Trends in prostate cancer incidence among Black men in the Caribbean and the United States.

BACKGROUND: Prostate cancer incidence is highest for Black men of the African diaspora in the United States and Caribbean. Recent changes in recommendations for prostate cancer screening have been shown to decrease overall prostate cancer incidence and increase the likelihood of late stage disease. However, it is unclear how trends in prostate cancer characteristics among high risk Black men differ by geographic region during the changes in screening recommendations. METHODS: In this study, we used population-based prostate cancer registry data to describe age-adjusted prostate cancer incidence trends from 2008 to 2015 among Black men from six geographic regions. We obtained data on incident Black prostate cancer patients from six cancer registries (in the United States: Florida, Alabama, Pennsylvania, and New York; and in the Caribbean: Guadeloupe and Martinique). After age standardization, we used descriptive analyses to compare the demographics and tumor characteristics by cancer registry site. The Joinpoint regression program was used to compare the trends in incidence by site. RESULTS: A total of 59,246 men were analyzed. We found the highest incidence rates (per 100,000) for prostate cancer in the Caribbean countries (181.99 in Martinique and 176.62 in Guadeloupe) and New York state (178.74). Incidence trends decreased significantly over time at all sites except Martinique, which also showed significantly increasing rates of late stage (III/IV) and Gleason score 7+ tumors. CONCLUSIONS: We observed significant differences in prostate cancer incidence trends among Black men after major changes prostate screening recommendations. Future studies will examine the factors that differentially influence prostate cancer trends among the African diaspora.

Ambient air exposures to arsenic and cadmium and overall and prostate cancer-specific survival among prostate cancer cases in Pennsylvania, 2004 to 2014.

BACKGROUND: Exposures to arsenic (As) and cadmium (Cd) have been associated with higher prostate cancer (PC) mortality; however, these associations have been inconsistent. The authors investigated whether higher ambient air concentrations of As and Cd are associated with lower overall and PC-specific survival among PC cases in Pennsylvania. METHODS: Incident PC cases of patients, aged 40 years or older, with a clinical diagnosis and nonmetastatic disease were identified in the 2004 to 2014 Pennsylvania Cancer Registry. Demographic, clinical, and pathologic information were extracted from the Pennsylvania Cancer Registry. The 3- and 5-year average and cumulative air concentrations of As and Cd were extracted from the Environmental Protection Agency's Toxics Release Inventory database. Spatial-temporal hierarchical accelerated failure time models were used to examine the associations between air concentrations of As and Cd and overall and PC-specific survival for the total population and stratified by geographical region defined by rurality and Appalachia status, after adjusting for confounders. RESULTS: There were 78,914 PC cases included. Increasing 3- and 5-year average and cumulative air concentrations of As and Cd were significantly associated with lower overall and PC-specific survival among cases, after adjusting for confounders, for the total population, and stratified by geographical region for most of the estimates. CONCLUSIONS: Data suggest that increasing ambient air exposures to As and Cd may play a role in overall and PC-specific mortality risk among PC cases. Exposures to As and Cd are modifiable and may provide insight into potential strategies to improve PC health outcomes. LAY SUMMARY: Arsenic and cadmium exposures linked to increased prostate cancer deaths remain unclear. We investigated whether air levels of arsenic and cadmium reported to be released from industries decrease overall and prostate cancer-specific survival among prostate cancer cases identified in the 2004 to 2014 Pennsylvania Cancer Registry. Among the 78,914 prostate cancer cases, increasing air levels of arsenic and cadmium are found to be associated with lower overall and prostate cancer-specific survival for the total population and within rural and urban Appalachia and urban non-Appalachia counties in Pennsylvania. Reducing exposures to arsenic and cadmium have the potential to decrease prostate cancer deaths.

Temporal and spatial trends and determinants of aggressive prostate cancer among Black and White men with prostate cancer.

