A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men.

BACKGROUND: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. METHODS: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA < 2.5 ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS ≤ 7[3 + 4]), TS ≤ pT2) and high risk (GS≥ 7[4 + 3], TS > pT2) PCa. Statistical analyses were done using SAS. RESULTS: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P < 0.0001) and PR (P = 0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P = 0.034). CONCLUSION: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

Association of serum lipid levels and prostate cancer severity among Hispanic Puerto Rican men.

BACKGROUND: While obesity and fat intake have been associated with an increased risk of prostate cancer (PCa) aggressiveness and mortality, the association between lipid levels and PCa phenotype remains unclear. Previous reports evaluating this association are inconsistent and highly variable when considering different racial/ethnic groups. There are scarce data regarding this association among Hispanics, and specifically Puerto Rico's Hispanic men, a population with a higher burden of PCa, metabolic syndrome and overweight. This population has a different ancestry profile than other Hispanics from Central and South America. Due to the above the researchers inquired if there is a relationship between serum lipid levels and PCa phenotype in this understudied population using a cohort of patients treated with radical prostatectomy as their first treatment. METHODS: We performed an exploratory retrospective medical record review study of 199 PCa patients who underwent radical prostatectomy between 2005 and 2012. Variables analyzed included age at PCa diagnosis, Body Mass Index (BMI), preoperative serum prostate-specific antigen (PSA), lipid levels, and clinical parameters such as prostatectomy pathologic stage and Gleason Score (GS). PCa severity was defined using pathologic stage and GS. Unadjusted and adjusted logistic regression models were fitted to estimate the odds ratios (ORs) with 95 % confidence intervals (CI) to define the relationship among clinical characteristics and PCa severity. RESULTS: Mean age for the cohort was 58.8 years (range: 40-75), 78.9 % were overweight or obese, 36.7 % had hypertriglyceridemia, and 35.2 % had low HDL levels. In the unadjusted logistic regression model, hypertriglyceridemia (OR: 2.11, 95 % CI = 1.13-3.93), low HDL (OR: 1.90, 95 % CI = 1.02-3.56-), and age (OR: 2.34, 95 % CI 1.25-4.40) were significantly associated with a diagnosis of high severity of PCa. CONCLUSIONS: In Puerto Rican men with PCa, elevated hypertriglyceridemia, low HDL levels, and age were statistically associated with high grade PCa on bivariate analysis. Total cholesterol level was not associated with severity of disease. Associations lost significance upon multivariate adjustment. These data generate important hypotheses regarding the potential relationship between lipid pathways and PCa development and underscore the need to perform larger scale and longitudinal studies to sort out whether, hypertriglyceridemia is associated with PCa phenotype and development.

Body mass index affects the diagnosis and progression of prostate cancer in Hispanics.

INTRODUCTION: The occurrence of lower prostate-specific antigen (PSA) levels in overweight White and African American men has been studied, but there is no data regarding Hispanics, which have a higher mortality rate from Prostate Cancer (PCa) than Whites. The objective of this study was to investigate if being overweight could affect both the sensitivity of the PSA as a diagnostic tool and the progression of PCa in this group. METHODS: Retrospective study of records from 400 patients that underwent testing for PCa during 2005 and 400 patients under treatment for PCa from 2003-2005 at the urology clinics of the Veterans Administration Caribbean Healthcare System. Accrued data included body mass index (BMI), age, PSA levels, biopsy results, and cancer status after treatment. RESULTS: In men, with normal age adjusted PSA levels, overweight and obese men had 35.38% and 38.13%, respectively, positive biopsies while men with normal BMI had 26.15%. In addition, 73.84% of overweight men over 61 years old with normal PSA were positive for prostate cancer. There is a statistically significant decrease in PSA sensitivity from 71.7 (95% CI: 58.6-82.5) in men with normal BMI to 55.4 (95% CI: 41.5-68.7) in obese men (P = .015). In multivariate analysis, patients with a BMI over 25 kg/m2 had a 2.63 (CI 95%: 1.23-5.64) fold higher risk of metastases than those with normal BMI. CONCLUSIONS: in overweight Hispanic men the PSA level is a less sensitive marker for PCa and those individuals with higher BMI have higher prevalence of metastatic disease.

