Development and Validation of a Prostate Biopsy Risk Calculator in Black Men.

PURPOSE: We sought to develop and validate a prostate biopsy risk calculator for Black men and compare it with the Prostate Cancer Prevention Trial version 2.0, Prostate Biopsy Collaborative Group, and Kaiser Permanente Prostate Cancer Risk Calculators for the detection of Gleason Grade Group (GG) ≥ 2 prostate cancer (PCa). MATERIALS AND METHODS: We prospectively recruited 2 cohorts of men undergoing prostate biopsy from 5 facilities in Chicago. The first cohort was split into development (70%) and internal validation (30%) groups. The second was used for external validation. Iterative logistic regression was used to develop 3 models for predicting GG ≥ 2 PCa. Models were compared for discrimination using the C statistics, calibration curves, and net benefit curves. The frequency of unnecessary biopsies and missed PCas was compared at 10% and 30% risk thresholds. RESULTS: The 2 cohorts included 393 and 292 Black men, respectively. Our first model, Mistry-Sun 1, used serum PSA and prior negative biopsy. Mistry-Sun 2 added abnormal digital rectal exam (DRE) and an interaction term with abnormal DRE and PSA to Mistry-Sun 1. Mistry-Sun 3 added prostate volume, abnormal DRE, and age to Mistry-Sun 1. The C statistics were 0.74, 0.74, and 0.78, respectively, and were similar to or higher than established calculators. At the 10% and 30% risk thresholds our models had the fewest unnecessary biopsies and an appropriate proportion of missed GG ≥ 2 PCas. CONCLUSIONS: Tailoring a risk calculator to detect clinically significant PCa in Black men may improve biopsy decision-making and outcomes compared to tools developed in non-Black populations.

Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency.

A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

Vitamin D and genetic ancestry are associated with apoptosis rates in benign and malignant prostatic epithelium.

PURPOSE: Vitamin D metabolites may be protective against prostate cancer (PCa). We conducted a cross-sectional analysis to evaluate associations between in vivo vitamin D status, genetic ancestry, and degree of apoptosis using prostatic epithelial terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. EXPERIMENTAL DESIGN: Benign and tumor epithelial punch biopsies of participants with clinically localized PCa underwent indirect TUNEL staining. Serum levels of 25 hydroxyvitamin D [25(OH)D] and 1,25 dihydroxyvitamin D were assessed immediately before radical prostatectomy; levels of prostatic 25(OH)D were obtained from the specimen once the prostate was extracted. Ancestry informative markers were used to estimate the percentage of genetic West African, Native American, and European ancestry. RESULTS: One hundred twenty-one newly diagnosed men, age 40-79, were enrolled between 2013 and 2018. Serum 25(OH)D correlated positively with both tumor (ρ = 0.17, p = 0.03), and benign (ρ = 0.16, p = 0.04) prostatic epithelial TUNEL staining. Similarly, prostatic 25(OH)D correlated positively with both tumor (ρ = 0.31, p < 0.001) and benign (ρ = 0.20, p = 0.03) epithelial TUNEL staining. Only Native American ancestry was positively correlated with tumor (ρ = 0.22, p = 0.05) and benign (ρ = 0.27, p = 0.02) TUNEL staining. In multivariate regression models, increasing quartiles of prostatic 25(OH)D (ß = 0.25, p = 0.04) and Native American ancestry (ß = 0.327, p = 0.004) were independently associated with tumor TUNEL staining. CONCLUSIONS: Physiologic serum and prostatic 25(OH)D levels and Native American ancestry are positively associated with the degree of apoptosis in tumor and benign prostatic epithelium in clinically localized PCa. Vitamin D may have secondary chemoprevention benefits in preventing PCa progression in localized disease.

An editorial on a comparison of care quality metrics between Black and White men with advanced prostate cancer in the IRONMAN registry.

