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Purpose: Germline mutations in DNA damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. Materials and Methods: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PV/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. Results: Total of 28 PV/LPVs were identified in 30 (8.8%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.41%]), ATM (2 men [0.59%]), NBN (2 men [0.59%], and BRIP1 (2 men [0.59%]). Only one patient had HOXB13 mutation (0.29%). A lower rate of overall germline variant frequency was observed in Korean mPC compared to Caucasians (8.8% vs. 11.8%), but individual variants notably differed from Caucasian and geographically similar Japanese cohorts. PV/ LPVs in DDR genes tended to increase gradually with higher Gleason scores (GS 7, 7.1%; GS 8, 7.5%; GS 9–10, 9.9%). Conclusions: BRCA2 was the most frequently mutated gene common to different cohorts supporting its importance, but differences in variant distribution in Korean mPC underscore the need for ethnic-specific genetic models. Future ethnic-specific analyses are warranted to verify our findings. [ABSTRACT FROM AUTHOR]

Genetic alterations are one of the important known risk factors of prostate cancer. The family predisposition of breast and ovarian cancers may cause the severe progression of familial prostate cancer in some men. The association of germline mutations in BRCA1 and BRCA2 genes can cause breast cancer in almost 35% of women and 9% of men. Carriers of these pathogenic variants have a higher risk of causing prostate cancer. This study focused on the analysis of mutations causing prostate cancer around the world, associated with breast cancer susceptibility genes. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequently occurring type of malignant tumor and a leading cause of oncological death in men. PCa is very heterogeneous in terms of grade, phenotypes, and genetics, displaying complex features. This tumor often has indolent growth, not compromising the patient's quality of life, while its more aggressive forms can manifest rapid growth with progression to adjacent organs and spread to lymph nodes and bones. Nevertheless, the overtreatment of PCa patients leads to important physical, mental, and economic burdens, which can be avoided with careful monitoring. Early detection, even in the cases of locally advanced and metastatic tumors, provides a higher chance of cure, and patients can thus go through less aggressive treatments with fewer side effects. Furthermore, it is important to offer knowledge about how modifiable risk factors can be an effective method for reducing cancer risk. Innovations in PCa diagnostics and therapy are still required to overcome some of the limitations of the current screening techniques, in terms of specificity and sensitivity. In this context, this review provides a brief overview of PCa statistics, reporting its incidence and mortality rates worldwide, risk factors, and emerging screening strategies. [ABSTRACT FROM AUTHOR]

The authors reviewed and sumarised the literature about active surveillance in prostate cancer. It provides a useful reference on patient selection criteria, surveillence investigations, barriers and enablers of active surveillence and evolving technologies that will be used in the future. The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection cr iter ia and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection cr iter ia recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection. [ABSTRACT FROM AUTHOR]

DNA damage repair (DDR) pathways hold prognostic information in high-risk prostate cancer. Here, we investigated DDR in low-risk prostate cancer and demonstrated that high DDR is associated with poor clinical outcome and a distinct molecular subtype. Introduction: Understanding if divergent molecular profiles of DNA damage and repair (DDR) pathway activity, a biomarker of disease progression, exist in prostate tumors with favorable-risk features is an unmet need, which this study aim to unearth. Materials and Methods: This was a multicenter registry genome-wide expression profiling study of prospectively collected radical prostatectomy (RP) tumor samples from 2014 to 2016. DDR activity was calculated from average expression of 372 DDR genes. Consensus hierarchical clustering was used to arrive at a robust clustering solution based on DDR gene expression patterns. Genome-wide differential expression between clusters was performed, and outcomes were evaluated across expression patterns. Results: Of 5239 patients from the prospective registry, 376 had favorable-risk disease (Grade group [GG] 1 to 2, PSA prior to RP < 10ng/ml, pT2 or less). DDR activity score was correlated with prognostic genomic signatures that predict for metastatic risk (r = 0.37, P < 2e -16) and high grade groups (P < .001). High DDR activity (top-quartile) was observed in 28% of patients with favorablerisk disease. In favorable-risk disease, 3 distinct clusters with varied DDR activity emerged with consensus clustering. Cluster I (compared with cluster II-III and GG3-GG5 disease) had the highest expression of all DDR sub-pathways, MYC, PAPR1, AR, and AR activity (P < .001 for all). Furthermore, cluster I was associated with poorer metastasis-free survival (MFS) and Overall survival (OS) compared with other clusters (MFS; HR: 2.43, 95%CI, [1.22-4.83], P = .01; OS; HR: 2.77, 95%CI, [1.18-6.5], P = .01). Conclusions: Cluster I is a novel subgroup of favorable-risk disease with high DDR activity, AR activity, PARP1 and chr8q/MYC expression, and poorer MFS and OS. [ABSTRACT FROM AUTHOR]

We examined the independent and combined effects of body mass index/obesity and diabetes mellitus in relation to the NCCN prostate cancer (PCa) risk groups in a racially-diverse cohort of men from an urban medical center. We found that obesity and diabetes were associated with high-risk PCa; however, most of the association was driven by obesity. Introduction: Obesity and diabetes mellitus (DM) have been associated with prostate cancer (PCa) risk, but data examining their combined effects on aggressive PCa are sparse, particularly among non-Hispanic Black and Hispanic men. We investigated the associations of obesity and DM in relation to National Comprehensive Cancer Network (NCCN) PCa risk groups in a racially-diverse patient population. Patients and Methods: We abstracted demographic and clinical data from men who underwent radical prostatectomy at our institution between 2005 and 2019. Patients were classified into three NCCN PCa risk-groups: low, intermediate and high-risk. Logistic regression models were used to examine the independent and combined associations of body mass index (BMI)/obesity and DM with risks of intermediate and high-risk PCa, adjusting for age and race/ethnicity. Results: A total of 1303 men with PCa (average age 60 ± 6.9 years) were analyzed. The majority were non-Hispanic Black (N = 493, 38%) or Hispanic (N = 407, 31%). The prevalence of obesity (BMI = 30 kg/m 2) and DM was 29.3% (N = 382) and 28.3% (N = 369), respectively. In multivariate analyses, obesity was independently associated with an odds ratio (OR) = 2.21 of high-risk PCa (95% CI: 1.28-3.81), while DM was associated with an OR = 1.49 (95% CI: 1.05-2.11) of intermediate-risk PCa. Compared to non-obese men without diabetes, men with BMI = 30 and DM had increased risks of both intermediate (OR = 1.93; 95% CI 1.12-3.43) and high-risk PCa (OR = 2.40; 95% CI 1.22-4.73). Interestingly, most of the association of highrisk PCa was driven by obesity. Conclusion: In this multiethnic population both obesity and DM were independently associated with intermediate- and high-risk PCa; however, most of the association for high-risk cancer was driven by obesity. Our results corroborate findings that obesity increases the risk of aggressive PCa; however, results regarding DM need to be confirmed in other large multiethnic populations. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) infects a wide range of human cells, resulting in both benign and malignant tumors. In the last few decades, proteins and/or nucleic acids of the virus were found to be often highly expressed in in patients with basal cell hyperplasia and prostatic neoplasia. This research aimed to unravel the rate of HCMV infections among prostatic tissue subsets from Iraqi patients with adenocarcinoma and benign hyperplasia. One hundred, formalin-fixed and paraffin embedded prostatic tissues were obtained from 40 tissue samples collected from different grades of prostate carcinoma; 40 from benign prostatic hyperplasia and 20 from apparently healthy prostatic tissues. These tissue specimens were collected from the archives of different public and private histopathological laboratories in Baghdad. Detection of HCMV-DNA was achieved by a highly sensitive version of chromogenic in situ hybridization technique. The signals of chromogenic in situ hybridization reactions for HCMV-DNA detection in prostatic adenocarcinoma tissues were found in 65% (26 out of 40) of the tissues, whereas in BPH (Benign Prostatic Hyperplasia), HCMV-DNA was detected in 57.5% (23 out of 40) of the tissues, and in the healthy control group in 25% (5 out of 20) of the tissues. The highest percentage of positive- HCMV- DNACISH reactions (57.5%) was found in prostatic adenocarcinomatous tissues that showed poor differentiation. Our results could show that HCMV might contribute to the development of the studied subsets of prostatic adenocarcinoma and benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA. [ABSTRACT FROM AUTHOR]

