cases, age-standardized incidence rates, and trends per cancer type are expected to gradually increase during 2022–2030 (average annual percentage increase is 3.4%).ConclusionsThis study is a first step in providing reasonable evidence on the incidence, trends, and patterns of four common cancers in Antigua and Barbuda. Female breast and prostate cancers were the dominant cancer types in terms of incidence, age-standardized incidence and predicted increasing incidence trends. Variableness in cancer-specific age-standardized rates across parishes and years of presentation were observed. Besides research, this study has importance for instituting cancer prevention and control measures, including surveillance and healthy lifestyles initiatives.

The burden of prostate cancer in the North Africa and Middle East Region from 1990 to 2021

Prostate cancer ranks among the most prevalent malignancies affecting males globally. This study sought to document the incidence, deaths and disability-adjusted life-years (DALYs) that were due to prostate cancer in the Middle East and North Africa (MENA) region, and its 21 countries, from 1990 to 2021. We analysed publicly accessible data from the Global Burden of Disease 2021 study to present findings on the incidence, deaths, and disability-adjusted life years (DALYs) associated with prostate cancer. These metrics were reported as counts and age-standardised rates, each accompanied by 95% uncertainty intervals. In 2021, the age-standardised incidence of prostate cancer in the region was 27.4 per 100,000 population, representing a 125.1% increase from 1990. The age-standardised mortality rate was 10.1, and the age-standardised DALY rate was 173.6, neither of which showed significant increases since 1990. Qatar recorded the highest age-standardised DALY rate in 2021, while Algeria had the lowest. The largest number of incident cases, deaths, and DALYs in 2021 were found in the 65–69, 80–84, and 70–74 age groups, respectively. Additionally, from 1990 to 2021, the burden of prostate cancer largely increased with the socio-demographic index (SDI) at the regional level. The burden of prostate cancer in the MENA region rose markedly between 1990 and 2021. Further studies into the underlying causes of this increasing incidence are essential to devise effective strategies for the early detection and prevention of the disease.

Small Area Estimation of PSA Testing in US States and Counties.

In 2012, the US Preventive Services Task Force recommended against prostate cancer screening using the PSA test for all age groups. In 2018, the US Preventive Services Task Force's recommendation shifted from a "D" (not recommended) to a "C" (selectively offering PSA-based screening based on professional judgment and patient preferences) in men ages 55 to 69. Limited reliable county-level prostate cancer screening data are available for cancer surveillance purposes. Utilizing data from the National Health Interview Survey (NHIS) and Behavioral Risk Factor Surveillance System (BRFSS) collected in 2012 to 2019, state- and county-level small area models were developed for estimating PSA testing. Model diagnosis, internal validation, and external validation examining associations of PSA testing and prostate cancer incidence were conducted. Model-based estimates of PSA testing rates were produced for all US states and 3,142 counties for two data periods: 2012 to 2016 and 2018 to 2019. Geographic variations across counties were demonstrated through maps. Moderate positive correlations between PSA-based screening and prostate cancer incidence were observed, e.g., the state-level weighted Pearson's correlation coefficients were 0.5025 (P value = 0.0002) and 0.3691 (P value = 0.0077) for 2012 to 2016 and 2018 to 2019, respectively. These modeled estimates showed improved precision and adjusted for the differences between the BRFSS and NHIS. The approach of combining the NHIS and BRFSS utilized strengths of the larger sample size of the BRFSS and generally higher response rates and better household coverage from the NHIS. The resulting small area estimates offer a valuable resource for the cancer surveillance community, aiding in targeted interventions, decision making, and further research endeavors.