Etiology Of Prostate Cancer Research Articles

Ambient air pollution and prostate cancer in a population-based Canadian case-control study

BACKGROUND AND AIM: Age, ethnicity and family history are the only established risk factors for prostate cancer, but they are not modifiable. Other risk factors have been investigated, with inconsistent findings. A possible role of air pollution, which has been classified as a human carcinogen, has been suggested yet there have been few studies of prostate cancer. METHODS: We conducted a case-control study in eight Canadian provinces to investigate the relationship between PM2.5 and NO2 and incident prostate cancer. Participants provided data between 1994 and 1997 and the development of air pollution historical surfaces now permits risks to be estimated. 1416 cases of prostate cancer and 1426 controls who reported addresses between 1975 and 1994 were examined. Three methods were used to measure the mean exposure to PM2.5 and NO2: (1) satellite-derived observations; (2) satellite-derived observations scaled with historical fixed-site measurements of PM2.5 and NO2; and (3) a national land-use regression (LUR) model for NO2. Odds ratios (OR) and 95% confidence intervals (CI) were estimated per interquartile range (IQR) increase in PM2.5 and NO2 using logistic regression. RESULTS:We found a positive association between prostate cancer and both measures of PM2.5 from 1975 to 1994; for an increase of 1 IQR of PM2.5, the OR adjusted for personal and contextual factors was 1.27 (95% CI: 1.09-1.54) while for the satellite derived-observation the OR was 1.21 (95% CI: 1.04-1.41). We also observed positive associations for NO2. The ORs for satellite-derived observations and scaled satellite-derived observations of NO2, adjusted for personal and contextual factors, were 1.05 (95% CI: 0.93-1.19) and 1.15 (95% CI: 0.97-1.36) per IQR increase, respectively. CONCLUSIONS:Our study highlights a potential role of air pollution in prostate cancer etiology. Given the paucity of studies on this topic, further research is needed exploring the role of screening and variations in risk by prostate cancer aggressiveness. KEYWORDS: prostate cancer, air pollution, PM2.5, NO2, case control study, Canada

A study on screening of knowledge attitude and practices regarding prostate cancer among men in Bangalore

Background: Prostate cancer is the most commonly diagnosed cancer among men .and the second most common cause of death from cancer in men worldwide. Aim and Objectives: The aim of the study was screening of knowledge attitude and practice regarding prostate cancer among men in Bangalore. Materials and Methods: It is A Hospital-based, Prospective, cross-sectional and observational study. Results: The study reveals that age group < 50> Conclusion: This study concludes the need for providing awareness regarding etiology of prostate cancer and highlights misconceptions regarding etiology of prostate cancer. The study recommends well-designed health education programs, widespread public health campaigns using the mass media, hospitals and religious centres. Leading to early detection and cure. Thereby reducing the morbidity and mortality rates. Keywords: Prospective, Cross-sectional, Prostate cancer.

Prevalence of Human Polyomavirus BK Virus in Prostate Cancer Patients and Benign Prostatic Hyperplasia: A Cross-sectional Study on Prostate Patients Referred to Imam Khomeini Hospital in Ahvaz Between 2015 and 2017

Background: Human polyomavirus BK virus (BKV) belongs to the Polyomaviridae family and seems to be a drastic virus in prostate cancer (PCa) etiology. BK virus induces oncogenesis via the expression of large tumor antigen (LTAg) and small tumor antigen (stAg). Also, BKV infection seems to play an essential role in prostate cancer development. Objectives: In this study was aimed to study the prevalence of BKV in benign and cancerous prostate tissues. Methods: In this study, 100 formalin-fixed paraffin-embedded tissues of PCa specimens and benign prostatic hyperplasia (BPH) were collected. The DNA was extracted from tissue samples, and the BKV DNA was investigated using a semi-nested polymerase chain reaction (PCR). The MEGA 6.0 software was used for phylogenetic analysis to assemble the viral genome. A phylogenetic tree was constructed by neighbor-joining analysis with 1,000 replicates of the bootstrap resampling test. Results: The BKV DNA was found in 66% (33/50) of patients with PCa and 36% (18/50) of patients with benign prostatic hyperplasia (BPH) (P = 0.003). The frequency of BKV DNA in different classes of Gleason score (5 - 10) was not significant (0.094). The distribution of BKV DNA among different age groups was not significant (P = 0.086). Conclusions: High frequency of BKV infection was detected in patients with PCa compared to patients with BPH (P = 0.003), and the coexistence of BKV DNA was confirmed in 51% (51/100) of tissue samples, which were confirmed to be subtype 1 of BKV infection.