Diabetic men have decreased risk for prostate cancer (PCa) overall and lower PSA compared to non-diabetics. This may affect the outcomes of PSA-based screening. We investigated the effect of PSA-based screening at 4-year intervals on PCa incidence and mortality separately among users and non-users of antidiabetic medication with the hypothesis that screening would detect less low-grade cancer and more high-grade cancer in diabetic men. A cohort of 80,458 men from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to national prescription database to obtain information on antidiabetic medication purchases. PCa risk and mortality were compared between the FinRSPC screening arm (SA) and the control arm (CA) separately among users and non-users of antidiabetic medication. Among antidiabetic medication users median PSA was lower than in non-users (0.93 and 1.09 ng/ml, respectively, P for difference = 0.001). Screening increased overall PCa incidence compared to CA after the first screen both among medication users and non-users (HR 1.31, 95% CI 1.08–1.60 and HR 1.55, 95% CI 1.44–1.66, respectively). On the second and third screen the difference between SA and CA attenuated only among medication users. Detection of Gleason 6 tumors was lower among medication users, whereas no difference was observed in detection of Gleason 8–10 cancers. Concordantly, screening affected PCa mortality similarly regardless of antidiabetic medication use (HR 0.38, 95% CI 0.14–1.07 and HR 0.19, 95% CI 0.11–0.33 among users and non-users after three screens, respectively. P for difference = 0.18). Median PSA is lower in men using antidiabetic drugs than among non-users. Systematic PSA screening detects less low-risk tumors among medication users, whereas detection of high-risk tumors and mortality effects are similar regardless of medication use. This suggests that antidiabetic medication users may form a suitable target group for PCa screening, with less screening-related overdiagnosis of indolent tumors. [ABSTRACT FROM AUTHOR]

To analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn't need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98–1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95–0.99, cross-sectional study OR 1.19, 95%CI 1.13–1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00–1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93–0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94–1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis. [ABSTRACT FROM AUTHOR]

The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA > 15 (77%) and/or Gleason 7 (4 + 3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug. [ABSTRACT FROM AUTHOR]

Background: The prostate cancer remains one of the most widespread and least understood of all human malignancies. Pathologic evidence suggests that neoplastic changes of the prostate epithelium begin early in man's adult life, but do not become clinically evident or relevant until decades later. The lifetime risk of a man diagnosed with PC is estimated to be 1 in 9. Global cancer incidence shows that the PC become the fifth most common cancer in the world and second most common cancer in men. Thus, better understanding of its risk factors, will eventually lead to improve the control measures and more safe health outcomes. This study aimed to investigate the impact of different medical characteristics and some behavioral factors on the development of PC in men. Results: The bivariate analysis of study revealed that age of > 55 years and positive family history were found to increase the risk of developing prostate cancer by more than two and three times (OR= 2.28, and 3.05) respectively (P<0.05). Furthermore, the active smoking, alcohol consumption and obesity (BMI of >30) were also notable as potential risk factors associated with increased risk of developing prostate cancer by 8.01, 3.79 and 5.26 times respectively (P< 0.05). The study showed that a negative association between exercise and prostate cancer (0R=043). No significant associations were found between psychological upset, dietary habits and prostate cancer (P>0.05). Conclusion: Age of 55+ years, positive family history, active smoking, alcohol consumption and obesity all appeared to be a potential risk factors for development of prostate cancer. In contrast, regular exercise, found to be significant protective factor against development of such a disease. [ABSTRACT FROM AUTHOR]

We had six cases of patients who were treated with long-term testosterone replacement therapy (TRT) after high dose-rate (HDR) brachytherapy and androgen deprivation therapy for high-risk prostate cancer. All patients were given testosterone enanthate by intramuscular injection every 3 to 4 weeks. Blood biochemistry including prostate specific antigen (PSA) level was evaluated every 3 to 6 months after TRT, and radiological imaging was performed every 12 months. All patients had slight increases in PSA within the normal range and not indicative of biochemical recurrence. A sudden increase in PSA was observed in one patient, but it finally decreased. Aging male symptoms scale and various metabolic factors were improved by TRT in all of cases. Although adverse events included polycythemia in one patient, no patients experienced disease recurrence or progression during TRT. Our results suggest TRT for high risk-patients with HDR brachytherapy for prostate cancer may be beneficial and safe. [ABSTRACT FROM AUTHOR]

Background: Studies have suggested that rapid age‐related declines of testosterone (T) level may play a critical role in the development of prostate cancer (PCa), and family history of PCa is another well‐established risk factor of PCa, which have been reported to be associated with androgen metabolism‐related genes. However, few studies have ever investigated whether a family history of PCa influences the risk of PCa via regulating the age‐related trend of T level among males over the life course. Objectives: To examine the association between family history of PCa and age‐related trend of T levels. Materials and Methods: We used National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2004 (n = 322) to compare the age‐specific T levels in males with a family history of PCa and those without. Results: We found that between two younger age groups (ages 20–39 and 40–59), there was a more pronounced drop‐off in T levels among men with a family history of PCa compared to men without a family history. Discussion and Conclusion: This preliminary analysis suggested that men with a family history of PCa may experience a sharper decline in T level over the life course as compared to males without a family history. However, no conclusions can be made due to small sample sizes. Further longitudinal studies with large sample sizes are needed. [ABSTRACT FROM AUTHOR]