PURPOSE: Few studies have reported temporal and spatial trends of aggressive prostate cancer (PC) among black men who are known to have more aggressive disease. We examined these trends for highly aggressive PC at diagnosis among black and white men in Pennsylvania (PA). METHODS: Men, aged ≥ 40 years, with a primary, clinical PC diagnosis were identified from the Pennsylvania Cancer Registry, 2004-2014. Joinpoint analysis was used to evaluate the temporal trend of highly aggressive PC (clinical/pathologic Gleason score ≥ 7 [4 + 3], clinical/pathologic tumor stage ≥ T3, or distant metastasis) and identify change points by race in which annual percent change (APC) was calculated. Logistic regression analyses were used to examine the association between race and highly aggressive PC, after adjusting for covariates with and without spatial dependence. RESULTS: There were 89,133 PC cases, which included 88.7% white and 11.3% black men. The APC of highly aggressive PC was 8.7% from 2011 to 2014 among white men and 3.6% from 2007 to 2014 among black men (p values ≤ 0.01). The greatest odds of having highly aggressive PC among black compared to white men were found in counties where the black male population was ≤ 5.3%. CONCLUSIONS: Highly aggressive PC increased for both black and white men in PA between 2004 and 2014. Black men had more aggressive disease, with the greatest odds in counties where the black male population was small. The increase in highly aggressive PC may be due to less screening for PC, resulting in more advanced disease at diagnosis.

Spatial patterns in prostate Cancer-specific mortality in Pennsylvania using Pennsylvania Cancer registry data, 2004-2014.

BACKGROUND: Spatial heterogeneity of prostate cancer-specific mortality in Pennsylvania remains unclear. We utilized advanced geospatial survival regressions to examine spatial variation of prostate cancer-specific mortality in PA and evaluate potential effects of individual- and county-level risk factors. METHODS: Prostate cancer cases, aged ≥40 years, were identified in the 2004-2014 Pennsylvania Cancer Registry. The 2018 County Health Rankings data and the 2014 U.S. Environmental Protection Agency's Environmental Quality Index were used to extract county-level data. The accelerated failure time models with spatial frailties for geographical correlations were used to assess prostate cancer-specific mortality rates for Pennsylvania and by the Penn State Cancer Institute (PSCI) 28-county catchment area. Secondary assessment based on estimated spatial frailties was conducted to identify potential health and environmental risk factors for mortality. RESULTS: There were 94,274 cases included. The 5-year survival rate in PA was 82% (95% confidence interval, CI: 81.1-82.8%), with the catchment area having a lower survival rate 81% (95% CI: 79.5-82.6%) compared to the non-catchment area rate of 82.3% (95% CI: 81.4-83.2%). Black men, uninsured, more aggressive prostate cancer, rural and urban Appalachia, positive lymph nodes, and no definitive treatment were associated with lower survival. Several county-level health (i.e., poor physical activity) and environmental factors in air and land (i.e., defoliate chemical applied) were associated with higher mortality rates. CONCLUSIONS: Spatial variations in prostate cancer-specific mortality rates exist in Pennsylvania with a higher risk in the PSCI's catchment area, in particular, rural-Appalachia. County-level health and environmental factors may contribute to spatial heterogeneity in prostate cancer-specific mortality.

Circulating microRNAs in plasma among men with low-grade and high-grade prostate cancer at prostate biopsy.

BACKGROUND: MicroRNAs (miRNAs or miR-) have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence and metastasis. We investigated whether circulating miRNAs in plasma could be used as diagnostic biomarkers for more aggressive prostate cancer at prostate biopsy. METHODS: Men, aged 40 years and above, newly diagnosed with prostate cancer were categorized into two risk groups, low-grade (Gleason score, 6 or 7 [3 + 4] and serum prostate-specific antigen [PSA], <20 ng/mL) and high-grade (Gleason score, ≥7 (4 + 3) and serum PSA, ≥20 ng/mL) prostate cancers. The limma R package was used to compare the expression of miRNAs in plasma between the two risk groups, adjusting for age. RESULTS: There were 66 men, aged 46-86 years, included: 40 men with low-grade and 26 men with high-grade prostate cancers. There were lower expressions of miR-28, miR-100, miR-942, and miR-28-3p, and higher expressions of miR-708, miR-1298, miR-886-3p, miR-374, miR-376c, miR-202, miR-128a, and miR-185 in high-grade compared to low-grade prostate cancer cases at biopsy, after adjusting for age (P < 0.05). These differences were no longer statistically significant after adjusting the P values for multiple comparisons. CONCLUSION: There was no circulating miRNA associated with high-grade prostate cancer at biopsy after adjusting for age and multiple comparisons. Nevertheless, relationships between these circulating miRNAs and high-grade prostate cancer were observed, which suggest them as promising prostate cancer biomarkers. Further investigation in a larger cohort may provide insight into their diagnostic potential for aggressive prostate cancer.