This editorial highlights key findings from the manuscript entitled "Experience with the US health care system for Black and White patients with advanced prostate cancer" in the Cancer journal. Namely, the Black men and White men recruited in US sites for the International Registry for Men with Advanced Prostate Cancer (IRONMAN) registry reported similar and mainly affirmative responses for health care quality metrics on a survey. In non-National Cancer Institute-designated centers, the care was actually worse for the White participants than for the Black participants. The study's results suggest that clinical trial enrollment may be a way to improve health care quality and eliminate disparities for Black men. Whether this healthcare quality benefit extends beyond the few IRONMAN recruitment sites where Black men were recruited or beyond a few measures of healthcare quality remains to be seen.

Disparities in access to robotic technology and perioperative outcomes among patients treated with radical prostatectomy.

BACKGROUND: Most radical prostatectomies are completed with robotic assistance. While studies have previously evaluated perioperative outcomes of robot-assisted radical prostatectomy (RARP), this study investigates disparities in access and clinical outcomes of RARP. STUDY DESIGN: The National Cancer Database (NCDB) was used to identify patients who received radical prostatectomy for cancer between 2010 and 2017 with outcomes through 2018. RARP was compared to open radical prostatectomy (ORP). Odds of receiving RARP were evaluated while adjusting for covariates. Overall survival was evaluated using a propensity-score matched cohort. RESULTS: Overall, 354 752 patients were included with 297 676 (83.9%) receiving RARP. Patients who were non-Hispanic Black (82.8%) or Hispanic (81.3%) had lower rates of RARP than non-Hispanic White (84.0%) or Asian patients (87.7%, p < 0.001). Medicaid or uninsured patients were less likely to receive RARP (75.5%) compared to patients with Medicare or private insurance (84.4%, p < 0.001). Medicaid or uninsured status was associated with decreased odds of RARP in adjusted multivariable analysis (OR 0.61, 95% CI 0.49-0.76). RARP was associated with decreased perioperative mortality and improved overall survival compared to ORP. CONCLUSION: Patients who were underinsured were less likely to receive RARP. Improved access to RARP may lead to decreased disparities in perioperative outcomes for prostate cancer.

Advanced glycation end-products (AGEs) are lower in prostate tumor tissue and inversely related to proportion of West African ancestry.

BACKGROUND: The metabolism of normal prostate relies on glycolysis, with prostate cancer having reduced glycolysis and increased aerobic metabolism. Advanced glycation end products (AGEs) accumulate in tissues as a result of age and glycolytic rate. Differential AGE levels were recently observed in prostate cancer tissues. Herein we sought to quantify AGEs in benign and cancer prostate tissue in a diverse cohort of patients. METHODS: Levels of the AGE Nε-(carboxylethyl)lysine (CML) were quantified by immunohistochemistry (IHC) in a tissue microarray which consisted of 3 cores from tumor and 2 cores from benign areas from 118 patients (87 African American and 31 European American). Ancestry informative markers for African Ancestry were available for 79 patients. Epithelial and stromal areas were quantified separately using an E-cadherin mask. CML levels were compared with clinical grade group and ancestry by mixed linear effect models. Age, prostate-specific antigen (PSA) levels, body mass index (BMI), and hemoglobin A1C were included as covariates. RESULTS: CML levels were lower in areas of the tumor, for both epithelium and surrounding stroma, compared with benign, but did not significantly change with tumor grade group. Age, PSA levels, BMI, and hemoglobin A1C did not associate with CML levels. CML levels were inversely associated with the percentage of African Ancestry in all tissues. CONCLUSIONS: The low CML levels in cancer may reflect the reduced glycolytic state of the tissue. The inverse relationship between African Ancestry and CML levels in both benign and cancer areas suggests a state of reduced glycolysis. It is yet to be determined whether altered glycolysis and CML levels are bystanders or drivers of carcinogenesis.

Self-Reported Race/Ethnicity Is Not Associated with Abnormal Semen Parameters after Accounting for Body Mass Index and Socioeconomic Status.