Introduction: Previous Canadian epidemiologic studies have identified associations between occupations and prostate cancer risk, though evidence is limited. However, there are no well-established preventable risk factors for prostate cancer, which warrants the need for further investigation into occupational factors to strengthen existing evidence. This study uses occupation and prostate cancer information from a large surveillance cohort in Ontario that linked workers' compensation claim data to administrative health databases. Methods: Occupations were examined using the Occupational Disease Surveillance System (ODSS). ODSS included 1 231 177 male workers for the 1983 to 2015 period, whose records were linked to the Ontario Cancer Registry (OCR) in order to identify and follow up on prostate cancer diagnoses. Cox proportional hazard models were used to calculate age-adjusted hazard ratios and 95% CI to estimate the risk of prostate cancer by occupation group. Results: A total of 34 997 prostate cancer cases were diagnosed among workers in ODSS. Overall, elevated prostate cancer risk was observed for men employed in management/administration (HR 2.17, 95% CI = 1.98-2.38), teaching (HR 1.99, 95% CI = 1.79-2.21), transportation (HR 1.20, 95% CI = 1.16-1.24), construction (HR 1.09, 95% CI = 1.06-1.12), firefighting (HR 1.62, 95% CI = 1.47-1.78), and police work (HR 1.20, 95% CI = 1.10-1.32). Inconsistent findings were observed for clerical and farming occupations. Conclusion: Associations observed in white collar, construction, transportation, and protective services occupations were consistent with previous Canadian studies. Findings emphasize the need to assess job-specific exposures, sedentary behaviour, psychological stress, and shift work. Understanding specific occupational risk factors can lead to better understanding of prostate cancer etiology and improve prevention strategies. [ABSTRACT FROM AUTHOR]

In this gendered autoethnography, I critically analyze my personal thoughts on how my Christian faith informs my advocacy-oriented practice for African American men at risk for prostate cancer in Louisiana. This autoethnographic narrative will utilize the theoretical framework of Critical Race Theory (CRT) and intersectionality to explore the author's lived experience as a researcher-practitioner problematizing the intersection of race and racism, health, and faith among African American men over the age of 50 at risk for prostate cancer. A review of the literature suggests research that examines the experiences and intersectional identities of Louisiana Black men at risk for prostate cancer is limited. By inquiring through an autoethnographic approach, Christian social work practitioners can become more aware of oppressive policies and practices in contemporary American society which negatively African American men at risk for prostate cancer in Louisiana. [ABSTRACT FROM AUTHOR]

Background: Disrupted sleep rhythms may lead to cancer development. We conducted a population-based cohort study to evaluate the incidence and risk of prostate cancer in patients with sleep disorders (SDs).Methods: Patients newly diagnosed with SDs between 2000 and 2010 were enrolled from the Taiwan Longitudinal Health Insurance Database. A non-SD cohort age-matched (5-y intervals), comorbidities, and medications was randomly sampled from the general population at a 1:1 ratio. The follow-up period extended from the index date of SDs to the diagnosis of prostate cancer, censoring, or the end of 2013. We used Cox proportional hazards models to calculate the risk of prostate cancer.Results: In total, 41,444 patients were enrolled in each cohort. The mean age of the SD cohort was 48.0 years and that of the non-SD cohort was 47.8 years, with 58.2% of both cohorts aged younger than 50 years. The incidence of prostate cancer increased with age. The overall incidence of prostate cancer was higher in the SD cohort than in the non-SD cohort (9.56 vs 6.36 per 10,000 person-y), with an adjusted hazard ratio of 1.42 (95% CI = 1.20-1.69). Age-specific analysis revealed a 1.35-fold increased risk of prostate cancer in the patients aged ≥65 years in the SD cohort compared with the non-SD counterparts (95% CI = 1.10-1.65).Conclusions: Patients with SDs are associated with increased risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Alkylphenolic compounds are chemicals with endocrine disrupting properties that have been widely used in industry with important changes in their usage over time. Few epidemiologic studies have evaluated the effect of alkylphenolic compounds on human health. Objectives We investigated whether occupational exposure to alkylphenolic compounds is associated with breast and prostate cancer. Methods We carried out a population-based case–control study including 1513 incident cases of breast cancer, 1095 of prostate cancer, and 3055 controls, frequency matched by sex, age and region. Occupational exposure to alkylphenolic compounds was estimated using a recently developed job-exposure matrix, which considered different scenarios of exposure and different subtypes of alkylphenolic compounds. Results History of occupational exposure to alkylphenolic compounds was modestly associated with breast cancer (OR = 1.23; 95% CI = 1.01–1.48). Within the different scenarios, the occupational use of domestic tensioactives was positively associated with breast cancer (OR = 1.28; 95% CI = 1.02–1.60), while occupational exposure in other scenarios showed mostly a suggestion of a similar positive associations. Exposure to nonylphenol ethoxylates was positively associated with breast cancer (OR = 1.21; 95% CI = 1.00–1.47), while exposure to other compounds was uncommon. In general, we did not observe associations between alkylphenolic compounds and prostate cancer, except for a positive association among men occupationally exposed to cosmetic, hair and personal hygiene products. Conclusions Our findings suggest a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds, and no associations between these compounds and prostate cancer risk. These findings warrant further corroboration in other studies. Highlights • This is the largest study examining occupational exposure to alkylphenolic compounds and breast and prostate cancer risk. • We observed a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds. • Our findings suggest no significant associations for prostate cancer and these compounds. • Among women, nonylphenol ethoxylates were the most frequent compound, which was positively associated to breast cancer. • The elucidation of the role of these compounds should shed a light on the etiology of those diseases and help informing public health decisions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to examine the relationship between proinflammatory diet and prostate cancer risk.Methods: Energy-adjusted Dietary Inflammatory Index (E-DII) scores were computed among 40,161 participants in the California Men's Health Study. Over 9.7 ± 3.8 years of follow-up, 2707 incident prostate cancer cases were diagnosed and categorized as low-, intermediate-, or high-risk, based on disease grade and stage. Accelerated failure-time models assessed time to diagnosis of prostate cancer. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (95% CI). Nonlinear effects of E-DII were modeled as third-order polynomials.Results: Time to prostate cancer diagnosis did not differ by E-DII quartile. The HR for high-risk prostate cancer increased in the third E-DII quartile (HRQ3 vs. Q1 = 1.36; 95% CI: 1.04-1.76), but not in the fourth (HRQ4 vs. Q1 = 0.99; 95% CI: 0.74-1.32, Ptrend = .74), suggesting a nonlinear dose-response. HR curves for prostate cancer increased exponentially above an E-DII threshold of ≈+3.0. HR curves for high-risk prostate cancer had a much steeper incline above an E-DII threshold of ≈+2.5. Curves were higher among Blacks and Whites relative to other races and among overweight or obese men. No relationship was observed between E-DII scores and intermediate- or low-risk disease.Conclusions: Relationships between proinflammatory diet and prostate cancer risk may be nonlinear, with an increased risk above an E-DII threshold of ≈+2.5. [ABSTRACT FROM AUTHOR]