Novel Prostate Cancer Biomarkers: Aetiology, Clinical Performance and Sensing Applications

The review initially provides a short introduction to prostate cancer (PCa) incidence, mortality, and diagnostics. Next, the need for novel biomarkers for PCa diagnostics is briefly discussed. The core of the review provides details about PCa aetiology, alternative biomarkers available for PCa diagnostics besides prostate specific antigen and their biosensing. In particular, low molecular mass biomolecules (ions and metabolites) and high molecular mass biomolecules (proteins, RNA, DNA, glycoproteins, enzymes) are discussed, along with clinical performance parameters.

Limitations of Explainability for Established Prognostic Biomarkers of Prostate Cancer.

High-throughput technologies do not only provide novel means for basic biological research but also for clinical applications in hospitals. For instance, the usage of gene expression profiles as prognostic biomarkers for predicting cancer progression has found widespread interest. Aside from predicting the progression of patients, it is generally believed that such prognostic biomarkers also provide valuable information about disease mechanisms and the underlying molecular processes that are causal for a disorder. However, the latter assumption has been challenged. In this paper, we study this problem for prostate cancer. Specifically, we investigate a large number of previously published prognostic signatures of prostate cancer based on gene expression profiles and show that none of these can provide unique information about the underlying disease etiology of prostate cancer. Hence, our analysis reveals that none of the studied signatures has a sensible biological meaning. Overall, this shows that all studied prognostic signatures are merely black-box models allowing sensible predictions of prostate cancer outcome but are not capable of providing causal explanations to enhance the understanding of prostate cancer.

Abstract 782: Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity

Abstract Introduction: Prostate cancer is the most common cancer in men and there is racial disparity in prostate cancer incidence and mortality globally, with greater disease burden in men of African ancestry, followed by European ancestry and least in men of Asian ancestry. The etiology of prostate cancer is not fully understood, but includes genetic and environmental factors. Present day non-Africans are reported to have introgressed DNA from Neanderthal and Denisovan ancestors. Over 170 prostate cancer associated single nucleotide polymorphisms (SNPs) have been identified from several genome-wide association studies (GWAS), with SNPS on chromosomes 2, 8 and 22 reported as showing variation between African and non-African men with prostate cancer. We performed analysis of prostate cancer associated SNPs on chromosomes 2, 8 and 22 to determine if DNA introgression could explain the racial variation. Methods: We obtained data on prostate cancer associated SNPs from the GWAS catalog (https://www.ebi.ac.uk/gwas) and from reports that were not included in the catalog. Using an Ancient Genome Browser provided by the Max Plank Institute (https://www.eva.mpg.de/genetics/genomeprojects/neandertal/index.html), we determined whether SNPs on chromosomes 2, 8 and 22 were present in African, Neanderthal or Denisovan genomes. Based on the results, we inferred that SNPs were introgressed if they were present in Neanderthal or Denisovan genomes but absent from African genomes. Results: 49, 59 and 17 prostate cancer SNPs were reported in chromosomes 2, 8 and 22 respectively. 23/49 in ch2, 25/59 in ch8 and 9/17 in ch22 were present in Neanderthal and or Denisovan genomes. SNPs in ch2 (rs13403657, rs12621278) and ch8 (rs7825414) were present in Neanderthal or Denisovan genomes but absent in African genomes. These SNPs lie in regions that have previously been reported to harbor introgressed DNA. Conclusion: Our analyses identified prostate cancer associated SNPs that are likely to have been introgressed into present day non-Africans by extinct Neanderthal and Denisovan ancestors. Phenotypic changes caused by introgressed DNA could be contributing to racial disparities in prostate cancer in present day humans. Citation Format: Evi O. Useh, Suresh Venugopal, Chidi N. Molokwu. Exploring the contribution of introgressed ancient DNA to prostate cancer racial disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 782.