Circulating microRNAs in plasma as potential biomarkers for the early detection of prostate cancer.

BACKGROUND: MicroRNAs (miRNAs) have been linked to prostate cancer (PC) risk; however, their role as a screening biomarker for PC has yet to be determined. We examined whether circulating miRNAs in plasma could be potential biomarkers for the early detection of PC among men undergoing prostate needle biopsy. METHODS: Men who had a prostate biopsy due to an abnormal screening test were recruited. Linear regression was used to examine the association between miRNAs in plasma and PC status and to model individual miRNA expression on serum PSA and age to calculate the partial correlation coefficient (r). RESULTS: There were 134 men, aged 46-86 years, included, with 66 men with a PC diagnosis (cases), eight men with no PC diagnosis but atypical lesion, and 60 men without a PC diagnosis (controls). The most statistically significant PC circulating miRNAs were miR-381, miR-34a, miR-523, miR-365, miR-122, miR-375, miR-1255b, miR-34b, miR-450b-5p, and miR-639 after adjusting for age (P-values ≤0.05); however, they were no longer statistically significant after P-value adjustment for multiple comparisons. MiR-671-3p was differentially expressed between black and white cases (P-value = 0.03). Moderate positive correlations with serum PSA were observed for miR-381 overall and among controls (r = 0.43-0.60; P-values ≤0.05) and miR-34a among cases (r = 0.46; P-value = 0.02). CONCLUSIONS: There was no miRNA associated with PC diagnosis after adjusting for age and P-values; however, moderate correlations between miRNAs and serum PSA were observed. Further investigation between miRNAs and PC risk is warranted in a larger population at high risk for PC.

Serum carotenoid and retinol levels in African-Caribbean Tobagonian men with high prostate cancer risk in comparison with African-American men.

Black men are known to have a higher risk for prostate cancer (PC). Carotenoids and retinol, linked to PC, have not been compared in different black populations at risk. We examined serum carotenoid and retinol levels between PC-free African-Caribbean (AC) Tobagonian men with a high PC risk (high-grade prostatic intraepithelial neoplasia, atypical foci or repeated abnormal PC screenings) and African-American (AA) men with elevated serum prostate-specific antigen (PSA) levels (≥4 ng/ml). AC men who participated in the 2003 lycopene clinical trial and AA men who participated in the 2001-2006 National Health and Nutrition Examination Survey were compared. Serum specimens were analysed for carotenoid (ß-carotene, α-carotene, ß-cryptoxanthin, lutein/zeaxanthin and lycopene) and retinol levels by isocratic HPLC. Quantile regression was used to examine the association between serum carotenoid and retinol levels and black ethnicity, overall and among men with elevated serum PSA. There were sixty-nine AC men and sixty-five AA men, aged 41-79 years, included. AC men were associated with lower serum lycopene and retinol levels, and higher serum α- and ß-carotenes and lutein/zeaxanthin levels compared with AA men, after adjusting for age, BMI, ever smoked cigarettes, education and hypertension (P≤0·03). Among men with elevated PSA, serum retinol was no longer statistically significant with ethnicity (P=0·06). Possible differences may be attributed to dietary intake, genetics and/or factors that influence bioavailability of these micronutrients. Prospective studies are warranted that investigate whether these differences in micronutrients between AC Tobagonian and AA men influence PC risk.

Human herpesvirus 8 seroconversion in a population-based cohort of men in Tobago.