Abstract Malfunction of apoptosis plays a key role in carcinogenesis. Previous studies have reported that polymorphisms in caspase genes could lead to poor apoptotic signaling, thus facilitating the onset of several human cancers. The aim of this study was to evaluate the association between three polymorphisms (rs1049216, rs2705897 and rs4647603) of the CASP3 gene and the risk of prostate cancer (PCa) in Galicia (NW Spain).The relationship between these single nucleotide polymorphisms (SNPs) and PCa in European populations has yet to be studied. To test this hypothesis, we carried out a case-control study on a total of 243 patients with PCa and 191 healthy individuals, genotyping all polymorphisms using the matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) method. Overall, none of the polymorphisms were clearly associated with the risk of PCa. Nevertheless, the results drawn from this study suggest that genetic variability in the CASP3 gene, in combination with lifestyle and environmental factors may influence the predisposition to develop PCa in the Galician population. Specifically, the results of study seem to hint at a higher risk of PCa in smokers of up to 20 pack-years (PY) and carriers of both the CASP3 -rs1049216 GG genotype and the G allele (OR = 3.61, p = 0.044; OR = 1.71; p = 0.018). In addition, the GG and AG genotypes showed increased predisposition to PCa in overweight individuals (OR = 4.43, p = 0.040; OR = 2.00; p = 0.022). Finally, the CASP3- rs4647603 CT genotype and T allele were associated with a higher susceptibility to PCa in obese individuals (OR CT/TT = 4.30, p = 0.003; OR T/C = 3.58, p = 0.004). Further replication studies in other populations are required to assess these findings. Highlights • We investigate the association between polymorphisms in CASP3 and prostate cancer. • GG genotype (rs1049216) elevates the risk of PCa in smokers (<20PY) individuals. • GG/AG genotypes (rs1049216) in overweight subjects exhibit an increased risk to PCa. • T allele (rs4647603) shows a greater susceptibility to PCa in obese persons. [ABSTRACT FROM AUTHOR]

Introduction: The question of whether pioglitazone, an antidiabetic drug, increases the risk of cancer has been debated for some time. Recent studies have shown that pioglitazone use can increase the risk of prostate cancer as well as pancreatic cancer. However, it is unclear whether pioglitazone is a causal risk factor for these cancers.Methods: In this study, we aimed to explore the direct targets of pioglitazone and genes associated with this drug by querying open platforms in order to construct a biological function network, and then to further evaluate the relationships of pioglitazone with prostate cancer and pancreatic cancer.Results: We first tested our hypothesis using DrugBank and STRING. We identified four direct targets of pioglitazone and 50 pioglitazone-associated genes, which were then selected for KEGG pathway analysis using STRING and WebGestalt. This analysis generated the top 25 KEGG pathways, among which four pathways were related to site-specific cancers, including prostate cancer and pancreatic cancer. Finally, a genomic study using cBioPortal indicated that genomic alterations of two gene sets related to the prostate cancer and pancreatic cancer pathways, respectively, are associated with the acceleration of carcinogenesis.Conclusions: Pioglitazone is likely to be a causal risk factor for prostate cancer and pancreatic cancer, so this drug should be used with caution. The present research also demonstrates the use of biological function network analysis to effectively explore drug interactions and drug safety profiles. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies regarding the relationship between acne and prostate cancer risk have reported inconsistent results. We performed the present meta-analysis of observational studies to summarize the evidence on this association. Methods: A comprehensive literature search up to March 2018 was performed in PubMed, Scopus, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were estimated with a random effects model. The Q statistic and the I2 index were used to evaluate the heterogeneity across the studies. Results: Eight studies were ultimately included in this meta-analysis. In the overall analysis, no significant association was found between acne and prostate cancer risk (OR = 1.08, 95% CI 0.93–1.25). A significant heterogeneity was observed across studies (P = 0.006, I2 = 64.5%). In the subgroup analysis by study design, a significant association was observed in the cohort studies (OR = 1.51, 95% CI 1.19–1.93) but not in the case-control studies (OR = 0.98, 95% CI 0.86–1.12). Conclusions: In summary, this meta-analysis did not find an association between acne in adolescence and prostate cancer risk. However, because there was some heterogeneity in the overall analysis and a significant association was observed in the meta-analysis of the cohort studies, further well-designed large prospective studies are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Abstract Purpose The available data demonstrating that superiority of LDR brachytherapy (LDR-BT) boost in high-risk prostate cancer patients under represents patients with extracapsular extension (T3a) and/or seminal vesicle invasion (T3b) have been limited. We report long-term clinical outcomes data for patients with cT3a/b disease receiving LDR-BT. Methods and Materials Ninety-nine men (median age: 69.4 years) with cT3a/bN0M0 high-risk prostate adenocarcinoma received definitive LDR-BT or LDR-BT boost after external beam radiation therapy (EBRT) at a single institution between 1998 and 2007. About 86% of patients received androgen deprivation therapy. Freedom from biochemical failure (FFBF), prostate cancer–specific survival (PCSS), and overall survival (OS) was calculated using the Kaplan–Meier method with the Phoenix definition used as definition of failure. Cox regression analysis was used to compare outcomes between clinical stage, initial PSA, Gleason Score, and percent core positive rate. Results With a median followup of 7 years, 7-year rate of FFBF, PCSS, and OS for the entire cohort was 65.2% (±5.6%), 90.1% (±3.6%), and 77.9% (±4.7%), respectively. LDR-BT boost patients achieved a 7-year FFBF rate of 73.5 (±6.5%). No significant difference in outcomes was present between T3a or T3b disease, Gleason score, iPSA stratification and percent core positive rates. Conclusions LDR-BT, primarily as a boost in conjunction with ADT and EBRT, is not only feasible, but also highly effective in men with cT3a and cT3b high-risk prostate cancer resulting in excellent biochemical control and survival outcomes. LDR-BT boost implantation of patients should be strongly considered for cT3 patients given the merits of trimodality care. [ABSTRACT FROM AUTHOR]

Abstract Purpose Although external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) offers a 20% improvement in biochemical progression-free survival compared with dose-escalated EBRT alone for men with intermediate and high-risk prostate cancer, population studies show a concerning decline in BB utilization. Methods We modified our clinical pathway (CP) in January 2016 to indicate EBRT with BB as first-choice modality for high-risk prostate cancer, based on preliminary findings of Androgen Suppression Combined with Elective Nodal and Dose-Escalated Radiation Therapy. A retrospective review was performed on 659 patients with high-risk prostate cancer treated with definitive intent EBRT ± BB within a network of 19 sites between December 2011 and July 2017. χ 2 test was used to determine changes in practice pattern before vs. after CP modification. Results Before CP modification, 25.2% of patients were planned for BB, compared with 45.4% afterward (p < 0.001). Among 23 nonbrachytherapist physicians, utilization of BB increased from 3.4% to 14.8% (p < 0.001) after CP modification. Among nine brachytherapists, utilization increased from 46.4% to 55.6% (p = 0.120). Among patients treated by a nonbrachytherapist who did not receive BB, the reason was physician preference in 59.7%, patient preference in 19.9%, and other in 20.4%. Conclusion Based on recent evidence suggesting improved biochemical progression-free survival with use of BB for high-risk prostate cancer, we modified our CP, after which we observed increased use of a BB across a network, especially among physicians who do not perform brachytherapy. However, physician preference remains the most significant factor in the nonutilization of BB. New mechanisms are needed to overcome this barrier. [ABSTRACT FROM AUTHOR]