PURPOSE: We evaluated whether consideration of body mass index (BMI) and socioeconomic status alters the reported association between race/ethnicity and abnormal semen parameters. MATERIALS AND METHODS: We conducted a retrospective review of all men who underwent semen analysis (SA) for fertility evaluation at an integrated academic health care system from 2002 to 2021. Men were excluded if they had a diagnosis of Klinefelter's syndrome, history of varicocele, prior testicular surgery, prior history of chemotherapy or radiation for cancer, or prior testosterone-modulating medication use. Chi-square and Kruskal-Wallis tests were used to analyze categorical and continuous variables across self-reported racial groups, respectively. Logistic regression was used to evaluate the association between race and abnormal semen parameters according to WHO 2010 criteria, controlling for potential confounders. RESULTS: Among 2,750 men meeting inclusion criteria, 2,037 (74.1%) identified as White Non-Hispanic, 207 (7.5%) as Black Non-Hispanic, 245 (8.9%) as Hispanic and 261 (9.5%) as Asian. Median age was 35 years (IQR 32-40). Black men had an older median age (37 years, IQR 33-42, p=0.002) than other groups at the time of index SA. While Black men had higher odds of abnormal sperm concentration (OR 1.46, 95% CI 1.06-2.02, p=0.02) and abnormal total motile sperm count (OR 1.65, 95% CI 1.21-2.25, p=0.001) compared to other men after adjusting for age alone, the association of race with abnormal semen parameters was rendered insignificant with the progressive inclusion of BMI, insurance status and neighborhood income as covariates. CONCLUSIONS: In men undergoing SA for fertility evaluation, we did not see evidence of an association between race/ethnicity and abnormal semen parameters after controlling for BMI, insurance status and neighborhood income.

Assessing the accuracy of multiparametric MRI to predict clinically significant prostate cancer in biopsy naïve men across racial/ethnic groups.

INTRODUCTION: The Prostate Imaging Reporting and Data System (PIRADS) has shown promise in improving the detection of Gleason grade group (GG) 2-5 prostate cancer (PCa) and reducing the detection of indolent GG1 PCa. However, data on the performance of PIRADS in Black and Hispanic men is sparse. We evaluated the accuracy of PIRADS scores in detecting GG2-5 PCa in White, Black, and Hispanic men. METHODS: We performed a multicenter retrospective review of biopsy-naïve Black (n = 108), White (n = 108), and Hispanic (n = 64) men who underwent prostate biopsy (PB) following multiparametric MRI. Sensitivity and specificity of PIRADS for GG2-5 PCa were calculated. Race-stratified binary logistic regression models for GG2-5 PCa using standard clinical variables and PIRADS were used to calculate area under the receiver operating characteristics curves (AUC). RESULTS: Rates of GG2-5 PCa were statistically similar between Blacks, Whites, and Hispanics (52.8% vs 42.6% vs 37.5% respectively, p = 0.12). Sensitivity was lower in Hispanic men compared to White men (87.5% vs 97.8% respectively, p = 0.01). Specificity was similar in Black versus White men (21.6% vs 27.4%, p = 0.32) and White versus Hispanic men (27.4% vs 17.5%, p = 0.14). The AUCs of the PIRADS added to standard clinical data (age, PSA and suspicious prostate exam) were similar when comparing Black versus White men (0.75 vs 0.73, p = 0.79) and White versus Hispanic men (0.73 vs 0.59, p = 0.11). The AUCs for the Base model and PIRADS model alone were statistically similar when comparing Black versus White men and White versus Hispanic men. CONCLUSIONS: The accuracy of the PIRADS and clinical data for detecting GG2-5 PCa seems statistically similar across race. However, there is concern that PIRADS 2.0 has lower sensitivity in Hispanic men compared to White men. Prospective validation studies are needed.

Prevalence of prostate cancer at autopsy in Nigeria-A preliminary report.