Human herpesvirus 8 (HHV-8) is the causal agent of Kaposi's sarcoma (KS). In Tobago, KS is not common; however, HHV-8 seropositivity has been reported to be 39.9% in men with prostate cancer compared to <22.9% in healthier women and men. To understand HHV-8 transmission, we examined HHV-8 seroconversion and seroreversion, and risk factors for these changes in Tobago men. Serum specimens from a sub-cohort of Tobago Prostate Survey men, aged 40-81 years (n = 381/442), were collected at baseline and a subsequent visit between 3 and 9 years and tested for HHV-8 seropositivity using an immunofluorescence assay for antibodies against HHV-8 lytic antigens. Poisson distribution was used to calculate HHV-8 seroconversion and seroreversion rates and their 95% confidence intervals. Differences in baseline characteristics between HHV-seroconverters versus persistent HHV-8 seronegative men and HHV-8 seroreverters versus HHV-8 seropositive men were examined. HHV-8 seropositivity was 12.3% (N = 381) at baseline, with HHV-8 seropositivity significantly higher in increasing age groups, 40-49 (4.0%) to 70-81 (37.5%) years (P-value trend <0.0001). HHV-8 seroconversion and seroreversion rates were 0.23 per 100 person-years (95% C.I., 0.06-0.58) and 2.42 per 100 person-years (95% C.I., 0.89-5.26), respectively. There were significantly more HHV-8 seroconverters who reported "ever smoked cigarettes of >6 months" at baseline compared to HHV-8 persistent seronegative men (P-value = 0.03). Baseline characteristics of HHV-8 seroreverters did not differ from persistent seropositive men. Low HHV-8 seroconversion and seroreversion rates were found. Data suggest that HHV-8 transmission occurred at earlier ages, <40 years, in Tobago men.

Association between systemic inflammatory markers and serum prostate-specific antigen in men without prostatic disease - the 2001-2008 National Health and Nutrition Examination Survey.

BACKGROUND: Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer. METHODS: We investigated the associations between systemic inflammatory markers and serum PSA in 3,164 healthy men without prostatic disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C-reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count, and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as levels equal or greater than 4 ng/ml. RESULTS: Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv = 1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv = 1.14; 95% CI, 1.03-1.26), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications. CONCLUSIONS: Markers of systemic inflammation were associated with elevated PSA in men without known prostatic disease. Future studies are needed to examine these markers' relationship with prostate cancer occurrence and progression.

Genetic Factors Associated with Absolute and Relative Plasma Concentrations of Calcitriol.

BACKGROUND: Little is known regarding factors associated with calcitriol and a relative measure of calcitriol, the calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR). METHODS: Using a cross-sectional study design, healthy young adults of African and European descent, matched (1:1) on age (±5 years) provided a blood sample in non-summer months (N = 376). Vitamin D metabolites were measured in plasma with HPLC/MS-MS. West African genetic ancestry proportion (WGA) was estimated using STRUCTURE modeling of genetic ancestry-informative markers. Multivariable regression models were used to estimate the association of WGA and vitamin D-pathway gene variants with calcitriol and C24CPR, controlling for days from summer solstice, age, sex, blood pressure, body mass index, dietary vitamin D intake, oral contraceptive/medroxyprogesterone acetate use, smoking, tanning bed use, and time of day. RESULTS: Calcitriol and C24CPR were not highly correlated (rho = 0.14), although both were significantly, positively, and monotonically associated with WGA (Ptrend 0.025 and <0.001, respectively). In fully adjusted models, genetic factors explained a greater proportion of variability in C24CPR (R2 = 0.121 and 0.310, respectively). Variants in genes with associated with calcitriol (CALB1, CYP27B1, GC, and PPARGC1A) differed from those associated with C24CPR (CYP3A43, FGF23, KL, and VDR). CONCLUSIONS: Both absolute and relative measures of calcitriol were significantly higher among African Americans. Otherwise, these biomarkers appear to be genetically distinct. IMPACT: C24CPR may be better suited to personalized medicine, due to a higher proportion of population variability explained by genetic variation and a less skewed distribution.