Abstract Background Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. Objective To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. Design, setting, and participants Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. Outcome measurements and statistical analysis Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. Results and limitations Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR = 0.77, 95% confidence interval [CI] 0.69–0.86; p < 0.001) compared with men with higher concentrations (2nd–10th tenths of the distribution). Heterogeneity was present by tumour grade (p het = 0.01), with a lower risk of low-grade disease (OR = 0.76, 95% CI 0.67–0.88) and a nonsignificantly higher risk of high-grade disease (OR = 1.56, 95% CI 0.95–2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. Conclusions Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. Patient summary In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer. Take Home Message We found that men with low circulating free testosterone had a 23% reduced risk of overall prostate cancer, but there was some evidence that these men had an increased risk of developing high-grade disease. [ABSTRACT FROM AUTHOR]

Abstract Background The fecal microbiome is associated with prostate cancer risk factors (obesity, inflammation) and can metabolize and produce various products that may influence cancer but have yet to be defined in prostate cancer. Objective To investigate gut bacterial diversity, identify specific metabolic pathways associated with disease, and develop a microbiome risk profile for prostate cancer. Design, setting, and participants After prospective collection of 133 rectal swab samples 2 wk before the transrectal prostate biopsy, we perform 16S rRNA amplicon sequencing on 105 samples (64 with cancer, 41 without cancer). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. The p values were adjusted using the false discovery rate. The α- and β-diversity analyses were performed using QIIME. The Mann-Whitney U test was employed to evaluate the statistical significance of β-diversity distances within and between groups of interest, and least absolute shrinkage and selection operator (LASSO) regression analysis was used to determine pathway significance. Outcome measurements and statistical analysis The detection of prostate cancer on transrectal prostate needle biopsy and 16s microbiome profile. Results and limitations We identified significant associations between total community composition and cancer/non-cancer status (Bray-Curtis distance metric, p < 0.01). We identified significant differences in enrichments of Bacteroides and Streptococcus species in cancer (all p < 0.04). Folate (LDA 3.8) and arginine (LDA 4.1) were the most significantly altered pathways. We formed a novel microbiome–derived risk factor for prostate cancer based on 10 aberrant metabolic pathways (area under curve = 0.64, p = 0.02). Conclusions Microbiome analyses on men undergoing prostate biopsy noted mostly similar bacterial species diversity among men diagnosed with and without prostate cancer. The microbiome may have subtle influences on prostate cancer but are likely patient-specific and would require paired analysis and precise manipulation, such as improvement of natural bacterial folate production. Patient summary Microbiome evaluation may provide patients with personalized data regarding the presence or absence of particular bacteria that have metabolic functions and implications regarding prostate cancer risk. The study provides a basis to investigate the manipulation of aberrant microbiomes to reduce prostate cancer risk. Take Home Message We note minimal differences in the microbiome profiles between men diagnosed with and without prostate cancer. While a global microbiome profile is unlikely to predict prostate cancer, bacteria associated with a specific metabolic pathway, such as B vitamins, do seem to have an association with prostate cancer and warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract Prostate cancer is one of the leading causes of cancer-related mortality among men living in developed countries, making the development of safe, practical approaches to prostate cancer risk reduction a high research priority. The relationship between prostate cancer risk and selenium, an essential nutrient required for a number of metabolically important enzymes including glutathione peroxidases, has been investigated, but a satisfactory integration of results has proven elusive. Dogs, like men, naturally develop prostate cancer during aging, providing an appropriate context to study the effects of selenium supplementation on the dysregulation of homeostasis that drives cancer development within the aging prostate. In this paper, we summarize the translational significance of research results gained from dog studies on selenium and prostate cancer risk. Our discovery of a U-shaped dose-response between toenail selenium concentration and prostatic DNA damage in dogs remarkably parallels data on the relationship between selenium status and prostate cancer risk in men. Notably, the dog U-curve provides a plausible explanation for the unanticipated increase in prostate cancer incidence among men with highest baseline selenium who received selenium supplementation in the largest-ever prostate cancer prevention trial (SELECT). Moreover, the dog U-curve guided the discovery of a non-antioxidant, anti-carcinogenic mechanism of organic selenium — the preferential triggering of apoptosis in DNA damaged cells, which we have termed "homeostatic housecleaning". Taken together, the data from dogs and men indicate that increasing selenium status will not necessarily be associated with prostate cancer risk reduction. Landing in the trough of the U — achieving mid-range selenium status — is better than being too low or too high. Personalizing health promotion in a more-is-not-necessarily-better world poses distinctive challenges. Dog studies can be relied upon to contribute important insights into dose-dependent and form-dependent effects — two critical aspects of selenium biology that will have to be disentangled if the burgeoning science of selenium is to be translated into effective strategies for human disease prevention. Beyond contributing to understanding the role of selenium in biology, our work situates the concept of U-shaped thinking at the core of personalized medicine and precision nutrition. Graphical abstract fx1 Highlights • A U-shaped dose response informs more selenium is not always better for risk reduction. • Dog studies can integrate results of human studies and guide discovery of mechanisms. • A dog U-curve provides a map for interpreting the results of men studied in SELECT. • The critical hypothesis regarding selenium and prostate cancer risk remains untested. • U-shaped thinking is an essential element of personalized (precision) medicine. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to evaluate the diagnostic performance of 3.0-T multiparametric magnetic resonance imaging (mpMRI) in preoperative staging of prostate cancer (PCa) and its influence on the extent of resection during endoscopic radical prostatectomy (ERP) among cancer risk groups.Material and Methods: The data of 154 patients with PCa in whom mpMRI was performed prior to ERP between 2011 and 2015 were included. The initial decision whether to perform neurovascular bundle (NVB) sparing surgery was based on EAU guidelines. mpMRI images were reevaluated prior to prostatectomy to modify the surgical template. Imaging was compared with pathological reports to investigate the diagnostic performance of mpMRI.Results: The surgical template was modified in 69 (44.8%) patients after reevaluation of mpMRI. More preserving NVB sparing was attempted in 17 (11.0%) men, in whom NVB would have been resected if mpMRI had not been available. More aggressive NVB resection was performed in 52 (33.8%) men, in whom innervation would have been spared if basing solely based on guidelines. Among all PCa risk groups mpMRI had an impact on the surgical template with more aggressive surgery in 63.0% and 33.3% of men in the low- and intermediate-risk group, respectively, and more preserving in 21.4% of the high-risk patients. The change in extent of resection was not correlated with a higher risk of positive surgical margins (p = 0.196).Conclusions: Preoperative mpMRI exerts a significant impact on decision making concerning the extent of resection during ERP irrespective of the PCa risk group. [ABSTRACT FROM AUTHOR]

Background: Androgenetic alopecia (AGA) seems to be a marker of increased risk of prostate cancer (PCa). Objective: We sought to investigate potential pathophysiological differences between frontal and vertex balding that might have the impact on the incidence of PCa. Methods: Serum concentrations of testosterone (T), dihydrotestosterone (DHT) and prostate‐specific antigen (PSA) were measured in 88 subjects with AGA. Results: We have examined sixty patients with frontal baldness and 28 patients with vertex baldness. The subgroups did not differ significantly in age, BMI and as regards age of AGA onset, duration of AGA and comorbidities. The mean value of DHT in serum of the men with vertex baldness was higher than those in the men with frontal baldness with statistical significance (P < 0.05). The groups did not show significant differences in mean value of serum T and PSA levels, and DHT/T ratio. No correlation was found between the serum PSA level and serum androgen levels as well as DHT/T ratio. Conclusions: Vertex baldness may signal higher exposures to circulating DHT. Serum PSA level cannot serve as surrogate diagnostic marker of increased androgenic activity in men with AGA. [ABSTRACT FROM AUTHOR]

