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Figure S1. Cross-validation error in ADMIXTURE analyses. The best fit to data occurs at K = 3.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array.Significance:This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

Successfully called markers on the MADCaP Array. This tab-delimited file includes genomic positions, inclusion criteria, and overlap with other arrays.

Background The immune system plays an important role in the pathogenesis of Alzheimer disease (AD), but it remains unclear whether bacillus Calmette-Guerin (BCG) may affect the risk of AD or not. Methods Using retrospective chart review, we collected data regarding demographics, comorbidities, cancer diagnosis, BCG treatment, and subsequent diagnosis of AD or other dementia in a racially/ethnically diverse cohort of patients with non–muscle-invasive bladder cancer (NIMBC) receiving treatment between 1984 and 2020 in the Bronx, New York. We used Cox proportional hazard models to examine association between BCG treatment and risk of incident AD or other dementia, adjusting for age, gender, race/ethnicity, and major comorbidities. Results In our cohort of 1290 patients with NMIBC, a total of 99 (7.7%) patients developed AD or other dementia during follow-up. Patients who received BCG treatment (25%) had a 60% lowered incidence of AD or other dementia (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21-0.80) in comparison to those who did not receive BCG. There was also suggestive evidence that the reduction in risk of AD or other dementia associated with BCG treatment was stronger in men (adjusted HR, 0.34; 95% CI, 0.15-0.81) but not in women (adjusted HR, 0.75; 95% CI 0.25-2.24). When we stratified the patients who received BCG by type of treatments, patients who received both induction and maintenance rounds of BCG had a further lowered incidence of AD or other dementia (HR, 0.23; 95% CI, 0.06-0.96) than patients who did not receive BCG. Conclusions To our knowledge, our study is one of the first to suggest that BCG treatment is associated with a reduced risk of developing AD or other dementia in a multiethnic population, independent of significant comorbidities. Larger cohort studies are needed to corroborate our findings.

PURPOSE: African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. METHODS: Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multicenter, hospital-based case-control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. RESULTS: Among controls 16.4% were obese (BMI≥30 kg/m(2)), 26% and 90% had WC>97 cm and WHR>0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive disease, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR=1.38, 95%CI 0.99–1.93), and central obesity (WC>97cm: OR=1.60, 95%CI 1.10-2.33; and WHtR >0.59: OR=1.68, 95%CI 1.24-2.29) were positively associated with D’Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. DISCUSSION: The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

Finasteride use has been associated with a reduced incidence of bladder cancer. However, the majority of studies have been conducted primarily in East Asian or White populations. Given differences in the incidence of bladder cancer among racial/ethnic groups, it is important to determine whether the effect of finasteride use on bladder cancer varies by race/ethnicity.We identified all patients with a diagnosis of benign prostatic hyperplasia between 2000 and 2016 at our academic health center in Bronx, New York via an electronic medical record database. We then identified patients who were prescribed finasteride, and those who developed bladder cancer during followup. We used competing risk analysis to examine associations of finasteride use with risk of bladder cancer, adjusting for age, smoking and race/ethnicity.We identified 42,406 patients with benign prostatic hyperplasia (average±SD age 67±12.9 years), of whom 27.7% were Black and 14.8% were Hispanic. Finasteride was prescribed in 5,698 patients (13.4%). Bladder cancer was diagnosed in 84 of 5,698 finasteride users (1.5%), compared to 762 of 36,708 nonusers (2.1%, log-rank p=0.003). Finasteride was associated with a 36% reduction in risk of bladder cancer (HR: 0.64, 95% CI: 0.51-0.80; p0.0001) among all patients. When data were stratified by race/ethnicity, finasteride use was associated with a reduction in risk of bladder cancer in White men (HR: 0.61, 95% CI: 0.43-0.86; p=0.005) and Hispanic men (HR: 0.44, 95% CI: 0.21-0.90; p=0.026), but there was no association among Black men (HR: 1.01, 95% CI: 0.67-1.51; p=0.964).Our study corroborates previous findings that men who are on finasteride have a lower bladder cancer incidence. However, the reduction in risk was seen only in White and Hispanic men, but not among Black men. Therefore, race/ethnicity represents an important stratification factor for future larger studies on finasteride as chemoprevention for bladder cancer.

