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Abstract
Abstract MicroRNAs (miRNAs) are a group of short non-protein-coding RNAs regulating gene expression in eukaryotes, which can act as oncogenes or tumor suppressors. To test the hypothesis that genetic variations in the miRNA biogenesis genes are associated with the prognosis of bladder cancer, we genotyped 76 single nucleotide polymorphisms (SNPs) in 8 genes (DDX20, DGCR8, DICER1, EIF2C1, GEMIN4, RAN, RNASEN and XPO5) from the miRNA biogenesis pathway in 421 patients with non-muscle invasive bladder cancer. Eight SNPs reached significant association with cancer recurrence in patients who received trans-urethral resection (TUR) only, and three SNPs in patients who received intravesical Bacillus Calmette-Guérin (BCG) instillation. The most significant SNP in TUR group was rs197412 in DDX20, with the variant allele conferring a 42% decreased risk of recurrence (HR=0.58, 95% CI=0.40-0.82, P=0.002). The most significant SNP in BCG group was rs563002 in DDX20, with the variant allele conferring an increased risk of recurrence (HR=2.80, 95% CI=1.30-6.04, P=0.009). In addition, seven SNPs showed significant association with cancer progression. The most significant SNP associated with progression was rs3087833 in GEMIN4, with the variant allele conferring an increased risk of progression (HR=9.73, 95% CI=2.31-40.92, P=0.002). Finally, we performed cumulative effect analysis for the number of unfavorable genotype on bladder cancer recurrence and prognosis. These data demonstrated that miRNA-related SNPs may impact the recurrence and progression in bladder cancer patients. Further study in independent large population and functional characterization are needed to validate these results. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1150. doi:10.1158/1538-7445.AM2011-1150
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