Abstract 2497: Inositol Polyphosphate 4-Phosphatase Type-II B protects mice from benign prostatic hyperplasia

Abstract BPH is the most common tumor-like condition that afflicts more than 50% of men between the ages of 51-60 and over 90% in men older than 80. While connection between obesity and BPH is well established, the driving signaling pathways are not clear. BPH is a nonmalignant enlargement of prostate epithelium that requires androgen receptor (AR) signaling. INPP4B and EZH2 are highly expressed in prostate epithelium where they regulate AR signaling and play an important role in prostate cancer etiology. EZH2 is an epigenetic silencer that methylates histone H3 on K9 and K27 residues and INPP4B is a dual specificity phosphatase that dephosphorylates PI(3,4)P2 and PI(4,5)P2, membrane lipids that activate Akt and PKC signaling pathways respectively. We discovered that Inpp4b-/- male mice develop BPH at 3 months old of age and subsequently prostate intraepithelial neoplasia (PIN) when fed high fat diet. While expression of AR in the prostates of these mice is similar, AR activity is reduced. The loss of INPP4B caused reduction in EZH2 protein levels in prostate cancer cell lines and in mouse prostate. Inhibition of Akt and PKC signaling reduced EZH2 levels in ventral and dorsolateral prostate lobes of Inpp4b-/- males, suggesting that INPP4B upregulates EZH2 levels by suppressing Akt and PKC signaling pathways. Consistent with decline in EZH2 levels, Inpp4b-/- males have reduced levels of H3K27me3 and H3K9me2 in the ventral prostate, and high fat diet exacerbated this phenotype. Our data suggests that INPP4B modulates epigenetic profile of prostate epithelium by stabilizing EZH2 levels. Both loss of INPP4B and high fat diet treatment lead to decline in EZH2 levels and activity and contribute to development of BPH in mouse model. Citation Format: Yasemin Ceyhan, Manqi Zhang, Irina U. Agoulnik. Inositol Polyphosphate 4-Phosphatase Type-II B protects mice from benign prostatic hyperplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2497.

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective.

Background: The etiology of benign prostatic hyperplasia and prostate cancer are unknown, with ageing being the greatness risk factor. Methods: This new perspective evaluates the available interdisciplinary evidence regarding prostate ageing in terms of the cell biology of regulation and homeostasis, which could explain the timeline of evolutionary cancer biology as degenerative, inflammatory and neoplasm progressions in these multifactorial and heterogeneous prostatic diseases. Results: This prostate ageing degeneration hypothesis encompasses the testosterone-vascular-inflamm-ageing triad, along with the cell biology regulation of amyloidosis and autophagy within an evolutionary tumorigenesis microenvironment. Conclusions: An understanding of these biological processes of prostate ageing can provide potential strategies for early prevention and could contribute to maintaining quality of life for the ageing individual along with substantial medical cost savings.

Prostate cancer knowledge gaps among community stakeholders in rural Nigeria: implications for seeking screening.

In Nigeria, knowledge about prostate cancer (PCa) is poor, so are the availability, accessibility, and utilization of PCa screening services. Poor knowledge increases the burden of disease, this is more so in rural settings. PCa, being gender-specific, has underlying cultural connotations. There is a dearth of evidence on the rural-cultural understanding of PCa onset. The study examined community stakeholders' knowledge, risk perception, as well as the perceived barriers to seeking PCa screening. Rosenstock's Health Belief Model provided the theoretical framing for the study. The study design was descriptive and a cross-sectional approach to the social constructionist ideas of the qualitative tradition was adopted. There were twenty-one interviews with purposively selected community stakeholders; Fourteen key informant (traditional healers and medical doctors) interviews and seven In-depth Interviews (traditional leaders) held in the Ijebu culture cluster of Ogun State, Nigeria. Narratives were analyzed based on the following theoretical themes: knowledge, risk perception, and perceived barriers to PCa screening. These themes derived their structures from content-analyzed findings. Results show that traditional healers and leaders have limited scientific knowledge of PCa etiology. Folk beliefs form the basis of PCa knowledge among most stakeholders. However, all stakeholders consider PCa a threat to men. The cultural sense of 'maleness' and access to appropriate information about PCa are essential approaches to establishing perceived threat/susceptibility. Cancer health education and distance of screening facilities are primary barriers to seeking screening. Stakeholders' knowledge of PCa and PCa screening should be improved by educating them and developing integrative community engagement strategies.