Several studies have reported associations between vascular calcifications and urinary stone disease (USD). However, results have been inconsistent and the majority of studies did not report on race/ethnicity. We examined the association between vascular calcifications and USD in a large, racially/ethnically diverse patient population. We identified 672 USD cases and 672 controls (i.e., patients without a history of USD) from patients who underwent non-contrast CT imaging at Montefiore Medical Center in Bronx, New York between 2004 and 2013. Controls were matched to cases on age, sex and race/ethnicity. The non-contrast CT imaging was used to measure abdominal aortic calcification (AAC) and calculate the AAC severity score. Logistic regression models were used to examine associations of AAC presence and severity score with risks of USD and stone types. Cases and controls had similar AAC prevalence (45.2% vs. 44.8%, p = 0.87), and AAC severity score (median 10 vs. 9.3, p = 0.47). The presence of AAC (OR = 0.98, 95% CI 0.78–1.23; p = 0.86) or AAC severity score were not associated with risk of USD: ORs of 0.96, 0.87, 1.07 and 1.03 for increasing AAC quartiles (p-trend = 0.54). There were also no associations in the stratified analyses by race/ethnicity or by sex. However, when USD patients were stratified by stone type, brushite/apatite stone formers had an inverse association with the lowest quartile of AAC severity score (OR = 0.35, 95% CI 0.11–0.84, p = 0.04) in comparison to patients without AAC. Overall, we found no association between vascular calcifications and risk of urinary stone disease in this large, hospital-based, case–control study.

PURPOSE Seropositivity for the HPV16-E6 oncoprotein is a promising marker for early detection of oropharyngeal cancer (OPC), but the absolute risk of OPC after a positive or negative test is unknown. METHODS We constructed an OPC risk prediction model that integrates (1) relative odds of OPC for HPV16-E6 serostatus and cigarette smoking from the human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population risk factor data from the National Health Interview Survey, and (3) US sex-specific population rates of OPC and mortality. RESULTS The nine HPVC3 cohorts included 365 participants with OPC with up to 10 years between blood draw and diagnosis and 5,794 controls. The estimated 10-year OPC risk for HPV16-E6 seropositive males at age 50 years was 17.4% (95% CI, 12.4 to 28.6) and at age 60 years was 27.1% (95% CI, 19.2 to 45.4). Corresponding 5-year risk estimates were 7.3% and 14.4%, respectively. For HPV16-E6 seropositive females, 10- year risk estimates were 3.6% (95% CI, 2.5 to 5.9) at age 50 years and 5.5% (95% CI, 3.8 to 9.2) at age 60 years and 5-year risk estimates were 1.5% and 2.7%, respectively. Over 30 years, after a seropositive result at age 50 years, an estimated 49.9% of males and 13.3% of females would develop OPC. By contrast, 10-year risks among HPV16-E6 seronegative people were very low, ranging from 0.01% to 0.25% depending on age, sex, and smoking status. CONCLUSION We estimate that a substantial proportion of HPV16-E6 seropositive individuals will develop OPC, with 10-year risks of 17%-27% for males and 4%-6% for females age 50-60 years in the United States. This high level of risk may warrant periodic, minimally invasive surveillance after a positive HPV16-E6 serology test, particularly for males in high-incidence regions. However, an appropriate clinical protocol for surveillance remains to be established., United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) 5U01CA195603-02 U01CA202979, Division of Cancer Epidemiology and Genetics, US NCI, VicHealth, Canadian Institutes of Health Research (CIHR), Cancer Council Victoria, National Health and Medical Research Council (NHMRC) of Australia 209057 396414 1074383, National Cancer Institute P30 CA016056, Einstein Cancer Research Center CA013330, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA, NIH National Heart Lung & Blood Institute (NHLBI) 75N92021D00001 75N92021D00002 75N92021D00003 75N92021D00004 75N92021D00005

Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in HIV-positive individuals even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in HIV-positive adults with cryptococcal antigenemia is unknown.Cryptococcus spp. capsular glucuronoxylomannan (GXM)- and naturally occurring β-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans living with HIV who underwent CrAg screening and were prospectively followed up to 6 months. Associations between antibody titers, CrAg status and all-cause mortality were sought using logistic and Cox proportional hazards regression, respectively.Compared to CrAg-negative (n = 130), CrAg-positive individuals (n = 67) had significantly higher IgG1 (median, 6,672 [interquartile range, IQR, 4,696-10,414] vs. 5,343 [3,808-7,722]μg/ml; P = 0.007), IgG2 (1,467 [813-2,607] vs. 1,036 [519-2,012]μg/ml; P = 0.01), GXM-IgG (1:170 [61-412] vs. 1:117 [47-176]; P = 0.0009) and lower curdlan-IgG (1:47 [11-133] vs. 1:93 [40-206]; P = 0.01) titers. GXM-IgG associated directly with cryptococcal antigenemia adjusted for CD4 count and antiretroviral therapy use (odds ratio, 1.64 for each log increase in titer; 95% confidence interval [CI], 1.21-2.22). Among CrAg-positive individuals, GXM-IgG inversely associated with mortality at 6 months adjusted for CD4 count and active or prevalent tuberculosis (hazard ratio, 0.50; a two-fold reduction per log increase in titer; 95% CI, 0.33-0.77).The finding of an inverse association of GXM-IgG with mortality in CrAg-positive individuals suggests that GXM-IgG titer may have prognostic value in such individuals. Prospective longitudinal studies of antibody levels to investigate this hypothesis and identify mechanisms by which antibody may protect against mortality are warranted.

Small renal masses (SRMs) are often incidentally diagnosed, and a large proportion are malignant. However, there is a paucity of data describing predictors of malignancy in minority patients with SRMs. Thus, our goal was to examine clinical risk factors associated with SRM malignant histology in patients undergoing partial nephrectomy (PN) a diverse, urban academic center.Patients with a SRM undergoing PN at a single institution between 2010 to 2018 were reviewed. Demographic, clinical, and imaging characteristics were compared to pathology results. Logistic regression was used to examine associations between demographic/clinical variables for malignant and high-grade histology.In total, 331 patients who underwent PN for SRM were included. Of those, 264 (79.8%) had malignant histology while 67 (20.2%) had benign histology. The proportions of men and of current smokers were significantly higher among patients with malignant histology. In multivariate models, non-Hispanic Black (NHB) patients had increased odds of having malignant histology (OR 2.46, 95% CI: 1.01-5.99, P = .048) and current smokers (OR = 4.02; 95% CI 1.14-14.18, P = .031). Hispanic patients had a 3-fold increased risk of high-grade RCC (OR 3.06, 95% CI: 1.19-7.87, P = 0.02) compared to Non-Hispanic White patients.In our population, male sex, smoking, and NHB race/ethnicity was associated with an increased risk of malignancy in patients undergoing partial nephrectomy for SRM. Older age and Hispanic race/ethnicity were associated with high grade RCC. Our results suggest that urologists should exercise a higher level of vigilance in managing and treating SRM among NHB and Hispanic patients.

Fractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma. A retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models. A higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (β = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (β = 16.1, 95% CI: 1.5 to 30.8). Intermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children.

Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

INTRODUCTION AND OBJECTIVE:The immune system plays an important role in the pathogenesis of Alzheimer’s disease (AD). Intravesical BCG therapy for non-muscle invasive bladder cancer (NMIBC) has bee...

INTRODUCTION AND OBJECTIVE:Overactive Bladder (OAB) is diagnosed based on symptoms and often treated based on patient preference. A urine biomarker could phenotype refractory OAB and identify those...

INTRODUCTION AND OBJECTIVE:Overactive bladder (OAB) is diagnosed clinically based on symptoms. However, a biomarker may help provide objective measurement of disease severity and improvement after ...

INTRODUCTION AND OBJECTIVE:Men of African descent have the highest burden of aggressive prostate cancer (PCa). However, the clinical features of PCa within sub-Saharan Africa (SSA) are understudied...

