title: Genetic variants in miRNAs predict bladder cancer risk and recurrence.
abstract: miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71-0.90, P = 2.92 × 10(-4)]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.
authors: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.
authors: Meilin
authors: M
authors: Wang
authors: Haiyan
authors: H
authors: Chu
authors: Pu
authors: P
authors: Li
authors: Lin
authors: L
authors: Yuan
authors: Guangbo
authors: G
authors: Fu
authors: Lan
authors: L
authors: Ma
authors: Danni
authors: D
authors: Shi
authors: Dongyan
authors: D
authors: Zhong
authors: Na
authors: N
authors: Tong
authors: Chao
authors: C
authors: Qin
authors: Changjun
authors: C
authors: Yin
authors: Zhengdong
authors: Z
authors: Zhang
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D035683:MicroRNAs