Knowledge of prostate cancer presentation, etiology, and screening practices among women: a mixed-methods systematic review

BackgroundWith the burden of prostate cancer, it has become imperative to exploit cost-effective ways to tackle this menace. Women have demonstrated their ability to recognize early cancer signs, and it is, therefore, relevant to include women in strategies to improve the early detection of prostate cancer. This systematic review seeks to gather evidence from studies that investigated women’s knowledge about (1) the signs and symptoms, (2) causes and risk factors, and (3) the screening modalities of prostate cancer. Findings from the review will better position women in the fight against the late detection of prostate cancer.MethodsThe convergent segregated approach to the conduct of mixed-methods systematic reviews was employed. Five databases, namely, MEDLINE (EBSCOhost), CINAHL (EBSCOhost), PsycINFO (EBSCOhost), Web of Science, and EMBASE (Ovid), were searched from January 1999 to December 2019 for studies conducted with a focus on the knowledge of women on the signs and symptoms, the causes and risk factors, and the screening modalities of prostate cancer.ResultsOf 2201 titles and abstracts screened, 22 full-text papers were retrieved and reviewed, and 7 were included: 3 quantitative, 1 qualitative, and 3 mixed-methods studies. Both quantitative and qualitative findings indicate that women have moderate knowledge of the signs and symptoms and the causes and risk factors of prostate cancer. However, women recorded poor knowledge about prostate cancer screening modalities or tools.ConclusionsModerate knowledge of women on the signs and symptoms and the causes and risk factors of prostate cancer was associated with education. These findings provide vital information for the prevention and control of prostate cancer and encourage policy-makers to incorporate health promotion and awareness campaigns in health policies to improve knowledge and awareness of prostate cancer globally.Systematic review registrationOpen Science Framework (OSF) registration DOI: https://doi.org/10.17605/OSF.IO/BR456

Copy number signature analysis tool and its application in prostate cancer reveals distinct mutational processes and clinical outcomes.

Genome alteration signatures reflect recurring patterns caused by distinct endogenous or exogenous mutational events during the evolution of cancer. Signatures of single base substitution (SBS) have been extensively studied in different types of cancer. Copy number alterations are important drivers for the progression of multiple cancer. However, practical tools for studying the signatures of copy number alterations are still lacking. Here, a user-friendly open source bioinformatics tool "sigminer" has been constructed for copy number signature extraction, analysis and visualization. This tool has been applied in prostate cancer (PC), which is particularly driven by complex genome alterations. Five copy number signatures are identified from human PC genome with this tool. The underlying mutational processes for each copy number signature have been illustrated. Sample clustering based on copy number signature exposure reveals considerable heterogeneity of PC, and copy number signatures show improved PC clinical outcome association when compared with SBS signatures. This copy number signature analysis in PC provides distinct insight into the etiology of PC, and potential biomarkers for PC stratification and prognosis.

Association between environmental quality and prostate cancer stage at diagnosis.

Prostate cancer (PC) etiology is up to 57% heritable, with the remainder attributed to environmental exposures. There are limited studies regarding national level environmental exposures and PC aggressiveness, which was the focus of this study METHODS: SEER was queried to identify PC cases between 2010 and 2014. The environmental quality index (EQI) is a county-level metric for 2000-2005 combining data from 18 sources and reports an overall ambient environmental quality index, as well as 5 environmental quality sub-domains (air, water, land, built, and sociodemographic) with higher values representing lower environmental quality. PC stage at diagnosis was determined and, multivariable logistic regression models which adjusted for age at diagnosis (years) and self-reported race (White, Black, Other, Unknown) were used to test associations between quintiles of EQI scores and advanced PC stage at diagnosis. The study cohort included 252,164 PC cases, of which 92% were localized and 8% metastatic at diagnosis. In the adjusted regression models, overall environmental quality EQI (OR 1.20, CI 1.15-1.26), water EQI (OR: 1.34, CI: 1.27-1.40), land EQI (OR: 1.35, CI: 1.29-1.42) and sociodemographic EQI (OR: 1.29, CI: 1.23-1.35) were associated with metastatic PC at diagnosis. For these domains there was a dose response increase in the OR from the lowest to the highest quintiles of EQI. Black race was found to be an independent predictor of metastatic PC at diagnosis (OR: 1.36, CI: 1.30-1.42) and in stratified analysis by race; overall EQI was more strongly associated with metastatic PC in Black men (OR: 1.53, CI: 1.35-1.72) compared to White men (OR: 1.18, CI: 1.12-1.24). Lower environmental quality was associated with advanced stage PC at diagnosis. The water, land and sociodemographic domains showed the strongest associations. More work should be done to elucidate specific modifiable environmental factors associated with aggressive PC.