Evaluation and Comparison of Real-World Databases for Conducting Research in Patients With Colorectal Cancer.

PURPOSE: Evaluating whether patient populations in clinico-genomic oncology databases are comparable with whom in other databases without genomic component is important. METHODS: Four databases were compared for colorectal cancer (CRC) cases and stage IV CRC cases: American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC), The Cancer Genome Atlas (TCGA), SEER-Medicare, and MarketScan Commercial and Medicare Supplemental claims databases. These databases were also compared with the SEER registry database which serves as national benchmarks. Demographics, clinical characteristics, and overall survival were compared in patients with newly diagnosed CRC and patients with stage IV CRC across databases. Treatment patterns were further compared in patients with stage IV CRC. RESULTS: A total of 65,976 patients with CRC and 13,985 patients with stage IV CRC were identified. GENIE-BPC had the youngest patient population (mean age [years]: CRC, 54.1; stage IV CRC, 52.7). SEER-Medicare had the oldest patient population (CRC, 77.7; stage IV CRC, 77.3). Most patients were male and of White race across databases. GENIE-BPC had the highest proportion of patients with stage IV CRC (48.4% v other databases 13.8%-25.4%) and patients receiving treatments (95.7% v 37.6%-59.1%). Infusional fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab was the most common regimen across databases accounting for 47.3%-78.5% of patients receiving first line of therapy. The median survival from diagnosis was 36, 94, 44 months (CRC) and 23, 36, 15 months (stage IV CRC) for patients in GENIE-BPC after left truncation, TCGA, and SEER-Medicare databases, respectively. CONCLUSION: Compared with other databases, GENIE-BPC had the youngest patients with CRC with the most advanced disease and the largest proportion of patients receiving treatment. Investigators should consider adjustments when extrapolating results from clinico-genomic databases to the general CRC population.

Arsenic exposures and prostate cancer risk: A multilevel meta-analysis.

OBJECTIVE: Previous studies found that arsenic exposures have been linked to prostate cancer risk. However, this finding has been inconsistent. The purpose of this paper was to estimate the effects of arsenic exposures on prostate cancer risk. METHOD: We conducted a meta-analysis of epidemiologic studies of arsenic exposures and prostate cancer risk. We searched for both arsenic exposure and prostate cancer studies published until January 2021 from the following electronic databases: PubMed, Scopus, and Web of Science. Multilevel meta-analysis via random-effects modeling was used to examine the association between arsenic exposures and prostate cancer risk. RESULTS: There were 12 studies included with an effect size of 23. Arsenic exposure was determined from water and soil (n = 8), urinary measurements (n = 2), or self-reported questionnaire (n = 2). Overall, arsenic exposure was found to be statistically significantly associated with prostate cancer risk (Relative risk [RR] = 1.18, 95% confidence interval [CI]: 1.06 - 1.30). In the sub-analysis, arsenic exposure from water and soil was found to be statistically significantly associated with prostate cancer risk (RR= 1.22, 95% CI: 1.05 - 1.41). CONCLUSION: Data suggest that arsenic exposures may play a role in increasing prostate cancer risk. Further prospective studies are warranted to verify the association between arsenic exposure and prostate cancer risk.

Association between urinary arsenic, blood cadmium, blood lead, and blood mercury levels and serum prostate-specific antigen in a population-based cohort of men in the United States.

Exposures to heavy metals have been linked to prostate cancer risk. The relationship of these exposures with serum prostate-specific antigen (PSA), a marker used for prostate cancer screening, is unknown. We examined whether total urinary arsenic, urinary dimethylarsonic acid, blood cadmium, blood lead, and total blood mercury levels are associated with elevated PSA among presumably healthy U.S. men. Prostate cancer-free men, aged ≥40 years, were identified from the 2003-2010 National Health and Nutrition Examination Survey. Logistic regression analyses with survey sample weights were used to examine the association between heavy metal levels and elevated PSA for the total population and stratified by black and white race, after adjusting for confounders. There were 5,477 men included. Approximately 7% had elevated PSA. Men with an elevated PSA had statistically significantly higher levels of blood cadmium and blood lead compared to men with a normal PSA (p-values ≤ 0.02), with black men having higher levels. After adjusting for age, race/ethnicity, body mass index, smoking, and education, there was no association found between any of the heavy metal levels and elevated PSA for the total population. In addition, there was no association found when stratified by black and white race. Further investigation is warranted in a larger cohort of men who persistently are exposed to these heavy metals.

