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Abstract Introduction Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome‐wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results Around 5,139 differentially methylated CpG‐sites (q 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune‐related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors’ total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG‐sites (q .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA‐C, and ADCYAP1, have previously been linked to tumor progression in PCa. Conclusion Several differentially methylated genes involved in immune‐oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American‐specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

After the COVID-19 pandemic, the field of higher education increased its attention on quality distance learning for traditional and non-traditional adult learners. While the world saw an increase in online education enrollment as a result of the pandemic, non-traditional adult learners have historically relied on this method of education delivery to support their success in the collegiate setting. As the field of human service education supports the offering of distance learning instruction, it is vital for human service educators to consider the National Standards for Quality Online Teaching when educating adult learners. The authors of this article provide an overview of the needs of non-traditional adult learners post COVID-19; and suggest that the National Standards for Quality Online teaching be considered when delivering human service education in CSHSE accredited classrooms to this population.

Social isolation and disability are established risk factors for poor nutrition. We aimed to assess whether social isolation is associated with diet quality specifically among adults with disabilities.This cross-sectional analysis used data from the National Health and Nutrition Examination Survey, 2013–2018. Adults with a disability, who were not pregnant, breastfeeding, or missing dietary intake data were included (n = 5,167). Disability was defined as a physical functioning limitation based on difficulty with any activities of daily living, instrumental activities of daily living, lower extremity mobility activities, or general physical activities. The Healthy Eating Index (HEI)-2015 measured diet quality; higher scores correspond to higher diet quality. We computed a social isolation index by summing single status, living alone, and two social engagement difficulty measures (one point for each component met; maximum 4 points). Multivariable linear regression, controlling for demographic and health covariates, estimated differences in HEI scores for dietary intake data, by social isolation score.Over half of HEI scores were

Abstract Background HIV pre-exposure prophylaxis (PrEP) is a medication that prevents the acquisition of HIV. It has been targeted towards men who have sex with men (MSM). Since its introduction there have been concerns raised around changes in sexual behaviour such as increased condomless anal intercourse (CAI), leading to an elevation in sexually transmitted infections (STIs). With antimicrobial resistant strains of STIs rising, there are concerns that PrEP may be contributing to this growth. This study aims to understand how MSM conceptualise the relationship between PrEP, STIs and antimicrobial resistance (AMR). Methods Twenty semi-structured interviews were conducted online using Zoom. Participants include a mix of PrEP related experiences (never used, currently use, previously used). Reflexive thematic analysis was undertaken by the lead author with 10% of transcripts double coded. Results MSM in Wales have positive views and a good knowledge of PrEP and awareness of bacterial STIs. PrEP is perceived by many to lead to a reduction in condom use and increase in STIs but reported condom use behaviours presented to be stable in terms of PrEP initiation. PrEP use is influenced by increased concern for HIV and minimal concern for bacterial STIs. Awareness of AMR STIs was lacking. Conclusions There is a belief that PrEP use will lead to an increase in STI rates through reduced condom use, despite reported behaviours often being stable in relation to PrEP initiation, PrEP stigma may be influencing this dichotomy. Concern and awareness for resistant STIs is low, with little association to PrEP.

Human parechovirus-3 (HPeV-3) infection is one of the differential diagnoses of neonatal meningoencephalitis. A 13-day-old full-term female neonate presented with a seizure. Brain MRI showed classic imaging findings of the meningoencephalitis which was confirmed on cerebrospinal fluid analysis. Contribution: The HPeV-3 is an emerging pathogen for neonatal meningoencephalitis. The case in this study is unique with classic imaging findings, which are not routinely encountered in day-to-day practice. This case raises reader awareness.

Abstract Background The COVID-19 pandemic and its associated restrictions stopped people freely engaging in sexual behaviour. We explored sexual behaviour amongst men who have sex with men (MSM) using mixed methods during the multiple lockdowns in Wales. Methods An online survey was advertised on social media platforms (focusing on Welsh LGBT groups), from June 2020 to July 2020. MSM over 16 years were invited to take part if they were resident in Wales. Qualitative interviews were undertaken as part of a study examining knowledge and awareness of sexual health. Interviews were conducted between September 2020 and February 2021 via Zoom©. Interview data was analysed thematically and integrated with survey data. Results The survey received 70 responses, 60% (n = 42) reported not having sexual activity during lockdown. Restrictions altered the number of new sexual partners per week with over 80% (n = 56) not having any new sexual partners for the 12 weeks of the first lockdown. However, as the weeks progressed following the first lockdown there was an increase in the number of new sexual partners. Interview data indicated that the COVID-19 pandemic had a large impact on reducing sexual behaviour with other MSM in Wales. ‘Lockdown fatigue’ was viewed to result in different levels of adherence to the lockdown rules depending on the lockdown being discussed. Of those engaging in sex outside the rules, ‘shame’ was commonly reported. The restrictions were believed to have a positive impact on reducing the spread of sexually transmitted infections. Conclusions The COVID-19 pandemic and associated restrictions had a significant impact on sexual behaviours among MSM in Wales, with the majority fully adhering to the lockdown rules. Although the population were largely compliant with the lockdown restrictions, lockdown fatigue may suggest that any future lockdowns might not have the same effect.