Phosphorylation of the androgen receptor at Ser81 is co-sustained by CDK1 and CDK9 and leads to AR-mediated transactivation in prostate cancer.

Androgen receptor (AR) is the principal molecule in prostate cancer (PCa) etiology and therapy. AR re‐activation still remains a major challenge during treatment of castration‐resistant prostate cancer (CRPC) tumors that relapse after castration therapies. Recent reports have indicated the enrichment of Ser81‐phosphorylated AR (pS81) in the nucleus of CRPC cells, and CDK1 and CDK9 as the kinases phosphorylating AR at S81. In the current study we showed that pS81 is preferentially localized in the nucleus in both rapid biopsy metastatic CRPC samples and PCa xenografts, and nuclear pS81 localization is correlated with AR transactivation in tumor xenografts. Chromatin immunoprecipitation (ChIP) analysis demonstrated an alignment of S81 phosphorylation and AR‐mediated transactivation with the chromatin locus openness. Moreover, pS81‐specific ChIP‐Seq showed a disproportional occupancy of pS81 on AR‐activated promoters, while 3C‐ChIP assays further indicated an enrichment of pS81 at the PSA enhancer‐promoter loop, a known AR activating hub. In the latter, CDK9 was shown to modulate the transactivation of the AR and RNA Pol II. Indeed, ChIP and re‐ChIP assays also confirmed that AR‐dependent activation of the PSA enhancer and promoter mediated by pS81 was coupled with activation of Pol II and the pTEFb complex. Mechanistically, we determined that CDK1 and CDK9 sustained the pS81 AR modification in the soluble and chromatin‐bound fractions of PCa cells, respectively. Finally, we demonstrated that CDK1 activity was maintained throughout the cell cycle, and that CDK1 inhibitors restored androgen sensitivity in CRPC tumor cells. Based on these findings, CDK1 and CDK9 could be targeted as pS81 kinases in patients with CRPC, either alone or in conjunction with direct AR antagonists.

Ectopically Expressed Olfactory GPCRs OR51E1/2: Ligand Specificity, Signal Transduction, and Cytostatic and Cytotoxic Activity

Olfactory receptors (ORs) are the largest family of G protein-coupled receptors: there are ~380 ORs in humans and ~1,000 in mice. This family was originally cloned from the nasal epithelium, but several years ago, expression of many OR genes was detected in the airways, gut, blood vessels, brain, and other organs. These GPCRs are referred to as ectopic ORs (eORs). Understanding eOR function has lagged behind that of other GPCRs, and the majority of ORs remain to be orphan receptors. One reason for this delay is that the expression of functionally active ORs has not been technically possible for many years. In contrast to the most other Class A GPCRs, which can be produced using standard methods such as transient transfection, stability and trafficking ORs requires special chaperones and/or modification with unique signal peptides. Difficulties with detection and functional analysis of both endogenous and overexpressed eORs caused many controversies, and overall, this vast and potentially interesting family of GPCRs has been grossly understudied. Here, we investigated two eORs, OR51E1 and OR51E2, which due to their marked upregulation in prostate cancer are also known as “prostate-specific G protein-coupled receptors” (PSGR2 and PSGR, respectively). To investigate their signaling and effects on proliferation and survival we developed an inducible expression system in a prostate cancer cell line LNCaP. The robust expression and trafficking of ORs allowed us to analyze their function using cAMP, Ca2+, protein phosphorylation and other assays. Consistent with previous studies, OR51E1 stimulated adenylyl cyclase in response to treatment by short- to medium-chain organic acids (C3-C9) an some branched aliphatic acids. OR51E2 responded to acetate and propionate, but not to the longer chain organic acids. Other putative ligands mentioned in the literature did not have activity. Stimulation of LNCaP cells with butyrate inhibited their growth, and the knockdown of the endogenous OR51E1 negated this cytostatic effect. Interestingly, induced overexpression of OR51E1 or OR51E2 suppressed LNCaP cell proliferation. Overexpression of OR2AT4, beta2-adrenergic receptor or treatment of cells with forskolin did not suppress cell proliferation, indicating that rise in cAMP is not sufficient to induce cytostasis. These findings indicate that like other GPCRs, eORs can signal via more than one G protein pathway. Overexpression of OR51E1 caused upregulation of cytostatic and cell death markers including p27, p21, and p53, strongly increased annexin V staining and stimulated ERK1/2. OR51E1 had no effect on proliferation of HEK293 cells, indicating that cytotoxicity of OR51E1/2 is specific for LNCaP cells. Elucidating this mechanism will contribute to understanding etiology of prostate cancer and may illuminated these two and possibly other eORs as future therapeutic targets.