Prostate cancer in Pennsylvania: The role of older age at diagnosis, aggressiveness, and environmental risk factors on treatment and mortality using data from the Pennsylvania Cancer Registry.

BACKGROUND: To assess: (a) cancer treatment in prostate cancer survivors (PCS) by age at diagnosis (ADx) and prostate cancer (PC) aggressiveness; (b) potential impact on PC mortality; and (c) these results in the context of environmental/behavioral risk factors on PCS in Pennsylvania. METHODS: Prostate cancer survivors ages ≥40 years were identified from the 2004-2014 Pennsylvania Cancer Registry (PCR). Demographic/clinical descriptors and PC treatment were extracted from PCR. Prostate cancer aggressiveness was defined by clinical/pathologic Gleason score and tumor stage. Logistic and Cox regression analyses tested associations between treatment received and PC-specific mortality. County-level data from the Pennsylvania BRFSS were used to estimate cancer-related behavioral risk factors (eg, smoking, physical inactivity, fruit/vegetable consumption [FV], alcohol use) and used as covariates. RESULTS: There were 90 694 PCS ages 40-105 years (mean age = 66.19 years, SD = 9.25) included. Most were non-Hispanic white men (83%). Prostate cancer survivors ≥75 years were least likely to receive any treatment but men ages 65-74 were more likely to receive combined therapies (OR = 1.47; 95% CI 1.28, 1.69) vs PCS ages 40-54 years, controlling for covariates. Prostate cancer survivors 55-75+ with aggressive PC who received any treatment vs no definitive treatment had significantly reduced mortality. Men from counties with high obesity and smoking rates were significantly less likely to receive any treatment than men living in counties with lower rates of these risk factors. Prostate cancer survivors who lived in counties with high rates of physical inactivity and had high rates of sufficient FV consumption were slightly more likely to receive cancer treatment vs no definitive treatment compared to men who lived in counties with high rates of physical activity and lower FV consumption. CONCLUSIONS: We observed a general age-related decline in receipt of treatment. Prostate cancer survivors ages ≥75 years were significantly less likely to get any cancer treatment compared to younger PCS. However, most men with more aggressive disease who received any treatment had greatly reduced PC mortality, regardless of age. Considering environmental/behavioral risk factors may attenuate PC risk and inform treatment options.

Prostate Cancer Incidence and Aggressiveness in Appalachia versus Non-Appalachia Populations in Pennsylvania by Urban-Rural Regions, 2004-2014.

BACKGROUND: Few studies have examined prostate cancer incidence and aggressiveness in urban-rural Appalachian populations. We examined these rates in urban-rural Appalachia and non-Appalachia Pennsylvania (PA), and the association between these areas and more aggressive prostate cancer at diagnosis. METHODS: Men, ages ≥ 40 years with a primary prostate cancer diagnosis, were identified from the 2004-2014 Pennsylvania Cancer Registry. Age-adjusted incidence rates for prostate cancer and more aggressive prostate cancer at diagnosis were calculated by urban-rural Appalachia status. Multivariable Poisson regressions were conducted. Multiple logistic regressions were used to examine the association between the geographic areas and more aggressive prostate cancer, after adjusting for confounders. RESULTS: There were 94,274 cases, ages 40-105 years, included. Urban non-Appalachia had the highest 2004-2014 age-adjusted incidence rates of prostate cancer and more aggressive prostate cancer (293.56 and 96.39 per 100,000 men, respectively) and rural Appalachia had the lowest rates (256.48 and 80.18 per 100,000 men, respectively). Among the cases, urban Appalachia were more likely [OR = 1.12; 95% confidence interval (CI) = 1.08-1.17] and rural Appalachia were less likely (OR = 0.92; 95% CI = 0.87-0.97) to have more aggressive prostate cancer at diagnosis compared with urban non-Appalachia. CONCLUSIONS: Lower incidence rates and the proportion of aggressive disease in rural Appalachia may be due to lower prostate cancer screening rates. More aggressive prostate cancer at diagnosis among the cases in urban Appalachia may be due to exposures that are prevalent in the region. IMPACT: Identifying geographic prostate cancer disparities will provide information to design programs aimed at reducing risk and closing the disparity gap.

