Abstract 2851: Genetic polymorphisms and expression of SLC5A8 in prostate cancer
Authors: Hui-Yi Lin, Hyun Y. Park, Selina Radlein, Nupam Mahajan, Thomas A. Sellers, Maria Rincon, Babu Zachariah, Julio Pow-Sang, Sanghak Lee, Seungjoon Kim, Domenico Coppola, Vadivel Ganapathy, Jong Y. Park
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most common cancer in men, comprising approximately one-third of all male-specific cancers. SLC5A8 is a sodium-coupled transporter for short-chain fatty acids which are known to induce apoptosis by histone deacetylase inhibition. Previous studies suggest that SLC5A8 may function as a tumor suppressor gene whose silencing by epigenetic changes may contribute to carcinogenesis. For this reason, we investigated the role of expression and single nucleotide polymorphisms (SNPs) of SLC5A8 in prostate cancer risk and aggressiveness. We examined the association between common polymorphisms and risk for prostate cancer using a case-control study with 587 patients with incident primary prostate cancer, recruited at the Moffitt Cancer Center, and the James Haley VA Hospital and 347 age-matched controls, who were visiting the Lifetime Cancer Screening Center, which is affiliated with the Moffitt Cancer Center. All control subjects were male and had no previous diagnosis of cancer. We genotyped each study subject's DNA for four SNPs (rs164365, rs1709189, rs1399236, and rs1681096) in SLC5A8, by the TaqMan analysis. The frequencies of these SNPs were compared between cases and controls using logistic regression. Genotype distributions of all candidate SNPs in the controls followed Hardy-Weinberg equilibrium. In addition, SLC5A8 protein expression was estimated using innmunostained tissue microarray constructed from prostate tumor and normal tissues from BPH patients. We derived a semi-quantitative assessment by multiplying immunostain intensity and percentage of cells stained (range=0-9). We collected 140 prostate tumor tissues and 43 pairs of tumor and adjacent normal tissues from prostate cancer patients. From controls and BPH patients, 56 normal tissues were obtained. Among 43 pairs of tumor and normal tissues, SLC5A8 expression was significantly higher in tumor tissues than in their adjacent normal tissues (p&amp;lt;0.001). The similar result was shown in comparing tumor and normal tissues from independent individuals. SLC5A8 expression in 140 tumor tissues (median=4.5, IQR=3-6) was significantly higher than in 56 normal tissues (median=1.4, IQR=0-3, Wilcoxon test p&amp;lt;0.001). We observed a significant risk increase in individuals with at least one codon 490 SNP allele (rs164365) (OR=1.35, 95%=1.00-1.80) after adjusting for age and family history, especially among tall individuals (≥70 inches) (OR=1.83, 95%=1.22-2.73). Classification of patients by clinical aggressiveness did not show a significant difference of SLC5A8 genotype distribution and immunostating. Total 20 SNPs including 3 SNPs above in SLC5A8 were evaluated in the GWA study previously (CGEMS). Although these CGEMS data does not confirm the association between codon 490 polymorphism (rs164365) and prostate cancer risk, we observed significant SNP interactions associated with prostate cancer risk among individuals without a family history. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2851.