Stigma, beliefs and perceptions regarding prostate cancer among Black and Latino men and women

BackgroundHealth disparities in prostate cancer (PC) are thought to reflect the complex interplay of socioeconomics, environment and biology. The potential impact of beliefs and perceptions about PC among Black and Latino populations on clinical disparities are not well understood. This qualitative study was conducted to assess current prevalent and pervasive stigma, beliefs and perceptions regarding PC among Blacks and Latinos living in a large metropolitan area, thereby identifying potentially modifiable barriers to care.MethodsQualitative data were collected through four separate focus groups of self-identified Black and Latino adult men and women living in Philadelphia to better understand their perceptions of PC diagnosis, screening and treatment. Each focus group was single-sex and conducted by racial/ethnic group in order to assess possible differences in beliefs about PC based on gender and racial/ethnic affiliation. Audio recordings were transcribed verbatim by trained research assistants and qualitative data analysis was conducted using modified grounded theory.ResultsThere were a total of 34 participants: 19 Hispanics/Latinos and 15 Blacks, with equal numbers of men and women (n=17). Median age was 57 years (range: 18 to 85 years). Dominant themes that emerged with respect to PC diagnosis included the stigma surrounding this condition and the perceived role of an “unhealthy lifestyle” and certain sexual behaviors as risk factors for PC development. While the majority of participants acknowledged the importance of PC screening and early detection, discussion centered around the barriers to both the interest in seeking medical care and the likelihood of securing it. These barriers included misunderstanding of PC etiology, distrust of the medical profession, and financial/access limitations. Men expressed substantial confusion about PC screening guidelines. In the Black female group, the role of faith and religion in the course of disease was a major theme. Both Black and Latina females discussed the role of fear and avoidance around PC screening and treatment, as well as the prevalence of misinformation about PC in their familial and social communities.ConclusionBlack and Latino focus groups revealed the existence of cultural beliefs, misunderstandings and fears pertaining to PC which could influence health-related behaviors. Some themes were common across groups; others suggested racial and gender predilections. Future targeted efforts focused on directly addressing prevalent misperceptions among underserved communities in urban settings could help to improve health literacy and equity in PC outcomes in these populations.

Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems.

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.

The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries.

Simple SummaryReal-world data (RWD), i.e., data reflecting normal clinical practice collected outside the constraints of randomised controlled trials, provide important insights into our understanding of prostate cancer and its management. Clinical cancer registries are an important source of RWD. Depending on their scope and the potential linkage to other data sources, registry-based data can be utilised to address a variety of questions including risk factors, healthcare utilisation, treatment effectiveness, adverse effects, disparities in healthcare access, quality of care and healthcare economics. This review describes the various registry-based RWD sources for prostate cancer research in Sweden (namely the National Prostate Cancer Register, the Prostate Cancer data Base Sweden (PCBaSe) and the Patient-overview Prostate Cancer) and documents their utility for better understanding prostate cancer aetiology and improving clinical care.Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

Dietary Factors and Prostate Cancer Development, Progression, and Reduction.

