Abstract 2558: miRNA-related gene variants and prostate cancer aggressiveness and recurrence.
Authors: Amankwah Ernest K. , Lin Hui-Yi , Park Hyun , Radlein Selina , Pow-Sang Julio , Hakam Ardeshir , Tsai Ya-Yu , Park Jong Y. 
Published: August 2014

Introduction: miRNA expression has been correlated with prostate cancer aggressive and recurrence. However, the role of miRNA-related gene variants in prostate cancer aggressiveness and recurrence has not been adequately studied. In this study, we evaluated the association between single nucleotide polymorphisms (SNPs) in miRNA-related genes and prostate cancer aggressiveness and recurrence.

Methods: We conducted a two-stage (discovery and replication) analysis of 136 miRNA-related gene variants (in 18 genes) in aggressive and non-aggressive prostate cancer cases. A discovery dataset of 437 aggressive and 603 non-aggressive cases was derived from a historical cohort of prostate cancer cases treated at the Moffitt Cancer Center from 1987 to 2003. A replication set of 659 aggressive and 492 non-aggressive cases was derived from existing genome-wide association data from Cancer Genetic Markers of Susceptibility (CGEMS). In both datasets, patients with a Gleason score &gt; 7 or stage &gt; III were considered to have aggressive disease and all other patients were categorized as non-aggressive. Associations between SNPs and aggressive disease were evaluated using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95%CI). We also evaluated the associations between SNPs and recurrence-free survival using Cox regression models to estimate hazard ratios (HR) and 95%CI among 245 recurrent and 979 non-recurrent cases. We calculated q-values to estimate false discovery rates in the analysis of recurrence.

Results: For the analysis of aggressiveness, ten SNPs in seven genes (EIF2C2 [rs7009635, rs2280833 and rs13276958], FMR1 [rs28282], GEMIN4 [rs2291779], LIN28B [rs1149280], PIWIL1 [rs1106042], RAN [rs14035] and XPO5 [rs7752811, rs7748977] were significantly associated with aggressive prostate cancer in the discovery dataset. Five of the 10 significant SNPs had data available in the replication dataset, but none of them was statistical significant in this dataset. For the analysis of recurrence, a total of 13 SNPs in seven genes were associated with recurrence-free survival (P-values &lt; 0.05 and q-values ≤0.12): one each in DDX20 (rs12745851), PRKRA (rs4894020) and Lin28 (rs17163904); two each in EIF2C2 (rs13273553 and rs2977491) and LIN28B (rs170276 and rs7750532); and three each in GEMIN4 (rs7813, rs2291779 and rs910925) and RNASEN (rs673019, rs3805521 and rs1749275). The most significant association was observed at DDX20 rs12745851 (HR=1.52, 95%CI=1.20-1.91, p=0.0004, q=0.04).

Conclusion: Findings from this study suggest that variants in miRNA-related genes may influence prostate cancer recurrence, but not aggressiveness. Further studies are warranted to confirm these findings.

Citation Format: Ernest K. Amankwah, Hui-Yi Lin, Hyun Park, Selina Radlein, Julio Pow-Sang, Ardeshir Hakam, Ya-Yu Tsai, Jong Y. Park. miRNA-related gene variants and prostate cancer aggressiveness and recurrence. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2558. doi:10.1158/1538-7445.AM2013-2558