Human herpesvirus 8 seroprevalence among Tobago women and the role of sexual lifestyle behavior.

Human herpesvirus 8 (HHV-8) infection is present in 22.9% of Tobago men. However, seroprevalence and modes of transmission of HHV-8 among Tobago women are not known. HHV-8 seropositivity rates in Tobago women were examined and compared rates to Tobago men of similar ages. To assess possible modes of transmission, sexual behavior among Tobago women was examined to determine its association with HHV-8 seropositivity. A cross-sectional study was conducted in 213 Tobago women, ages 18-65 years, who participated in the Tobago Cervical and Oral Cancer Screening Study. HHV-8 seropositivity was determined by a monoclonal immunofluorescence assay. Age-specific rates were compared to those previously observed in men. Logistic regression analyses were performed to determine the association between HHV-8 seropositivity and sexual behavior among the women. HHV-8 seroprevalence among Tobago women was 14.1% (95% CI, 10-19%), with no significant difference with men of similar age (P-value = 0.741). Age

Circulating microRNAs in plasma before and after radical prostatectomy.

PURPOSE: MicroRNAs (miRNAs/miRs) as circulating biomarkers for prostate cancer have yet to be determined. We examined whether circulating miRNAs in plasma could be employed as biomarkers of disease among men treated for prostate cancer by radical prostatectomy (RP). METHODS: The expression of 17 preselected circulating miRNAs associated with prostate cancer (miR-381, -34a, -365, -122, -375, -1255b, -34b, -450b-5p, -885-5p, -1260, -150, -378, -671-3p, -148a, and -224) or high-grade prostate cancer (miR-28 and -100) in plasma at prostate biopsy was examined in pre- and post-RP plasma of prostate cancer patients using real-time PCR and compared using Wilcoxon signed-ranked test. Wilcoxon rank sum test was used to compare the expression of miRNAs in pre-RP plasma between pathologic tumor stage (T2 vs. T3) and Gleason score (6-7 [3 + 4] vs. ≥ 7 [4 + 3]) groups. Partial correlation coefficient between the expression of miRNAs in pre-RP plasma and serum prostate-specific antigen (PSA) level at RP, adjusting for age, was calculated. RESULTS: Twenty-nine men, aged 43 to 77 years, were included. Median follow-up time after RP was 55 days. There was no significant change in the expression of miRNAs in plasma from before to after RP. However, higher expression of miR-34a, -378, and 450b-5p in pre-RP plasma was observed among T3 compared to T2 patients (P values = 0.01). Overall, there were no statistically significant relationships observed between the expression of these circulating miRNAs and Gleason score and serum PSA at RP. CONCLUSIONS: There was no significant change in the expression of circulating miRNAs in plasma from before to approximately 2 months after RP. This finding may be due to the lack of immediate effect RP may have on the expression of circulating miRNAs. However, higher expression of miR-34a, -378, and -450b-5p in plasma was found among patients with more advanced disease at RP. A longer follow-up time after RP is warranted to investigate RP's possible influence on circulating miRNAs among men treated for prostate cancer and to evaluate miRNAs' diagnostic potential for prostate cancer.

Regional, racial, gender, and tumor biology disparities in breast cancer survival rates in Africa: A systematic review and meta-analysis.