Due to the constantly increasing number of cases, prostate cancer has become one of the most important health problems of modern societies. This review presents the current knowledge regarding the role of nutrients and foodstuff consumption in the etiology and development of prostate malignancies, including the potential mechanisms of action. The results of several in vivo and in vitro laboratory experiments as well as those reported by the clinical and epidemiological research studies carried out around the world were analyzed. The outcomes of these studies clearly show the influence of both nutrients and food products on the etiology and prevention of prostate cancer. Consumption of certain nutrients (saturated and trans fatty acids) and food products (e.g., processed meat products) leads to the disruption of prostate hormonal regulation, induction of oxidative stress and inflammation, and alteration of growth factor signaling and lipid metabolism, which all contribute to prostate carcinogenesis. On the other hand, a high consumption of vegetables, fruits, fish, and whole grain products exerts protective and/or therapeutic effects. Special bioactive functions are assigned to compounds such as flavonoids, stilbenes, and lycopene. Since the influence of nutrients and dietary pattern is a modifiable risk factor in the development and prevention of prostate cancer, awareness of the beneficial and harmful effects of individual food ingredients is of great importance in the global strategy against prostate cancer.

Pilot Study on the Locoregional Demographics of Prostate Cancer in River State, Nigeria.

The aetiology of prostate cancer is a subject of intense research and has been attributed to several risk factors. Geographical variations have also been observed with high incidence in western countries and rising rates in developing countries. This study aims to evaluate the locoregional distribution of histologically confirmed prostate cancer patients and discuss the risk factors for the observed variations according to their Local Government Areas (LGA) in Rivers State. This is a descriptive retrospective study on patients with histologically confirmed prostate cancer from three hospitals that take urology referrals over 10years. The patient's hospital records were obtained, and records of their ages, permanent place of residence, prostate biopsy histopathology reports, and Gleason's scores were extracted. These data were collated and analyzed using SPSS version 20. There were 278 patients managed over a 10year period with a mean age of 68.39years+_10.06. Prostate cancer was the commonest in the 60-69year age group (37.1%), followed by the 70-79year range. The high-risk, poorly differentiated cancer (Gleason 8-10; ISUP 4,5) was the commonest, followed by the intermediate-risk cancers (Gleason 7; ISUP 2,3). Port Harcourt (41.0%) and ObiaAkpo (36.0%) Local Government Areas (LGAs) in Port Harcourt City had the highest frequencies of prostate cancer. There was no relationship between age and Gleason's score in the men. Prostate cancer appears more common in the LGAs in Port Harcourt City compared to the semi-urban and rural LGAs in Rivers State. High-grade cancers are more frequent both in rural and urban LGA. High Gleason score cancers appear more frequently in the metropolitan Port Harcourt City than rural LGAs.

Gene Expression Pathways in Prostate Tissue Associated with Vigorous Physical Activity in Prostate Cancer.

Men engaged in high physical activity have lower risks of advanced and fatal prostate cancer. Mechanisms underlying this association are not well understood but may include systemic and tumor-specific effects. We investigated potential mechanisms linking physical activity and gene expression in prostate tissue from men with prostate cancer. We included a subset of 118 men in the Health Professionals Follow-up Study diagnosed with prostate cancer between 1986 and 2005 with whole-transcriptome gene expression profiling on tumor and adjacent normal prostate tissue and physical activity data. Long-term vigorous physical activity was self-reported as the average time spent engaged in various forms of recreational physical activity at baseline and biennially until prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and Hallmark gene sets to identify pathways with differential expression based on vigorous physical activity. In adjacent normal tissue, we identified 25 KEGG gene sets enriched (downregulated) in the highest compared with lowest quintile of vigorous physical activity at an FDR <0.10, including a number of cancer- and immune-related pathways. Although no gene sets reached statistical significance in tumor tissue, top gene sets differentially expressed included TGF beta, apoptosis, and p53 signaling pathways. These findings suggest that physical activity may influence the tumor microenvironment. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to lethal prostate cancer. Identification of gene expression alterations in the prostate associated with physical activity can improve our understanding of prostate cancer etiology.