Introduction: Environmental and occupational human exposure from neutron source can lead to the serious biologic effects. The aim of this study is to evaluate the cancer incidence risk for various human organs at different neutron dose levels due to exposure from an Americium-241/Beryllium (Am-241/Be), a standard neutron source for calibration purposes. Material and Methods: We measured ambient dose equivalent H*(10) at different distances from Am-241/Be mixed neutron source by Berthold LB 6411 detector and determined cancer incidence risk for different organs of both male and female subjects at different neutron exposure levels by BEIR VII model. Results: Exposure age had a reverse impact on cancer incidence risk of different organs. We found that as H*(10) increases, cancer incidence risk increments as well. Colon (for men) and bladder (for women) had the highest sensitivity to neutron exposure, while prostate and uterus showed the lowest risk of cancer incidence among male and female subjects, respectively. Conclusion: Older exposed persons are at a lower risk of cancer incidence. The risk of cancer incidence for various organs is considerably associated with gender, such that radiation sensitivity of female organs was higher at all the measured neutron dose levels. [ABSTRACT FROM AUTHOR]

Background: Dynamic longitudinal patterns in body mass index (BMI) have been suggested to better predict health outcomes than static measures. Effects of BMI trajectories on prostate cancer (PCa) risk have not been thoroughly explored. Methods: Cohort data were derived from electronic medical records of patients who were admitted to a tertiary‐care hospital in the Southeastern USA during 1994‐2016. Patients with a history of urologic clinic visit because of any prostatic condition and with repeatedly measured BMI (n = 4857) were included. BMI trajectories prior to PCa diagnosis were assessed using the developmental trajectory analysis method. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) for overall and grade‐specific PCa. Results: The median age (interquartile range, IQR) of the participants at baseline was 63 (54, 72) years. Over a median follow‐up (IQR) of 8.0 (2.0, 13.0) years, 714 (14.7%, 714/4857) were diagnosed with PCa. Men with growing BMI trajectory progressing from normal weight to overweight/obese had a 76% increased PCa risk (aHR = 1.76; 95% CI: 1.25, 2.48), and men being obese and experiencing progressive weight gain had 3.72‐fold increased PCa risk (aHR = 3.72; 95% CI: 1.60, 8.66), compared to men with persistently normal BMI. The associations were more pronounced for PCa with Gleason score ≥7. No significant association of decreasing BMI trajectory progressing from obese to normal BMI was found with PCa risk. Conclusions: Progressively body weight gain during middle‐to‐late adulthood was associated with increased PCa risk for both normal weight and overweight men. Further studies are warranted to confirm this finding. Growing BMI trajectories in middle‐to‐late adulthood were related to increased prostate cancer risk, particularly for high‐grade prostate cancer. [ABSTRACT FROM AUTHOR]

The objective of this work was to investigate the clinical significance of promoter gene DNA methylation changes in whole blood from African-American (AA) men with prostate cancer (PCa). We used high throughput pyrosequencing analysis to quantify percentage DNA methylation levels in a panel of 8 genes (RARβ2, TIMP3, SPARC, CDH13, HIN1, LINE1, CYB5R2 and DRD2) in blood DNA obtained from PCa and non-cancerous controls cases. Correlations of methylation status and various clinicopathological features were evaluated. Six genes tested achieved significant difference in DNA methylation levels between the PCa compared to control cases (P < 0.05). The TIMP3 loci demonstrated significant correlation of DNA methylation with age for all cases analyzed (p < 0.05). We observed an inverse correlation between CDH13 methylation (p = 0.045; r = -0.21) and serum vitamin D level whereas TIMP3 methylation (p = 0.021; r = -0.24) and DRD2 methylation (p = 0.056; r = -0.201) showed inverse correlation with supplementary vitamin D in the cancer cases. We also observed a direct correlation between methylation of RARβ2 (p = 0.0036; r = 0.293) and SPARC (p = 0.0134; r = 0.20) loci with PSA level in the controls but not the cancer cases. In addition, alcohol cases significantly correlated with higher RARβ2 methylation (p = 0.0314) in comparison with non-alcohol cases. Furthermore, we observed an inverse correlation of DRD2 methylation (p = 0.0349; r = -0.343) and Gleason score. Our data suggests that promoter methylation occurred more frequently in the blood of AA PCa and is associated with various clinicopathological features in AA men with PCa. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) are at a higher risk of many types of cancer. However, specific investigation of the risk of prostate cancer and the influence of COPD pharmacotherapy in patients with COPD is lacking. This study investigated the risk and influence of COPD pharmacotherapy on risk of prostate cancer in patients with COPD. Methods: This retrospective cohort study used data from Taiwan’s Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort comprised COPD patients who received treatment between 2004 and 2008, and who were identified from the LHID2005. The control cohort comprised patients without COPD and was matched to the study cohort by age and sex. Two-stage propensity score calibration with the National Health Interview Survey 2005 was performed to obtain the missing confounders of smoking, alcohol drinking, and body mass index in the LHID. The hazard ratio (HR) and adjusted HR were estimated. Moreover, the influence of inhaled medications and other related medication on the risk of prostate cancer was analyzed by Cox proportional hazard regression. Results: The COPD cohort comprised 12,774 patients, and the control cohort comprised 38,322 patients (1:3). The incidence of prostate cancer was 633 per 100,000 person-years in the COPD cohort and 361 per 100,000 person-years in the control cohort. The propensity score calibration-adjusted HR was 1.62 (95% CI, 1.40–1.87, p < 0.001) in the COPD cohort. Further analysis revealed that the adjusted HR for the risk of prostate cancer was 1.61 (95% CI, 1.19–2.16, p = 0.002) in patients with COPD who used short-acting muscarinic antagonists (SAMAs) and 1.89 (95% CI, 1.40–2.54, p < 0.001) in patients with COPD who used short-acting beta-agonists (SABAs). COPD patients had lower risk of prostate cancer when using statin (HR = 0.63, 95% CI, 0.45–0.89, p = 0.010) or aspirin (HR = 0.55, 95% CI, 0.35–0.85, p = 0.008). Conclusion: Patients with COPD are at a higher risk of prostate cancer, particularly those using SAMAs or SABAs. This finding suggests that inflammation control may be an effective strategy for decreasing the risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract Introduction The role of sexual activity (SA) on prostate cancer (PCa) risk is still controversial. Aim To determine the associations among number of female sexual partners, age at first intercourse, ejaculation frequency (EF), and the risk of PCa. Methods A systematic literature search on MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted to identify the relevant studies published before April 2018. We calculated the summary odds ratio (OR) and 95% CI to determine the association between SA and PCa risk. A 2-stage dose-response meta-analysis was performed to explore the trend from the correlated log OR estimates. Main Outcome Measures Outcome measures included characteristics of included studies, associations among number of female sexual partners, age at first intercourse, as well as EF and PCa risk. Results A total of 21 case-control studies and 1 cohort study with 55,490 participants (14,976 patients and 40,514 controls) were included in this meta-analysis. Linear and significant dose–response associations were found among number of female sexual partner as well as age at first intercourse and PCa risk, an increment of 10 female sexual partners associated with a 1.10-fold increase of PCa risk (OR 1.10, 95% CI 1.01–1.21), and the risk of PCa was decreased by 4% for every 5-year delay in age at first intercourse (OR 0.96, 95% CI 0.92–0.99). Although no linear association was observed between EF and the risk of PCa, moderate EF (2–4 times per week) was significantly associated with a lower risk of PCa (OR 0.91, 95% CI 0.87–0.96). Clinical Implications Modification of SA factors would appear to be a useful low-risk approach to decreasing the risk of PCa. Strengths & Limitations This is the first dose–response meta-analysis performed to describe the association between SA and PCa risk. However, the direction of causality between SA and risk of PCa should be interpreted with caution because most included studies used case-control design. Conclusion Meta-analysis of the included studies indicated that men with fewer sexual partner numbers, older age at first intercourse, and moderate frequent ejaculation were associated with a significantly decreased risk of PCa. Jian Z, Ye D, Chen Y, et al. Sexual Activity and Risk of Prostate Cancer: A Dose–Response Meta-Analysis. J Sex Med 2018;15:1300–1309. [ABSTRACT FROM AUTHOR]