Objective To perform a systematic review and a retrospective cohort analysis evaluating the rates of surgical downgrading of prostate cancer (PCa) from biopsy (PBx) to radical prostatectomy (RP), and their association with biochemical recurrence (BCR) in a multiethnic population. Methods A systematic review of PubMed and other databases was performed. We included retrospective studies evaluating the relationship between surgical downgrading and BCR-free survival. Data regarding Gleason score (GL) downgrading were abstracted from the articles and categorized as follows: GL8-10 to GL7, GL7 to GL6, and GL 7(4 + 3) to GL7(3 + 4). We also performed a retrospective cohort review of patients who underwent RP at our institution from 2005 through 2020. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare BCR among downgraded versus non-downgraded men. Results Systematic review yielded 137 abstracts; of these, 36 full-texts were reviewed, 8 of which were included in our systematic review. Despite substantial variability, all showed that GL at RP is one of the most important factors of BCR-free survival. A total of 1,484 men with PCa were analyzed from our institution. On multivariate analysis, GL7 to GL6 downgrading (HR = 0.50, p = 0.022) and GL8-10 to GL7 downgrading (HR = 0.42, p = 0.011) were associated with reduced risk of BCR when compared to men with GL7 and GL8-10 concordance, respectively. However, GL7(4 + 3) to GL7(3 + 4) downgrading was not significantly associated with reduced BCR (HR = 0.56, p = 0.12), when compared to GL7(4 + 3) concordance, although HR was similar. Conclusion Surgical downgrading at RP was associated with a reduced risk of BCR compared to GL concordant disease, and these findings have been validated within our multiethnic population. Pathologic downgrading at the time of RP may be a more useful predictor of subsequent BCR in comparison to that associated with GL concordant pathology.

INTRODUCTION: We sought to determine if outcomes of Bacillus Calmette-Guerin (BCG) therapy in patients with non-muscle-invasive bladder cancer (NMIBC) vary by race. METHODS: A retrospective chart review was conducted on 149 patients treated with BCG for intermediate- and high-risk NMIBC between 2001 and 2018, and who were followed up for cancer recurrence through March 2019. The primary outcomes were disease-free survival (DFS), low-grade disease-free survival (LGDFS), high-grade disease-free survival (HGDFS), and progression-free survival (PFS) at five years. Kaplan-Meier survival curves stratified by race (African American vs non-African American) were analyzed for all the above outcomes and multivariate Cox regression analyses were also performed to compare recurrence differences by race, after adjusting for age, sex, initial stage and grade. RESULTS: Of the 149 patients, 37.6% were Caucasian, 24.8% were African American, 26.8% were Hispanic, and 10.7% were of other/unknown race. Disease stage at initial presentation was 65.1% Ta, 34.9% T1, and 18.1% CIS. African American patients (N=37) did not have evidence for worse outcomes compared to non-African American patients when considering DFS (54.1% vs. 65.7%, p = 0.202), HGDFS (58.8% vs. 71.7%, p = 0.158), and PFS (83.8% vs. 92.6%, p = 0.117) at five years. Multivariate analysis did not reveal statistically significant racial differences in recurrence or progression. CONCLUSIONS: African Americans with NMIBC did not have worse disease recurrence and progression after receiving intravesical BCG treatment. Although there did appear to be a trend towards worse oncologic outcomes in African Americans, larger studies are needed to validate this finding.

Background Increased cancer risk has been reported in Parkinson's disease (PD) patients carrying the leucine rich repeat kinase 2 (LRRK2) G2019S mutation (LRRK2-PD) in comparison with idiopathic PD (IPD). It is unclear whether the elevated risk would be maintained when compared with unaffected controls. Methods Cancer outcomes were compared among 257 LRRK2-PD patients, 712 IPD patients, and 218 controls recruited from 7 LRRK2 consortium centers using mixed-effects logistic regression. Data were then pooled with a previous study to examine cancer risk between 401 LRRK2-PD and 1946 IPD patients. Results Although cancer prevalence was similar among LRRK2-PD patients (32.3%), IPD patients (27.5%), and controls (27.5%; P = 0.33), LRRK2-PD had increased risks of leukemia (odds ratio [OR] = 4.55; 95% confidence interval [CI], 1.46-10.61) and skin cancer (OR = 1.61; 95% CI, 1.09-2.37). In the pooled analysis, LRRK2-PD patients had also elevated risks of leukemia (OR = 9.84; 95% CI, 2.15-44.94) and colon cancer (OR = 2.34; 95% CI, 1.15-4.74) when compared with IPD patients. Conclusions The increased risks of leukemia as well as skin and colon cancers among LRRK2-PD patients suggest that LRRK2 mutations heighten risks of certain cancers. (c) 2019 International Parkinson and Movement Disorder Society