BACKGROUND AND OBJECTIVES: Prostate cancer is the most commonly diagnosed cancer in Nigerian men despite the lack of PSA based screening. Current prevalence estimates in Nigeria are based on cancer registry data obtained primarily from hospital admissions and therefore not truly reflective of prostate cancer incidence. Prior autopsy series did not adhere to modern pathologic quality practices. The aim of this study was to explore the prevalence of asymptomatic prostate cancer among Nigerian men at the time of autopsy. METHODS: Prostates were collected at autopsy at the Universities of Lagos and Calabar Teaching Hospitals from men aged more than 40 who died from causes other than prostate cancer. Thirty-nine prostates from Nigerian men autopsied in 2017 to 2018 were formalin-fixed, weighed, and sliced at 4 mm intervals. Haematoxylin and eosin-stained paraffin sections were prepared from these slices. Presence and Gleason grade of prostatic adenocarcinomas and presence of high-grade prostatic intraepithelial neoplasia (HGPIN) were recorded. RESULTS: Mean age of cases was 55 ± 11 years and mean prostatic weight was 23.0 ± 10.9 g. The crude prevalence of HGPIN was 20.6%. Overall crude prevalence of prostate cancer was 8.8% (n = 34), increasing from 8.3% for men aged 40-59 (n = 23) to 10.0% for men ≥60 years old (n = 10). Two tumors were small and had Gleason Grade 3 + 3 or 3 + 4, and one large stage T3 tumor with Gleason Grade 4 + 3 disease and neuroendocrine appearance was found in a 54-year-old man. CONCLUSIONS: The 8.8% prevalence of subclinical prostate cancer at autopsy was similar to previously reported Nigerian studies with more limited tissue sampling (6.7%-10%), but considerably lower than estimates in other populations, including African Americans. Our findings suggest that latent, clinically asymptomatic prostate cancer is less frequent in Nigerians than in African Americans, despite shared genetic ancestry. Future studies with increased sample size are warranted to provide insight in the natural history and true prevalence of prostate cancer in West Africa.

Performance of Prostate Health Index in Biopsy Naïve Black Men.

PURPOSE: The Prostate Health Index is validated for prostate cancer detection but has not been well validated for Gleason grade group 2-5 prostate cancer detection in Black men. We hypothesize that the Prostate Health Index has greater accuracy than prostate specific antigen for detection of Gleason grade group 2-5 prostate cancer. We estimated probability of overall and Gleason grade group 2-5 prostate cancer across previously established Prostate Health Index ranges and identified Prostate Health Index cutoffs that maximize specificity for Gleason grade group 2-5 prostate cancer with sensitivity >90%. MATERIALS AND METHODS: We recruited a "cancer-free" Black control cohort (135 patients) and a cohort of biopsy naïve Black men (158) biopsied for elevated prostate specific antigen. Descriptive statistics compared the prostate cancer cases and controls and the frequency of Gleason grade group 2-5 prostate cancer across Prostate Health Index scores. Receiver operating characteristics compared the discrimination of prostate specific antigen, Prostate Health Index and other prostate specific antigen related biomarkers. Sensitivity and specificity for Gleason grade group 2-5 prostate cancer detection were assessed at prostate specific antigen and Prostate Health Index thresholds alone and in series. RESULTS: Of biopsied subjects 32.9% had Gleason grade group 2-5 prostate cancer. In Blacks with prostate specific antigen from 4.0-10.0 ng/ml, Prostate Health Index and prostate specific antigen had similar discrimination for Gleason grade group 2-5 prostate cancer (0.63 vs 0.57, p=0.27). In Blacks with prostate specific antigen ≤10.0, a threshold of prostate specific antigen ≥4.0 had 90.4% sensitivity for Gleason grade group 2-5 prostate cancer; a threshold of prostate specific antigen ≥4.0 with Prostate Health Index ≥35.0 in series avoided unnecessary biopsy in 33.0% of men but missed 17.3% of Gleason grade group 2-5 prostate cancer. Prostate specific antigen ≥4.0 with Prostate Health Index ≥28.0 in series spared biopsy in 17.9%, while maintaining 90.4% sensitivity of Gleason grade group 2-5 prostate cancer. CONCLUSIONS: The Prostate Health Index has moderate accuracy in detecting Gleason grade group 2-5 prostate cancer in Blacks, but Prostate Health Index ≥28.0 can be safely used to avoid some unnecessary biopsies in Blacks.

