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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.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.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).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.

IMPACT: The Hispanic Alliance for Clinical and Translational Research Professional Development Core (PDC) will contribute to the improvement of the health of an increasing US Hispanic population, by supporting and training a new cadre of Hispanic/Latino CTR researchers and community leaders that understand this population’s prevalent health needs. OBJECTIVES/GOALS: To use the Professional Development Core (PDC) of the Hispanic Alliance for Clinical and Translational Research (Alliance) as a hub that coordinates training, mentoring programs, and grant support to address the need for more underrepresented minorities (URM) in clinical and translational research and mentoring. METHODS/STUDY POPULATION: PDC will: (1). Coordinate and offer an effective educational program based for new and mid-career researchers to address the gaps in research competencies on Hispanic/Latino health and healthcare through web-based asynchronous distance training, enhanced with face-to-face interactions. (2). Establish a robust mentoring program to address the mentoring gap for URM faculty by developing mentorship skills of faculty and researchers through a variety of resources, and offering protected time to mentor-mentee teams. (3). Design and implement a tailor-made curriculum to train scientists and community partners jointly, enabling them to carry out multidisciplinary research responsive to the Hispanic/Latino community health’s needs. RESULTS/ANTICIPATED RESULTS: From 2010 to 2019 the PDC supported over 1,000 researchers and faculty and provided 52 activities over the 9 years. PDC-supported researchers submitted 56 proposals and 21 grants (37.5.%) were awarded, for a total of $2, 225,751.00, and to published 94 peer-review papers. We expect that through Alliance PDC will sponsor at least 20 new trainees/mentees in Clinical and Translational Research (CTR), 20 new certified mentors, a continuous support program, and an increase of 30% in the scientific productivity (e.g., grants submission and peer-reviewed publications) of the Hispanic CTRs in Puerto Rico and the establishment of long-term links with the Hispanic community in Puerto Rico and across the United States to address its health needs. DISCUSSION/SIGNIFICANCE OF FINDINGS: The PDC programs are significant in addressing the need for qualified researchers and mentors that understand, have the know-how, and are interested in addressing the health needs of a growing USA Hispanic medically underserved population.

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..

Prostate cancer (PCa) mortality in Puerto Rico (PR) is significantly higher (28.3/100,000 men) compared to US mainland Hispanics. Obesity is prevalent in PR and has been associated with PCa mortality and aggressiveness. Polymorphisms rs9939609 and rs9930506 in the FTO gene have been associated with both obesity and PCa in other populations. Previous work in our laboratory has shown that Puerto Rican patients who underwent radical prostatectomy (RP) and also had at least one G allele in the FTO rs9930506 polymorphism exhibited a greater likelihood for low severity PCa. The aim of this work was to ascertain whether the presence of both polymorphisms (rs9930506 and rs9939609) in tandem correlated with PCa severity in this Puerto Rican population. The study population consisted of the pathology specimens of 294 Puerto Rican PCa patients, aged 40-79 years old who underwent RP as definitive treatment for PCa. Genomic DNA was extracted from normal seminal vesicle paraffin-embedded tissue. Polymorphisms were determined by RT-PCR. PCa severity was defined based on RP stage and Gleason Score. Chi-square test and logistic regression models were used to assess the correlation between FTO gene polymorphisms and PCa severity. Other factors such as BMI and age were considered in the model. We found that the A/G SNP in rs9930506 was present in 135 patients (45.9%). Likewise for rs9939609 we found the A/T SNP in 138 patients (46.9%). We found no statistically significant relationship between either polymorphism by itself and PCa severity. In 104 (35.4%) patients both SNPs were heterozygous. Of these, 77 (74%) were overweight or obese. Within this latter group, 55 (71.4%) exhibited low severity PCa. Data showed that those patients with simultaneous heterozygous forms had about 12% lower odds of low severity of PCa (95% CI: 0.52, 1.50), although no statistical significance was found for this relationship (p = 0.640). These results suggest that the presence of both polymorphisms in their heterozygous form may be related to low severity PCa in the obese/overweight group. Further studies are needed to understand the mechanisms that may be involved in this modulation of the development of severity in PCa in this population. This project was supported by RCMI grant G12MD007600 (Center for Collaborative Research in Health Disparities) and grant 8U54MD007587-03 (Puerto Rico Clinical and Translational Research Consortium) from the National Institute on Minority Health and Health Disparities, and by Award Grant Number# CA096297/CA096300 from the National Cancer Institute of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Citation Format: Jeannette Salgado-Montilla, Jorge Rodríguez-Caban, Lorena Gonzalez-Sepulveda, Ricardo Sanchez-Ortiz, Margarita Irizarry-Ramirez. Presence of FTO rs9939609 and rs9930506 and severity of prostate cancer in Puerto Ricans. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4836. doi:10.1158/1538-7445.AM2015-4836

e16033 Background: The mortality from prostate cancer (PCA) is high in Hispanic Puerto Rican males (HPRM) living on the island of Puerto Rico (PR) and in African American (AA) menliving in the cont...

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.