To determine whether patients with ureteral stones received different standard of care in the emergency department (ED) according to various sociodemographic factors. We conducted a retrospective study of patients presenting to EDs in a large tertiary-care hospital in the Bronx, New York with a diagnosis of ureteral stones. Electronic chart review was used to assess each patient’s ED course and to gather socio-demographic information. The primary outcomes of interest were administration of pain medication, prescription of alpha-1 antagonists to facilitate stone passage, and whether or not patients received CT scan or ultrasound. Associations of these outcomes with age categories, sex, race/ethnicity, BMI category, socioeconomic status and insurance status were examined using multivariate logistic regression models. 1200 patients were included in this analysis of which 616 (51%) were women. A large proportion of patients were minorities: 40% Hispanic, 15% non-Hispanic Black, and 20% other/multiracial. Patients aged 55–64 years and those 65 or older were less likely to receive pain medication compared to patients

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.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.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/mIn 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.

NonHispanic Black (NHB) and Hispanic/Afro-Caribbean men have the highest risk of prostate cancer (PCa) compared to nonHispanic White (NHW) men. However, ethnicity-specific outcomes of targeted fusion biopsy (FB) for the detection of PCa are poorly characterized. We compared the outcomes of FB by Prostate Imaging Reporting and Data System (PI-RADS®) score and race/ethnicity among a diverse population.We evaluated all men who underwent image-guided FB for suspicious lesions on prostate magnetic resonance imaging (≥PI-RADS 3) over a 2-year period. We examined associations of race/ethnicity and PI-RADS score with risk of PCa or clinically significant PCa (cs-PCa, Gleason Group ≥2) on FB using mixed-effects logistic regression models.A total of 410 men with 658 lesions were analyzed, with 201 (49.0%) identified as NHB and 125 (30.5%) identified as Hispanic. NHB men had a twofold increase in the odds of detecting cs-PCa (OR=2.7, p=0.045), while Hispanic men had similar odds of detecting cs-PCa compared to NHW men. With regard to all PCa, NHB men had a similar increase in the odds of detecting all PCa (OR=2.4, p=0.050), which was borderline statistically significant compared to NHW men on FB. When we excluded men on active surveillance, NHB men had even stronger associations with detection of cs-PCa (OR=3.10, p=0.047) or all PCa (OR=2.77, p=0.032) compared to NHW men.NHB men have higher odds for overall PCa and cs-PCa on FB compared to NHW men. Further work may clarify differences per PI-RADS score. Clinicians should interpret prostate magnetic resonance imaging lesions with more caution in NHB men.

Several studies have reported associations between vascular calcifications and urinary stone disease (USD). However, results have been inconsistent and the majority of studies did not report on race/ethnicity. We examined the association between vascular calcifications and USD in a large, racially/ethnically diverse patient population. We identified 672 USD cases and 672 controls (i.e., patients without a history of USD) from patients who underwent non-contrast CT imaging at Montefiore Medical Center in Bronx, New York between 2004 and 2013. Controls were matched to cases on age, sex and race/ethnicity. The non-contrast CT imaging was used to measure abdominal aortic calcification (AAC) and calculate the AAC severity score. Logistic regression models were used to examine associations of AAC presence and severity score with risks of USD and stone types. Cases and controls had similar AAC prevalence (45.2% vs. 44.8%, p = 0.87), and AAC severity score (median 10 vs. 9.3, p = 0.47). The presence of AAC (OR = 0.98, 95% CI 0.78-1.23; p = 0.86) or AAC severity score were not associated with risk of USD: ORs of 0.96, 0.87, 1.07 and 1.03 for increasing AAC quartiles (p-trend = 0.54). There were also no associations in the stratified analyses by race/ethnicity or by sex. However, when USD patients were stratified by stone type, brushite/apatite stone formers had an inverse association with the lowest quartile of AAC severity score (OR = 0.35, 95% CI 0.11-0.84, p = 0.04) in comparison to patients without AAC. Overall, we found no association between vascular calcifications and risk of urinary stone disease in this large, hospital-based, case-control study.

