Abstract

Abstract 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

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