Background. Prostate cancer (PCa) is the first in terms of occurrence in Europe and second in Poland. The PCa risk factors include: genetic load, obesity, diet rich in fat, hypertriglyceridemia, and exposure to androgens. The prostate-specific antigen (PSA) level may be elevated in prostate cancer or other prostate disorders. Fat tissue secretes adipocytokines, which increase the risk of cancer development and metastasis. Objectives. The aims of the study were to investigate the relationship between circulating levels of PSA, adipocytokines: omentin, leptin, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in serum obtained from patients with benign prostate hyperplasia (BPH) and prostate cancer (PCa). Methods. Forty patients diagnosed with BPH and forty diagnosed with PCa were assessed for the purpose of the study. The concentrations of omentin, leptin, HGF, and VEGF were determined using enzyme-linked immunosorbent assays (EIA). Results. PSA level was significantly higher in the PCa group than in BPH (18.2 versus 9 ng/mL, p<0.01), while volume of prostate gland was significantly higher in the BPH group than in PCa (39.1 versus 31.1 cm3, p=0.02). HGF, VEGF, omentin, and leptin concentrations were significantly higher in PCa group than in BPH (359.5 versus 294.9 pg/mL, p=0.04; 179.3 versus 127.3 pg/mL, p<0.01; 478.8 versus 408.3 ng/mL, p=0.01; 15.7 versus 11.2 ng/mL, p=0.02, resp.). The multiple logistic regression analysis demonstrated that only omentin and PSA levels were independent predictors of PCa in studied subjects. Conclusions. PSA level as well as the level of omentin may be valuable markers of PCa with clinical significance, when compared to PSA. [ABSTRACT FROM AUTHOR]

Introduction: Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. Methods: We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype—cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. Results: The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. Conclusions: Phototype is not associated with breast or prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the performance of mpMRI and the 4Kscore test together for the detection of significant prostate cancer. Material and methods We selected a consecutive series of men who were referred for evaluation of prostate cancer at an academic institution and underwent mpMRI and the 4Kscore test. The primary outcome was the presence of Gleason 7 or higher cancer on biopsy of the prostate. We used logistic regression and Decision Curve Analysis to report the discrimination and clinical utility of using mpMRI and the 4Kscore test for prostate cancer detection. We modeled the probability of harboring a Gleason 7 or higher prostate cancer based on the 4Kscore test and mpMRI findings. Finally, we examined various combinations and sequences of mpMRI and the 4Kscore test and assessed the impact on biopsies avoided and cancers missed. Results: Among 300 men who underwent a 4Kscore test and mpMRI, 149 (49%) underwent a biopsy. Among those, 73 (49%) had cancer, and 49 (33%) had Gleason 7 cancer. The area under the curve (AUC) for using the 4Kscore test and mpMRI together 0.82 (0.75–0.89) was superior to using the 4Kscore 0.70 (0.62–0.79) or mpMRI 0.74 (0.66–0.81) individually (p = 0.001). Similarly, decision analysis revealed the highest net benefit was achieved using both tests. Conclusions: The 4Kscore test and mpMRI results provide independent, but complementary, information that enhances the prediction of higher-grade prostate cancer and improves patient’s selection for a prostate biopsy. Prospective trials are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between the use and results of early confirmatory testing and persistence on active surveillance (AS).Methods: We identified all men in the Michigan Urological Surgery Improvement Collaborative registry diagnosed with favorable-risk prostate cancer from June 2016 to June 2017. We next examined trends in the use of early confirmatory test(s), defined as repeat biopsy, prostate magnetic resonance imaging, or molecular classifiers obtained within 6 months of the initial cancer diagnosis, in patients with favorable-risk prostate cancer. We then compared the proportion of men remaining on AS 6 months after diagnosis according to reassuring vs nonreassuring results, also stratifying by age and Gleason score.Results: Among 2529 patients, 32.7% underwent early confirmatory testing within 6 months of diagnosis. Its use increased from 25.4% in the second quarter of 2016 to 34.9% in the second quarter of 2017 (P = .025). Molecular classifiers were most frequently used (55%), followed by magnetic resonance imaging (34%) and repeat biopsy (11%). Sixty-four percent (n = 523) had a reassuring result. Rates of AS were higher for patients with early reassuring results; 82% remained on AS (n = 427) compared to 52% (n = 157) of those with nonreassuring results and 51% (n = 873) with no early confirmatory testing (P <.001).Conclusion: Rates of AS are higher among men with early reassuring results, supporting the clinical utility of these tests. Nonetheless, high rates of AS among patients with nonreassuring results underscore the complexity of shared decision-making in this setting. [ABSTRACT FROM AUTHOR]

Background: Currently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with high-risk PCa who are treatable by RP alone.Methods: We retrospectively reviewed data on 315 patients with D’Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors.Results: At a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92, p < 0.05) and % positive core (≥ 30%, HR 2.85, p < 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03; p < 0.0001).Conclusion: The risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%). [ABSTRACT FROM AUTHOR]