Background Severe coronavirus disease 2019 (COVID‐19) is characterized by a proinflammatory state with high mortality. Statins have anti‐inflammatory effects and may attenuate the severity of COVID‐19. Methods and Results An observational study of all consecutive adult patients with COVID‐19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020. Patients were grouped as those who did and those who did not receive a statin, and in‐hospital mortality was compared by competing events regression. In addition, propensity score matching and inverse probability treatment weighting were used in survival models to examine the association between statin use and death during hospitalization. A total of 4252 patients were admitted with COVID‐19. Diabetes mellitus modified the association between statin use and in‐hospital mortality. Patients with diabetes mellitus on a statin (n=983) were older (69±11 versus 67±14 years; P P P P =0.82). Propensity score matching (hazard ratio, 0.88; 95% CI, 0.83–0.94; P P Conclusions Statin use was associated with reduced in‐hospital mortality from COVID‐19 in patients with diabetes mellitus. These findings, if validated, may further reemphasize administration of statins to patients with diabetes mellitus during the COVID‐19 era.

Background In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. Methods Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). Results In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. Conclusions We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

BACKGROUND The opioid epidemic has been influenced in part by physician overprescribing. Several studies have evaluated opioid use after urogynecologic surgery, with limited data on postoperative guidelines. The objective of this study was to investigate the effect of implementing a multimodal, opioid-sparing analgesia regimen on opioid use, patient satisfaction, and refill rates. MATERIALS AND METHODS This was a retrospective observational study of female patients undergoing urogynecologic surgery at an academic center from 2017 to 2019, before and after introduction of an opioid-sparing multimodal regimen protocol advocating for standing ibuprofen and acetaminophen. Demographic information, opioid prescription details (oral morphine equivalent [OME]), and refill rate data were collected from the chart. Postoperative opioid use and satisfaction score (for the after group using Likert scale) was obtained by telephone survey. t Test was used to compare continuous variables, and χ2/Fischer exact test was used to compare categorical variables. RESULTS Two hundred ninety-two patients were eligible and contacted. One hundred one patients responded before protocol implementation and 102 responded after protocol implementation. The median number of tablets prescribed was 14.5 (108.5 OME; IQR, 10) and 10 (75 OME; IQR, 5; P < 0.01) preprotocol and postprotocol, whereas the mean number of tablets used was 10 (75 OME; IQR, 13) and 3 (22.5 OME; IQR, 10; P = 0.0009) preprotocol and postprotocol, respectively. Refill rate did not differ significantly (11% preprotocol vs 7% postprotocol P = 0.32) Mean satisfaction score was 4.3 (SD, 0.9). CONCLUSIONS A multimodal analgesia regimen limiting postoperative opioids decreased postoperative opioid prescribing and consumption while maintaining similar patient satisfaction and refill rates.

Objectives This study aimed to identify differences in severity of overactive bladder (OAB) symptoms in women of different races and ethnicities using urodynamic study (UDS) parameters. Methods We performed a 5-year retrospective chart review from January 2014 to January 2019 of women 18 years and older who endorsed OAB symptoms and underwent UDS at a racially and ethnically diverse academic urban medical center. Logistic and linear regressions were used to examine the associations of various UDS parameters between racial/ethnic groups, after adjusting for age, diabetes, and parity. Results A total of 161 women with an average age of 59 years were included in the study. The racial/ethnic composition of the group was Hispanic (62%), black (24%), and white (11%). Symptoms on presentation included urgency and/or frequency (11.8%), urge incontinence (23.0%), or mixed urinary symptoms (65.2%). Black and Hispanic women presented with differing symptoms (urgency/frequency vs mixed urinary symptoms). Half of the patients (n = 82) had detrusor overactivity. Compared with whites, blacks were 3.4-fold more likely to have detrusor overactivity (95% confidence interval, 0.99-11.40) and had lower volumes at time of "strong desire" (-102.6 mL, P = 0.003). Hispanics had on average 75.88 mL less volume at sensation of "strong desire" (P = 0.016) than did whites. Conclusions Our study suggests that minority race and ethnicity may be associated with worse performance on certain UDS parameters. Future studies should aim to understand if these differences are due to genetic, disease-related, behavioral, and/or socioeconomic factors and whether these differences are associated with worse subjective OAB.