Scientometric analysis of the Puerto Rico Clinical and Translational Research Consortium (PRCTRC) research publications, 2010-2018.

We analyzed the publication productivity supported by the Puerto Rico Consortium for Clinical and Translational Research (PRCTRC) using the structured process of scientometrics. The objective of this study was to evaluate the impact of the research and collaborations as presented in publications. Manuscripts published from 2010 to 2018 and that had the PRCTRC award number and a PMCID number were retrieved from the Science Citation Index database. Scientometric indicators included h-index (HI), average citation (AC), collaboration coefficient (CC), collaboration index (CI), and degree of collaboration (DC) analysis, and relative citation ratio (RCR) was done with Web of Science Platform, iCite, and Stata software. Joinpoint Trend Analysis Software was used to calculate the annual percent change (APC). From 2010 to 2018, 341 publications were identified with an average of 38 publications per year and a total of 3569 citations excluding self-citations. A significant growth (APC: 17.76%, P < 0.05) of scientific production was observed. The overall HI was 31, and the AC per item was 11.04. The overall CC was 0.82, the CI was 8.59, and the DC was 99.1%. This study demonstrates a statistically significant increase in the PRCTRC scientific production. Results allow for the assessment of the progress resulting from the provided support and to plan further strategies accordingly.

Association of thyroid-stimulating hormone levels and body mass index in overweight Hispanics in Puerto Rico.

INTRODUCTION: Obesity is a serious public health problem, and the increasing prevalence of overweight status in the population is a major concern worldwide. Fifty eight percent of the Hispanic population of Puerto Rico is obese, but no data are available regarding thyroid status and body mass index (BMI) in this Hispanic group. This study was conducted to investigate if a relationship existed between obesity and thyroid function, as measured by thyroid-stimulating hormone (TSH) levels on a group of Hispanics enrolled in a weight control clinic in Puerto Rico. METHODS: We conducted a retrospective analysis of 637 clinical files of patients enrolled at Doctors Weight Loss Center. Five hundred seventy-five patients were eligible for this study. Inclusion criteria were adults > or = 21 years of age with data for age, sex, height, weight, percentage fat, and TSH values. RESULTS: Prevalence of subclinical or mild hypothyroidism (TSH > 4.1 mU/L), as per American Thyroid Association definitions, was 8.2% in our study group, which is higher than reported in the National Health and Nutrition Examination Survey (NHANES). Another 18.2% were in the at-risk category (TSH 2.51-4.0 mU/L). CONCLUSION: We found no association between thyroid status and overweight or obesity in this study group but found a higher prevalence of subclinical hypothyroidism compared to the prevalence reported in NHANES.

Cancer of the larynx in Puerto Rico.

INTRODUCTION: Cancer of the larynx is the fourteenth most common cancer in the world. The purpose of this cross-sectional study is to examine the characteristics of laryngeal cancer in Puerto Rico. The study evaluates whether this type of cancer is increasing, to what degree gender differences occur; and describe common types of medical treatment. METHOD: Information on cases of laryngeal cancer for the period of 1997 to 2002 was collected at the Puerto Rico Central Cancer Registry, Department of Health. The incidence of laryngeal cancer in Puerto Rico during the study period was estimated. Sex differences in case-fatality rate and other variables were analyzed. Medical treatments for laryngeal cancer were also analyzed. RESULTS: The study revealed that the average incidence of laryngeal cancer in Puerto Rico was 3.8 x 100,000 from 1997-1998 and 3.5 x 100,000 from 2001-2002 (-1.07 APC). Of all the cases (n = 848) of laryngeal cancer reviewed, 88% were male. Females were more likely to be diagnosed before age 50 than males (p = 0.02). In this study, women had twice the probability of being alive at the end of the study period (OR = 1.97; CI: 1.14-3.45). The two most frequent types of single treatments for laryngeal cancer were radiation (39%) and surgery (33%). CONCLUSIONS: Cases oflaryngeal cancer are decreasing in Puerto Rico. Significant differences by sex were observed, especially the stage of the disease at the time of diagnosis. Future studies on medical treatment modalities that better preserve vocal function concurrently with voice therapy are recommended.

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men.