Background/Aims: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules which play a significant role in transcriptional and translational regulation. Published data on the association between the miRNA SNPs and prostate cancer (PCa) risk are somewhat inconclusive. Methods: We performed a meta-analysis of all available studies including 2,227 patients and 2,331 control subjects to evaluate the impact of three common genetic variants of microRNAs in prostate cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the strength of the association. Results: For miR-499 polymorphism, a significant association was observed between the rs3746444 A>G polymorphism and PCa risk in heterozygote comparison and dominant genetic model, in particular in Asian population subgroup. For miR-146a polymorphism, the rs2910164 CC genotype was associated with decreased PCa risk in Asian population in homozygote comparison. In addition, rs2910164 CC genotype had a weekly higher percentage value in subgroup of Gleason score < 7. Similar results were also indicated in localized prostate cancer in subgroup analysis by tumor stage. For miR-196a2 polymorphism, no association was observed between this variant and PCa risk in the overall group. However, in stratified analysis by ethnicity, we found that rs11614913 T allele was a risk factor for Asian PCa patients. Conclusions: Polymorphisms of miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 may contribute to the risk for developing prostate cancer in Asian descendants. Moreover, miR-146a rs2910164 polymorphism was related to PCa prognosis. [ABSTRACT FROM AUTHOR]

Background: Implementation of risk-based prostate cancer screening has been proposed as a means to reduce the harms of PSA screening. Little is known, however, about the factors influencing men’s decision to attend a prostate cancer screening based on a risk assessment. Method: We sent postal invitations with a login to a survey to 10.000 men, three months before invitation to a risk-based prostate cancer screening. Prostate cancer specific worry, prostate cancer-related knowledge, health behaviour, and health related quality of life were used as predictors of subsequent participation. Participation to risk-based prostate cancer screening was defined as providing a blood sample for the STHLM3 trial, a study evaluating a risk-based model that predicts the risk for aggressive prostate cancer. Results: With a response rate of 20%, 1.347 men (70%) participated in ensuing risk-based prostate cancer screening three months later whereas 568 men (30%) declined participation in the STHLM3-study. These decliners reported less worry and feeling less vulnerable to prostate cancer and responded “Do not know” more often than participants when asked questions about prostate cancer knowledge. Participants reported greater benefits of prostate testing (p = 0.0005), less barriers to prostate testing (p<0.0001), and higher intention to attend prostate cancer testing (p<0.0001) than decliners. Finally, participants reported better overall health than decliners (p<0.0001). Conclusion: Prostate cancer worry, PC knowledge, health behaviour and quality of life were identified as predictors of participation in risk-based prostate cancer screening. Targeting these predictors may improve the participation rates. These results can inform policymaking for future population-based prostate cancer screening programs that should address potential worry in men and lack of knowledge about prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the impact of repeating a prostate‐specific antigen (PSA) level assessment on prostate biopsy decision in a cohort of men undergoing prostate biopsy. Patients and Methods: From 2015 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12‐core transrectal ultrasonography‐guided prostate needle biopsy. Indication for prostate biopsy was a PSA level of ≥4 ng/mL. Demographic, clinical, and histopathological data were collected. The PSA level was tested at enrolment (PSA1) and 4 weeks later on the day before biopsy (PSA2). Variations in PSA level were defined as: stable PSA2 within a 10% variation, stable PSA2 within a 20% variation, PSA2 decreased by ≥10%, PSA2 decreased by ≥20%, PSA2 increased by ≥10%, PSA2 increased by ≥20%, and PSA2 <4 ng/mL. Percentages and multinomial logistic regression were used to analyse biopsy outcomes. High‐grade cancer was defined as Grade group ≥3. Results: Overall, 331 patients were enrolled. Prostate cancer was diagnosed in 153/331 (46%) patients and of them 80/153 (52%) had high‐grade disease. When compared to the rest of the population, patients with a stable PSA within 20% variation had a higher risk of prostate cancer (odds ratio [OR] 1.80, P < 0.05) and high grade disease (OR 2.56, P < 0.05), patients with a PSA2 decreased by ≥20% had a lower risk of prostate cancer (OR 0.37, P < 0.05) and high grade disease (OR 0.13, P < 0.05), whilst patients with a PSA2 increased by ≥10% had an increased risk of high‐grade prostate cancer (OR 1.93, P < 0.05). When PSA returned to normal values (<4 ng/mL) both risks of prostate cancer and high‐grade disease were reduced (OR 0.33 and 0.01, respectively, P = 0.001). Conclusion: In a cohort of Italian men undergoing prostate biopsy, a reduction of ≥20% in PSA levels significantly reduced the risk of high‐grade prostate cancer. Further multicentre studies should validate our present results. [ABSTRACT FROM AUTHOR]

This study presents a novel geo-based metric to identify neighborhoods with high burdens of prostate cancer, and compares this metric to other methods to prioritize neighborhoods for prostate cancer interventions. We geocoded prostate cancer patient data (n = 10,750) from the Pennsylvania cancer registry from 2005 to 2014 by Philadelphia census tract (CT) to create standardized incidence ratios (SIRs), mortality ratios (SMRs), and mean prostate cancer aggressiveness. We created a prostate cancer composite (PCa composite) variable to describe CTs by mean-centering and standard deviation-scaling the SMR, SIR, and mean aggressiveness variables and summing them. We mapped CTs with the 25 highest PCa composite scores and compared these neighborhoods to CTs with the 25 highest percent African American residents and the 25 lowest median household incomes. The mean PCa composite score among the 25 highest CTs was 4.65. Only seven CTs in Philadelphia had both one of the highest PCa composite scores and the highest percent African American residents. Only five CTs had both the highest PCa composites and the lowest median incomes. Mean PCa composite scores among CTs with the highest percent African American residents and lowest median incomes were 2.08 and 1.19, respectively. The PCa composite score is an accurate metric for prioritizing neighborhoods based on burden. If neighborhoods were prioritized based on percent African American or median income, priority neighborhoods would have been very different and not based on PCa burden. These methods can be utilized by public health decision-makers when tasked to prioritize and select neighborhoods for cancer interventions. [ABSTRACT FROM AUTHOR]

Purpose It has been suggested that there is a link between the dietary intake of certain nutrients and the risk of prostate cancer. The aim of this study is to examine the associations between dietary intakes of all nutrients and the risk of prostate cancer in Kermanshah.Design/methodology/approach This case-control study was conducted in Kermanshah, a province in the west of Iran in November of 2016. The sample consisted of 50 patients with confirmed prostate cancer, and 150 healthy men who matched in age with these cases and did not have any symptoms of prostate disorder were chosen as controls. Dietary intakes were collected by a semi-quantitative food frequency questionnaire that contained 147 food items and were then analyzed by Nutritionist 4 software.Findings After adjustment for potential confounding factor, highest tertile compared to lowest tertile of dietary vitamin E intake [odds ratio (OR) = 0.21; 95% confidence interval (CI) = 0.05-0.89], lycopene intake (OR = 0.11; 95% CI = 0.01-0.86) and magnesium intake (OR = 0.02; 95% CI = 0.01-0.55) had a protective effect on the incidence of prostate cancer. However, there were no associations between dietary intakes of fiber, vitamin A, vitamin D, vitamin B12, folate and calcium with prostate cancer.Originality/value The finding suggests that the dietary intakes of vitamin E, lycopene and magnesium could decrease the risk of prostate cancer. Nevertheless, dietary intake of other nutrients such as fiber, calcium, vitamins D, A, B12 and folate was not associated with prostate cancer. [ABSTRACT FROM AUTHOR]