title: Genetic variations in micro-RNA biogenesis genes and clinical outcomes in non-muscle-invasive bladder cancer.
abstract: Micro-RNAs (miRNAs) are small non-coding RNA molecules, which can act as either oncogenes or tumor suppressors. Dysregulated expression of miRNA genes have been implicated in the development of many different cancers. We hypothesize that genetic variations in miRNA biogenesis genes may be associated with the prognosis of bladder cancer. We genotyped 76 single nucleotide polymorphisms (SNPs) in eight miRNA biogenesis genes in 421 patients with non-muscle-invasive bladder cancer (NMIBC). We analyzed the associations of SNPs with recurrence and progression in all patients as well as stratified by treatment: transurethral resection (TUR) alone or TUR plus intravesical bacillus Calmette-Guérin (BCG) instillation. Two SNPs were significantly associated with tumor recurrence in TUR only subgroup after adjustment for multiple comparisons (Q < 0.1). The most significant SNP was rs197412 in DDX20: the variant allele conferred a decreased risk of recurrence [hazard ratio (HR) = 0.58, 95% confidence interval (95% CI) = 0.40-0.82]. This SNP was validated in a separate group of 586 NMIBC patients and the pooled HR was 0.62 (95% CI = 0.48-0.81, P < 0.001). Two linked SNPs (rs2073778 and rs720012) in DGCR8 showed significant association with tumor progression (HR = 4.00, 95% CI = 1.53-10.46, P = 0.005). A strong gene-dosage effect was observed with higher risk for tumor recurrence and progression with increasing number of unfavorable genotypes. Haplotype and survival tree analyses further characterized the association of miRNA-related SNPs with tumor recurrence and progression. Taken together, our results indicate that genetic variants in miRNA biogenesis pathway may influence bladder cancer clinical outcome in NMIBC patients.
authors: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Hung-Lung
authors: HL
authors: Ke
authors: Meng
authors: M
authors: Chen
authors: Yuanqing
authors: Y
authors: Ye
authors: Michelle A T
authors: MA
authors: Hildebrandt
authors: Wen-Jeng
authors: WJ
authors: Wu
authors: Hua
authors: H
authors: Wei
authors: Maosheng
authors: M
authors: Huang
authors: David W
authors: DW
authors: Chang
authors: Colin P
authors: CP
authors: Dinney
authors: Xifeng
authors: X
authors: Wu
mesh_terms: D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D035683:MicroRNAs