A case report of Nocardia spp. infective endocarditis in an injection drug user.

BACKGROUND: Nocardia-related endocarditis is rare. Intravenous drug use with nonsterile injection practices is a potential risk factor for nocardia infection. Disseminated nocardiosis with endovascular involvement is rarely reported in immunocompetent individuals. CASE PRESENTATION: A 54-year-old male was diagnosed with infective endocarditis due to Nocardia asteroides with septic emboli in the brain and spleen. The use of a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) rapid diagnostic system was beneficial in identifying the causative organism. He was empirically treated with combination therapy consisting of three antibiotics. Antimicrobial susceptibility testing indicated that all three antibiotics had favorable minimum inhibitory concentrations (MICs). Due to his clinical status, he was not a surgical candidate. Patient passed away after discharge to hospice. CONCLUSIONS: This case demonstrates unique challenges in the identification, diagnosis, and management of Nocardia-related infective endocarditis. A detailed history of injection practices should guide clinicians in assessing the risk for environmental pathogens. Valvular surgery and combination antibiotic therapy should be recommended for all eligible patients to improve the chances of survival.

Complications of cranioplasty following decompressive craniectomy for traumatic brain injury: systematic review and meta-analysis.

BACKGROUND: Decompressive craniectomy (DC) is a common neurosurgical intervention for severe traumatic brain injury (TBI), as well as malignant stroke, malignancy and infection. DC necessitates subsequent cranioplasty. There are significant demographic differences between TBI and non-TBI patients undergoing cranioplasty, which may influence their relative risk profiles for infection, aseptic bone flap resorption (aBFR) and re-operation. OBJECTIVE: Perform a meta-analysis to determine the relative infection, aBFR and re-operation risk profiles of TBI patients as compared to other indications for DC. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, EMBASE and Google Scholar were searched until 26/11/2020. Studies detailing rates of infection, re-operation and/or aBFR in specific materials and the post-TBI population were included, while studies in paediatrics or craniosynostosis repair were excluded. RESULTS: Twenty-six studies were included. There was no difference in relative risk of infection between TBI and non-TBI cohorts (RR 0.81, 95% CI 0.57-1.17), with insignificant heterogeneity (I2 = 33%). TBI was a risk factor for aBFR (RR 1.54, 95% CI 1.25-1.89), with no significant heterogeneity (I2 = 13%). TBI was a risk factor for re-operation in the autologous sub-group (RR 1.49, 95% CI 1.05-2.11) but not in the alloplastic sub-group (RR = 0.86, 95% CI 0.34-2.18). Heterogeneity was insignificant (I2 = 11%). CONCLUSION: TBI is a risk factor for aBFR and re-operation following cranioplasty. Use of an alloplastic graft for primary cranioplasty in these patients may partially mitigate this increased risk.

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (odds ratio = 0.18; 95% CI, 0.03-0.89; P = 0.044). Correlation of miR-182 with mRNA expression in laser-capture microdissected benign prostate epithelium was used to predict prostatic miR-182 targets. Genes that were negatively correlated with miR-182 were enriched for its predicted targets and for genes previously identified as up-regulated in prostate cancer metastases. miR-182 expression was also negatively correlated with genes previously identified as up-regulated in primary prostate tumors from African American patients, who are at an increased risk of developing aggressive prostate cancer. Taken together, these results suggest that although miR-182 is expressed at higher levels in localized prostate cancer, its levels are lower in aggressive cancers, suggesting a biphasic role for this miRNA that may be exploited for prognostic and/or therapeutic purposes to reduce prostate cancer progression.