Background: Several studies have examined association between human papillomaviruses (HPV) and esophageal cancer, but results have been inconsistent. This is the first prospective study to investigate associations between α, β and γ HPV detection in the oral cavity and risk of esophageal cancer. Methods: We conducted a nested case–control study among 96,650 cancer-free participants in the American Cancer Society Cancer Prevention Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Incident esophageal cancer cases (n = 125) were identified during an average 3.9 years of follow-up. Three controls per case (n = 372) were selected and matched on age, sex, race/ethnicity, and time since mouthwash collection. α, β, and γ HPV DNA in oral samples were detected using a next-generation sequencing assay. Conditional logistic regression models were used to estimate OR and 95% confidence intervals (CIs), adjusting for smoking and alcohol consumption. Statistical significance was evaluated using permutation test. Results: Prevalence of oral α, β, and γ HPV was 18.4%, 64.8%, and 42.4% in cases and 14.3%, 55.1%, and 33.6% in controls, respectively. Oral HPV16 detection was not associated with esophageal cancer (OR = 0.54, 95% CI, 0.1–4.84) and none of the esophageal squamous cell carcinoma cases (n = 28) were HPV16 positive. Some oral HPV types were more common in cases than controls; however, none of the associations were statistically significant. Conclusions: Although HPVs in the oral cavity are very common, this study showed no evidence of association between oral HPVs and esophageal cancer. Impact: Oral HPVs may not contribute to risk of esophageal cancer. Cancer Epidemiol Biomarkers Prev; 27(10); 1168–75. ©2018 AACR.

Purpose Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Introduction: Obesity and type II diabetes mellitus (T2DM) have been associated with adverse prostate cancer (PrCa) outcomes in several studies; however, results have been inconsistent. We examined the independent and combined effects of body mass index (BMI)/obesity and T2DM in relation to the National Comprehensive Cancer Network (NCCN) PrCa risk groups in a large, racially-diverse patient population from an urban medical center. Methods: We abstracted demographic, clinical and pathological data, as well as BMI/obesity and T2DM status at time of PrCa diagnosis from all patients, who underwent radical prostatectomy for their cancer at our academic institution from 2005 through 2019. Patients were classified into three NCCN PCa risk groups: low, intermediate and high risk based on their pathological Gleason score, tumor stage and diagnostic serum PSA. Multinomial logistic regression models were used to examine associations of obesity (BMI>30kg/m2) and T2DM with risks of intermediate and high risk PCa (comparison group were men with low risk disease). We examined both independent and combined effects of obesity and T2DM in multivariate models adjusted for age and race/ethnicity (main effect models were also adjusted for BMI or T2DM). Results: A total 1,366 PrCa patients with an average age of 60±6.9 years old with complete data were included in this analysis. The majority of patients were African-American (37.2%) or Hispanic (31.5%). The prevalence of obesity and T2DM were 29.4% and 28% respectively in this cohort, with African-Americans having the highest prevalence of both obesity (38.1%) and T2DM (43.6%) compared to other races/ethnicities. A large proportion of patients had NCCN intermediate (64%) or high-risk (14%) disease. In multivariate analyses, obesity was associated with 2.23 increased odds of high-risk PCa (95%CI: 1.26-3.93), while T2DM was associated with OR=1.53 (95%CI: 1.08-2.17) of intermediate risk PCa. Interaction analysis showed that obese patients with T2DM had increased risks of both intermediate (OR=1.99; 95%CI 1.16-3.41) and high-risk PCa (OR=2.28; 95%CI 1.14-4.53) when compared to lean men without T2DM. Discussion: In this multiracial population, both obesity and T2DM were independently associated with high risk PrCa. Moreover, there was an additive effect of obesity and T2DM in the odds of developing both intermediate and high risk PrCa. Potential biological pathways of insulin signaling and inflammatory factors arising from adipokines could be involved in promoting more aggressive PrCa phenotypes. Larger cohort studies are needed to better elucidate the mechanisms between T2DM, obesity, and PrCa tumor pathology. Citation Format: Michelle Toker, Denzel Zhu, William Shyr, Ethan Fram, Kara L. Watts, Ilir Agalliu. Association of obesity and diabetes with prostate cancer risk group in a multiethnic population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB087.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. Significance: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

Background Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. Patients and methods We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6–11 years, range = 0–40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). Results HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1–155.4) in whites and 17.2-fold (95% CI 1.7–170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time 30 years (N = 24), 20–30 years (N = 148), 10–20 years (N = 228), and