BACKGROUND: Obesity is prevalent in PR and has been associated with prostate cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim of this work was to ascertain whether the presence of these SNPs is associated with PCa risk and severity in a cohort of Puerto Rican men. METHODS AND FINDINGS: The study population consisted of 513 Puerto Rican men age ranging from 40-79 years old who underwent radical prostatectomy (RP) as the first treatment for PCa and 128 healthy Puerto Rican men age ranging from 40-79 years old. Genomic DNA (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was defined based on RP stage and Gleason Score. The relationship of FTO SNPs with demographic, clinical characteristics, PCa status and PCa severity were assessed. Logistic regression models with a 95% confidence interval (CI) determined SNPs interaction with PCa risk and severity odds ratio (ORs). RESULTS AND DISCUSSION: BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent genotypes and the frequency of alleles and genotypes for both SNPs agreed with those published in 1000 genomes. Results suggest an inverse association between the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31-0.92) and a positive association with overweight (OR: 1.05, 95% CI: 0.68-1.62). Importantly, among the cases that were overweight, those with mutated rs9939609 had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84-2.32) although these results were not statistical significant upon adjustment. Limitations of the study were the relatively small cohort and lack of access to the weight history of all our subjects. CONCLUSION: Results offer a research line to be followed with an expanded number of subjects that may provide a better statistical significance, to unravel the high mortality rate in this population.

Upregulation of EphA3 receptor after spinal cord injury.

Spinal cord injury (SCI) releases a cascade of events that leads to the onset of an inhibitory milieu for axonal regeneration. Some of these changes result from the presence of repulsive factors that may restrict axonal outgrowth after trauma. The Eph receptor tyrosine kinase (RTK) family has emerged as a key repellent cue known to be involved in neurite outgrowth, synapse formation, and axonal pathfinding during development. Given the nonpermissive environment for axonal regeneration after SCI, we questioned whether re-expression of one of these molecules occurs during regenerative failure. We examined the expression profile of EphA3 at the mRNA and protein levels after SCI, using the NYU contusion model. There is a differential distribution of this molecule in the adult spinal cord and EphA3 showed an increase in expression after several injury models like optic nerve and brain injury. Standardized semi-quantitative RT-PCR analysis demonstrated a time-dependent change in EphA3 mRNA levels, without alterations in beta-actin levels. The basal level of EphA3 mRNA in the adult spinal cord is low and its expression was induced 2 days after trauma (the earliest time point analyzed) and this upregulation persisted for 28 days post-injury (the latest time point examined). These results were corroborated at the protein level by immunohistochemical analysis and the cell phenotype identified by double labeling studies. In control animals, EphA3 immunoreactivity was observed in motor neurons of the ventral horn but not in lesioned animals. In addition, GFAP-positive cells were visualized in the ventral region of injured white matter. These results suggest that upregulation of EphA3 in reactive astrocytes may contribute to the repulsive environment for neurite outgrowth and may be involved in the pathophysiology generated after SCI.

Upregulation of EphA receptor expression in the injured adult rat spinal cord.

After spinal cord injury (SCI), the inability of supraspinal neurons to regenerate or reform functional connections is likely due to proteins in the surrounding microenvironment restricting regeneration. EphAs are a family of receptor tyrosine kinases that are involved in axonal guidance during development. These receptors and their ligands, the Ephrins, act via repulsive mechanisms to guide growing axons towards their appropriate targets and allow for the correct developmental connections to be made. In the present study, we investigated whether EphA receptor expression changed after a thoracic contusion SCI. Our results indicate that several EphA molecules are upregulated after SCI. Using semiquantitative RT-PCR to investigate mRNA expression after SCI, we found that EphA3, A4, and A7 mRNAs were upregulated. EphA3, A4, A6, and A8 receptor immunoreactivity increased in the ventrolateral white matter (VWM) at the injury epicenter. EphA7 had the highest level of immunoreactivity in both control and injured rat spinal cord. EphA receptor expression in the white matter originated from glial cells as coexpression in both astrocytes and oligodendrocytes was observed. In contrast, gray matter expression was localized to neurons of the ventral gray matter (motor neurons) and dorsal horn. After SCI, specific EphA receptor subtypes are upregulated and these increases may create an environment that is unfavorable for neurite outgrowth and functional regeneration.