Background: Urinary tract infection (UTI) affects half of women at least once in their lifetime. Current diagnosis involves urinary dipstick and urine culture, yet both methods have modest diagnostic accuracy, and cannot support decision-making in patient populations with high prevalence of asymptomatic bacteriuria, such as older adults. Detecting biomarkers of host response in the urine of hosts has the potential to improve diagnosis. Objectives: To synthesise the evidence of the diagnostic accuracy of novel biomarkers for UTI, and of their ability to differentiate UTI from asymptomatic bacteriuria. Design: A systematic review. Data Sources and Methods: We searched MEDLINE, EMBASE, CINAHL and Web of Science for studies of novel biomarkers for the diagnosis of UTI. We excluded studies assessing biomarkers included in urine dipsticks as these have been well described previously. We included studies of adult patients (≥16 years) with a suspected or confirmed urinary tract infection using microscopy and culture as the reference standard. We excluded studies using clinical signs and symptoms, or urine dipstick only as a reference standard. Quality appraisal was performed using QUADAS-2. We summarised our data using point estimates and data accuracy statistics. Results: We included 37 studies on 4009 adults measuring 66 biomarkers. Study quality was limited by case-control design and study size; only 4 included studies had a prospective cohort design. IL-6 and IL-8 were the most studied biomarkers. We found plausible evidence to suggest that IL-8, IL-6, GRO-a, sTNF-1, sTNF-2 and MCR may benefit from more rigorous evaluation of their potential diagnostic value for UTI. Conclusions: There is insufficient evidence to recommend the use of any novel biomarker for UTI diagnosis at present. Further evaluation of the more promising candidates, is needed before they can be recommended for clinical use.

Introduction There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke.Methods and analysis We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010–2020. Individuals will need to be aged 30–100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in ‘baseline’ periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios.Ethics and dissemination Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.

Microbiological data are used as indicators of infection, for diagnosis, and the identification of antimicrobial resistance in trials of antimicrobial stewardship interventions. However, several problems have been identified in a recently conducted systematic review (e.g., inconsistency in reporting and oversimplified outcomes), which motivates the need to understand and improve the use of these data including analysis and reporting. We engaged key stakeholders including statisticians, clinicians from both primary and secondary care, and microbiologists. Discussions included issues identified in the systematic review and questions about the value of using microbiological data in clinical trials, perspectives on current microbiological outcomes reported in trials, and alternative statistical approaches to analyse these data. Various factors (such as unclear sample collection process, dichotomising or categorising complex microbiological data, and unclear methods of handling missing data) were identified that contributed to the low quality of the microbiological outcomes and the analysis of these outcomes in trials. Whilst not all of these factors would be easy to overcome, there is room for improvement and a need to encourage researchers to understand the impact of misusing these data. This paper discusses the experience and challenges of using microbiological outcomes in clinical trials.

Abstract Background Social support has an important role in successful weight loss. The aim of this study was to assess the feasibility and acceptability of an app-, web- and social support-based intervention in supporting adults with obesity to achieve weight loss. Methods The intervention and evaluation methods were tested in a feasibility randomised controlled trial. Adults in the Greater Glasgow and Clyde Health Board area of Scotland with a body mass index ≥ 30 kg/m2 were recruited and randomised 2:1 (intervention to control). The feasibility and acceptability of the intervention and trial methods were assessed against pre-specified progression criteria, via process, economic and outcome evaluation. Three primary outcomes were explored: BMI, diet and physical activity, as well as a number of secondary outcomes. The intervention group had access to the HelpMeDoIt! intervention for 12 months. This encouraged them to (i) set goals, (ii) monitor progress and (iii) harness social support by inviting ‘helpers’ from their existing social network. The control group received a healthy lifestyle leaflet. Results One hundred and nine participants were recruited, with 84 participants (77%) followed-up at 12 months. The intervention and trial methods were feasible and acceptable. Participants and helpers were generally positive. Of the 54 (74%) participants who downloaded the app, 48 (89%) used it. Interview data indicated that HelpMeDoIt! promoted social support from existing social networks to support weight loss. This support was often given outside of the app. Outcomes were compared using linear regression models, with randomised group, the baseline measurement of the outcome, age and gender as predictor variables. These analyses were exploratory and underpowered to detect effects. However, all pre-specified primary outcome effects (BMI, diet and physical activity) had wide confidence intervals and were therefore consistent with clinically relevant benefits. Objective physical activity measures perhaps showed most potential (daily step count (p = 0.098; 1187 steps [− 180, 2555])) and sedentary time (p = 0.022; − 60.8 min [− 110.5, − 11.0]). However, these outcomes were poorly completed. Conclusions The study demonstrated that a novel social support intervention involving support from participants’ close social networks, delivered via app and website, has potential to promote weight loss and is feasible and acceptable. Trial registration ISRCTN, ISRCTN85615983 . Registered 25 September 2014

Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.

Background: Finding solutions to rising levels of obesity continues to be a major public health focus. Social support has an important role in successful weight loss, and digital interventions can reach a large proportion of the population at low cost. Objective: To develop and assess the feasibility and acceptability of an application (app), web- and social support-based intervention in supporting adults with obesity to achieve weight loss goals. Design: Stage 1 – intervention development phase involved three focus groups (n = 10) with users, and think-aloud interviews and field testing with another group (n = 28). Stage 2 – the intervention and evaluation methods were explored in a feasibility randomised controlled trial with economic and process evaluation. Setting: Greater Glasgow and Clyde, UK. Participants: Adults with a body mass index of ≥ 30kg/m2 who owned a smartphone and were interested in losing weight were randomised 2 : 1 (intervention : control) and followed up at 12 months. Recruitment took place in April–October 2016. Interventions: The intervention group had access to HelpMeDoIt! for 12 months. This encouraged them to (1) set goals, (2) monitor progress and (3) harness social support by inviting ‘helpers’ from their existing social network. The control group received a healthy lifestyle leaflet. Main outcome measures: Data from stage 1 informed the intervention design. Key measures in stage 2 assessed the feasibility and acceptability of the intervention and trial methods against prespecified progression criteria. Three primary outcomes were explored: body mass index, diet and physical activity. Secondary outcomes included weight, waist and hip circumference, social support, self-efficacy, motivation, mental health, health-related quality of life, NHS resource use, participant-borne costs and intervention costs. Qualitative interviews with participants (n = 26) and helpers (n = 9) explored the feasibility and acceptability of the trial methods and intervention. Results: Stage 1 produced (1) a website that provided evidence-based information for lifestyle change and harnessing social support, and (2) an app that facilitated goal-setting, self-monitoring and supportive interaction between participants and their helper(s). Progression criteria were met, demonstrating that the intervention and trial methods were feasible and acceptable. A total of 109 participants (intervention, n = 73; control, n = 36) were recruited, with 84 participants (77%: intervention, 71%; control, 89%) followed up at 12 months. Data were successfully collected for most outcome measures (≥ 82% completion). Participants and helpers were generally positive, although helper engagement with the app was low. Of the 54 (74%) participants who downloaded the app, 48 (89%) used it twice or more, 28 helpers enrolled via the app, and 19 (36%) participants interacted with their helper(s) via the app. Interview data indicated that HelpMeDoIt! prompted support from helpers that often occurred without the helpers using the app. Limitations: Early technical problems meant that some participants and helpers had difficulty accessing the app. Ethical constraints meant that we were unable to contact helpers directly for interview. Conclusions: The HelpMeDoIt! study demonstrated that a weight loss intervention delivered via an app and a website is feasible and acceptable. Progression criteria were met, supporting further evaluation of the intervention. Future work: To further explore (1) the motivation and engagement of helpers, (2) the programme theory and (3) the effectiveness and cost-effectiveness of the intervention. Trial registration: Current Controlled Trials ISRCTN85615983. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 3. See the NIHR Journals Library website for further project information.

Background Guidelines recommend the prompt diagnosis and treatment of UTI in young children to reduce the risk of renal scarring and possible long-term complications. However, the evidence for this association is weak and has been questioned. There is an urgent need to clarify this as the correct approach to urine sampling and diagnosis of UTI in children hinges on this association. Main Aim Determine outcomes following UTI in childhood (1 microbiologically confirmed UTI (mcUTI) aged 1 mcUTI. The overall prevalence of renal scarring in the cohort by age 7 was 0.16%; 1.26% in those with >1 mcUTI; 0.08% in those with no mcUTI. The unadjusted odds ratio (OR) was 16.62 (12.91-21.39) and adjusted 3.64 (2.57-5.14). Among the group with >1 mcUTI, predictors of renal scarring were VUR, younger age of first UTI, and greater number of UTIs 1 mcUTI was lower than expected. Possible explanations include poor coding in routine data, different patient populations or missed renal scarring diagnoses. We are currently validating our results using radiology data. If renal scarring diagnoses are being missed, a more proactive urine sampling and imaging strategy may be indicated. However, if renal scarring rates are low following UTI, this may not be necessary.