Physiologic serum 1,25 dihydroxyvitamin D is inversely associated with prostatic Ki67 staining in a diverse sample of radical prostatectomy patients.

PURPOSE: To investigate the correlation between serum 25 hydroxyvitamin D, prostatic 25 hydroxyvitamin D, and serum 1,25 dihydroxyvitamin D, and their respective associations with prostatic tumor proliferation at the time of radical prostatectomy. METHODS: In this cross-sectional analysis of 119 men undergoing radical prostatectomy, serum from whole blood and expressed prostatic fluid was collected on the day of surgery. Tumor proliferation was measured in the dominant tumor on formalin-fixed prostatectomy tissues by immunohistochemical staining for Ki67 and quantified by Aperio imaging analysis. RESULTS: The sample included 88 African Americans (74%) and 31 (26%) European Americans. Serum and prostatic levels of 25 hydroxyvitamin D were correlated with each other (Spearman's rho (ρ) = 0.27, p = 0.004), and there was also a correlation between serum 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D (ρ = 0.34, p < 0.001). Serum and prostatic 25 hydroxyvitamin D levels were not correlated with Ki67 staining in tumor cells. Serum 1,25 dihydroxyvitamin D was inversely correlated with Ki67 staining in tumor cells (ρ = - 0.30, p = 0.002). On linear regression, serum 1,25 dihydroxyvitamin D was negatively associated with Ki67 staining in tumor cells (ß - 0.46, 95% CI - 0.75, - 0.04, p = 0.04). CONCLUSION: The correlation between physiologic serum levels of 25 hydroxyvitamin D with both prostatic 25 hydroxyvitamin D and serum 1,25 dihydroxyvitamin D suggests that serum levels are reasonable biomarkers of vitamin D status. Furthermore, serum 1,25 dihydroxyvitamin D has an inverse association with Ki67 staining in tumor cells at physiologic levels and may protect against tumor progression.

A comparative effectiveness analysis of the PBCG vs. PCPT risks calculators in a multi-ethnic cohort.

BACKGROUND: Predictive models that take race into account like the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPT RC) and the new Prostate Biopsy Collaborative Group (PBCG) RC have been developed to equitably mitigate the overdiagnosis of prostate specific antigen (PSA) screening. Few studies have compared the performance of both calculators across racial groups. METHODS: From 1485 prospectively recruited participants, 954 men were identified undergoing initial prostate biopsy for abnormal PSA or digital rectal examination in five Chicago hospitals between 2009 and 2014. Discrimination, calibration, and frequency of avoided biopsies were calculated to assess the performance of both risk calculators. RESULTS: Of 954 participants, 463 (48.5%) were Black, 355 (37.2%) were White, and 136 (14.2%) identified as Other. Biopsy results were as follows: 310 (32.5%) exhibited no cancer, 323 (33.9%) indolent prostate cancer, and 321 (33.6%) clinically significant prostate cancer (csPCa). Differences in area under the curve (AUC)s for the detection of csPCa between PCPT and PBCG were not statistically different across all racial groups. PBCG did not improve calibration plots in Blacks and Others, as it showed higher levels of overprediction at most risk thresholds. PCPT led to an increased number of avoidable biopsies in minorities compared to PBCG at the 30% threshold (68% vs. 28% of all patients) with roughly similar rates of missed csPCa (23% vs. 20%). CONCLUSION: Significant improvements were noticed in PBCG's calibrations and net benefits in Whites compared to PCPT. Since PBCG's improvements in Blacks are disputable and potentially biases a greater number of low risk Black and Other men towards unnecessary biopsies, PCPT may lead to better biopsy decisions in racial minority groups. Further comparisons of commonly used risk calculators across racial groups is warranted to minimize excessive biopsies and overdiagnosis in ethnic minorities.

