Abstract B67: FTO and APO SNPs Impact Prostate Cancer Severity and Risk in Puerto Rican Men

Abstract

Abstract In Puerto Rico, the age-adjusted incidence rate of prostate cancer (PCa) between 2008 and 2012 was 152.8 per 100,000 men, while the age-adjusted death rate for the same period was 28.4 per 100,000 men, which is higher than for Hispanics (21.2) and white non Hispanics (26.4) in the United States. In addition according to statistics of the Behavioral Risk Factor Surveillance System (BRFSS) for 2012, 37.8% of citizens were overweight and 28.4 % were obese. Obesity has been associated with a higher aggressiveness and mortality of PCa. In a previous work, our group established a relationship between high triglycerides levels in serum and PCa. In other populations, FTO polymorphisms rs9930506 (FTO506) and rs9939609 (FTO609) have been associated with both, obesity and PCa risk. In addition, ApoA5 polymorphism rs3135506 (APO506) has been associated with high triglycerides serum levels. We hypothesized that these genes involved in lipids' metabolism and fat deposition may influence PCa phenotype in Puerto Rican men. Our aim was to establish a possible relationship between PCa risk/severity and obesity/lipids-related gene polymorphisms (FTO506, FTO609 and APO506) in a cohort of Puerto Rican men with PCa. Methods: Genomic DNA was extracted from FFPE non-tumor seminal vesicles from pathology specimens from Puerto Rican men aged 40-79 years old (n=512) who underwent radical prostatectomy (RP) as the first treatment for PCa, and from whole blood collected in EDTA tubes, from healthy age-matched Puerto Rican men (controls). Genotyping was done in a Step One, Applied Biosystems. Severity was defined using RP's Gleason score and tumor stage. Chi-square test and logistic regression models were used to assess the association between PCa severity and the genotype of FTO506, FTO609, APO506, and BMI, PSA and age. Results: For FTO506 and FTO609 the heterozygous forms (A/G and T/A, respectively) were the most prevalent, while the wild type (G/G) was the predominant form of APO506. After adjusting for all variables in the model simultaneously, PCa risk was significantly related to FTO609 (p=0.006). PCa severity was significantly associated to APO506 (p=0.029), age (p=0.005) and PSA (p=0.002). In addition, FTO506 was marginally associated with PCa risk (p=0.082). Conclusion: Our results suggest that the presence of FTO506 and FTO609 are related to risk of having PCa in this cohort of Puerto Rican men, and that APO506 influences severity of PCa. Further analyses to establish the mechanisms by which APO506 modulates severity of PCa are underway. Results prompt the need for the evaluation of lipid panels and of lipid related polymorphisms as part of PCa patients' management. This project was supported by the Puerto Rico Clinical and Translational Research Consortium (Award Number 2U54MD007587) from the NIHMD and by the UPR/MDACC: Partnership for Excellence in Cancer Research Program at the UPR MSC (Award Grant Number# CA096297/CA096300) Citation Format: Margarita Irizarry Ramírez, Jorge Rodríguez Cabán, Jeannette Salgado Montilla, Beatriz Zayas, Nicole Serrant. FTO and APO SNPs Impact Prostate Cancer Severity and Risk in Puerto Rican Men. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B67.