BACKGROUND: The survival rates from breast cancer in Africa are poor and yet the incidence rates are on the rise. In this study, we hypothesized that, in Africa, a continent with great disparities in socio-economic status, race, tumor biology, and cultural characteristics, the survival rates from breast cancer vary greatly based on region, tumor biology (hormone receptor), gender, and race. We aimed to conduct the first comprehensive systematic review and meta-analysis on region, gender, tumor-biology and race-specific 5-year breast cancer survival rates in Africa and compared them to 20-year survival trends in the United States. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library to identify studies on breast cancer survival in African published before October 17, 2018. Pooled 5-year survival rates of breast cancer were estimated by random-effects models. We explored sources of heterogeneity through subgroup meta-analyses and meta-regression. Results were reported as absolute difference (AD) in percentages. We compared the survival rates of breast cancer in Africa and the United States. FINDINGS: There were 54 studies included, consisting of 18,970 breast cancer cases. There was substantial heterogeneity in the survival rates (mean 52.9%, range 7-91%, I2 = 99.1%; p for heterogeneity <0.0001). Meta-regression analyses suggested that age and gender-adjusted 5-year survival rates were lower in sub-Saharan Africa compared to north Africa (AD: -25.4%; 95% CI: -34.9 - -15.82%), and in predominantly black populations compared to predominantly non-black populations (AD: -25.9%; 95% CI: 35.40 - -16.43%). Survival rates were 10 percentage points higher in the female population compared to male, but the difference was not significant. Progesterone and estrogen receptor-positive breast cancer subtypes were positively associated with survival (r = 0.39, p = 0.08 and r = 0.24, p = 0.29 respectively), but triple-negative breast cancer was negatively associated with survival. Survival rates are increasing over time more in non-black Africans (55% in 2000 versus 65% in 2018) compared to black Africans (33% in 2000 versus 40% in 2018); but, the survival rates for Africans are still significantly lower when compared to black (76% in 2015) and white (90% in 2015) populations in the United States. CONCLUSION: Regional, sub-regional, gender, and racial disparities exist, influencing the survival rates of breast cancer in Africa. Therefore, region and race-specific public health interventions coupled with prospective genetic studies are urgently needed to improve breast cancer survival in this region.

Distribution of Human Papillomavirus Genotypes among HIV-Positive and HIV-Negative Women in Cape Town, South Africa.

OBJECTIVE: HIV-positive women are known to be at high-risk of human papillomavirus (HPV) infection and its associated cervical pathology. Here, we describe the prevalence and distribution of HPV genotypes among HIV-positive and -negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN). METHODS: We report data on 1,371 HIV-positive women and 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies in Cape Town, South Africa, conducted among women who had no history of cervical cancer screening recruited from the general population. All women were tested for HIV. Cervical samples were tested for high-risk HPV DNA (Hybrid Capture 2) with positive samples tested to determine the specific genotype (Line Blot). CIN status was determined based on colposcopy and biopsy. RESULTS: The HPV prevalence was higher among HIV-positive women (52.4%) than among HIV-negative women (20.8%) overall and in all age groups. Younger women, aged 17-19 years, had the highest HPV prevalence regardless of HIV status. HIV-positive women were more likely to have CIN 2 or 3 than HIV-negative women. HPV 16, 35, and 58 were the most common high-risk HPV types with no major differences in the type distribution by HIV status. HPV 18 was more common in older HIV-positive women (40-65 years) with no or low grade disease, but less common in younger women (17-29 years) with CIN 2 or 3 compared to HIV-negative counterparts (p < 0.03). Infections with multiple high-risk HPV types were more common in HIV-positive than HIV-negative women, controlling for age and cervical disease status. CONCLUSION: HIV-positive women were more likely to have high-risk HPV than HIV-negative women; but, among those with HPV, the distribution of HPV types was similar by HIV status. Screening strategies incorporating HPV genotyping and vaccination should be effective in preventing cervical cancer in both HIV-positive and -negative women living in sub-Saharan Africa.

Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

OBJECTIVE: Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN). METHODS: We report data on 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status. RESULTS: Overall, 20.7% (95% CI, 19.9-21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17-29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40-65 years). CONCLUSION: HPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.