Introduction Researchers are increasingly using routinely collected data in addition to, or instead of, other data collection methods. The UK government continues to invest in research centres to encourage use of these data, and trials and cohort studies utilise data linkage methods in the follow-up of participants. This does not come without its limitations and challenges, such as data access delays. Objective This paper outlines the challenges faced by three projects utilising individual-level routinely-collected linked data for the longer-term follow-up of participants. Methods: These studies are varied in design, study population and data providers. One researcher was common to the three studies and collated relevant study correspondence, formal documentary evidence such as data sharing agreements and, where relevant, meeting records to review. Key themes were identified and reviewed by other members of the research teams. Mitigating strategies were identified and discussed with a data provider representative and a broader group of researchers to finalise the recommendations presented. Results The challenges discussed are grouped into five themes: Data application process; Project timelines; Dependencies and considerations related to consent; Information Governance; Contractual. In presenting our results descriptively we summarise each case study, identify the main cross-cutting themes and consider the potential for mitigation of challenges. Conclusions We make recommendations that identify responsibilities for both researchers and data providers for mitigating and managing data access challenges. A continued conversation within the research community and with data providers is needed to continue to enable researchers to access and utilise the wealth of routinely-collected data available. The suggestions made in this paper will help researchers be better prepared to deal with the challenges of applying for data from multiple data providers.

Introduction The method used to define a GP-consultation using routine data will vary depending on the data source and research question. However, without consensus the approach will be tackled by numerous researchers and invariably result in different definitions. The LUCI study is assessing outcomes of childhood UTI using routine data sources. Objectives and Approach We are interested in GP urine sampling rate and re-consultation rate. The GP dataset includes multiple clinical (acute, routine monitoring, prescribing, results) and administrative codes. A GP consultation therefore needed to be defined. GP read code frequencies for our study cohort of children were produced. One researcher reviewed the codes that represented 80% of the data and classified them as a consultation or not. Where there was uncertainty this was independently reviewed by two clinicians and discrepancies agreed by the management team. Results We will present the decisions and assumptions made for this study in defining a GP consultation. 25,623 Read Codes represented the consultations for our study cohort of which 460 codes represented 80% of the consultations. The remaining 20% of codes represented

Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation and the risk of hormone-related cancers. Here we evaluated whether single nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism and regulation (N=1100), as well as SNPs associated with circulating sex steroid concentrations as identified by genome-wide association studies (N=17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction=4.0x10-5; q-value=0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR=0.62 95% CI: 0.41, 0.93), and high use of dicamba (OR=0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic or antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.

Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15) (P-interaction= 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction= 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.

Background: Studies have identified associations between neighborhood disadvantage (ND), which is more likely to affect African American (AA) individuals, and aggressive prostate cancer. Thus, ND may contribute to prostate cancer disparities. However, it is unknown what ND components drive aggressive disease and whether associations vary by race. Methods: We evaluated associations between aggressive prostate cancer and four ND metrics--Area Deprivation Index (ADI), validated Bayesian Neighborhood Deprivation Index (NDI), racial isolation (RI) index, and historical redlining, and whether these factors interacted with race, among men with prostate cancer treated at the University of Maryland Greenebaum Comprehensive Cancer Center (2004-2021). Results: We included 1,458 men (698 European American and 760 AA). AA men were more likely to experience ND. In adjusted models, the ADI, RI, and redlining were significantly associated with aggressive versus nonaggressive prostate cancer overall [ADI, OR for one SD increase = 1.14, 95% confidence interval (CI), 1.00-1.30; RI, OR = 1.27, CI, 1.07-1.51; redlining, OR = 1.77; CI, 1.23-2.56] and among AA men. The NDI was associated with aggressive prostate cancer among AA men (OR = 1.32, 95% credible interval: 1.13-1.57); percent in poverty received the largest importance weight. The ADI (P heterogeneity = 0.002) and NDI (exceedance probability heterogeneity = 98.1%) significantly interacted with race, such that associations were significantly stronger for AA men. Conclusions: We identified novel significant positive associations for racial segregation and historical redlining with aggressive prostate cancer and significant interactions between ND indices and race. [ABSTRACT FROM AUTHOR]

Introduction: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome‐wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Results: Around 5,139 differentially methylated CpG‐sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune‐related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG‐sites (q < 0.05, lΔβl >.05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA‐C, and ADCYAP1, have previously been linked to tumor progression in PCa. Conclusion: Several differentially methylated genes involved in immune‐oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American‐specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population. [ABSTRACT FROM AUTHOR]