Genome-wide scan of 29,141 African Americans finds no evidence of directional selection since admixture.

The extent of recent selection in admixed populations is currently an unresolved question. We scanned the genomes of 29,141 African Americans and failed to find any genome-wide-significant deviations in local ancestry, indicating no evidence of selection influencing ancestry after admixture. A recent analysis of data from 1,890 African Americans reported that there was evidence of selection in African Americans after their ancestors left Africa, both before and after admixture. Selection after admixture was reported on the basis of deviations in local ancestry, and selection before admixture was reported on the basis of allele-frequency differences between African Americans and African populations. The local-ancestry deviations reported by the previous study did not replicate in our very large sample, and we show that such deviations were expected purely by chance, given the number of hypotheses tested. We further show that the previous study's conclusion of selection in African Americans before admixture is also subject to doubt. This is because the FST statistics they used were inflated and because true signals of unusual allele-frequency differences between African Americans and African populations would be best explained by selection that occurred in Africa prior to migration to the Americas.

Race and BMI modify associations of calcium and vitamin D intake with prostate cancer.

BACKGROUND: African Americans have disproportionately higher burden of prostate cancer compared to European Americans. However, the cause of prostate cancer disparities is still unclear. Several roles have been proposed for calcium and vitamin D in prostate cancer pathogenesis and progression, but epidemiologic studies have been conducted mainly in European descent populations. Here we investigated the association of calcium and vitamin D intake with prostate cancer in multiethnic samples. METHODS: A total of 1,657 prostate cancer patients who underwent screening and healthy controls (888 African Americans, 620 European Americans, 111 Hispanic Americans, and 38 others) from Chicago, IL and Washington, D.C. were included in this study. Calcium and vitamin D intake were evaluated using food frequency questionnaire. We performed unconditional logistic regression analyses adjusting for relevant variables. RESULTS: In the pooled data set, high calcium intake was significantly associated with higher odds for aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 1.98, 95% C.I.: 1.01-3.91), while high vitamin D intake was associated with lower odds of aggressive prostate cancer (ORQuartile 1 vs. Quartile 4 = 0.38, 95% C.I.: 0.18-0.79). In African Americans, the association between high calcium intake and aggressive prostate cancer was statistically significant (ORQuartile 1 vs. Quartile 4 = 4.28, 95% C.I.: 1.70-10.80). We also observed a strong inverse association between total vitamin D intake and prostate cancer in African Americans (ORQuartile 1 vs. Quartile 4 = 0.06, 95% C.I.: 0.02-0.54). In European Americas, we did not observe any significant associations between either calcium or vitamin D intake and prostate cancer. In analyses stratifying participants based on Body Mass Index (BMI), we observed a strong positive association between calcium and aggressive prostate cancer and a strong inverse association between vitamin D intake and aggressive prostate cancer among men with low BMI (<27.8 kg/m2), but not among men with high BMI (≥27.8 kg/m2). Interactions of race and BMI with vitamin D intake were significant (P Interaction < 0.05). CONCLUSION: Calcium intake was positively associated with aggressive prostate cancer, while vitamin D intake exhibited an inverse relationship. However, these associations varied by race/ethnicity and BMI. The findings from this study may help develop better prostate cancer prevention and management strategies.

The landscape of recombination in African Americans.

Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.

African-American Prostate Cancer Disparities.

PURPOSE OF REVIEW: The purpose of this review is to examine prostate cancer racial disparities specific to the African-American population. RECENT FINDINGS: African-American men are more likely to be diagnosed with prostate cancer, present at an earlier age; are more likely to have locally advanced or metastatic disease at diagnosis; and have suboptimal outcomes to standard treatments. Prostate cancer treatment requires a nuanced approach, particularly when applying screening, counseling, and management of African-American men. Oncological as well as functional outcomes may differ and are potentially due to a combination of genetic, molecular, behavioral, and socioeconomic factors.