Summary: | Increasing evidence shows that dysregulated expression of long non-coding (lnc)RNAs can serve as diagnostic or prognostic markers in urothelial cell carcinoma (UCC), the most common pathological type of bladder cancer. lncRNA <i>HOX transcript antisense RNA</i> (<i>HOTAIR</i>) was shown to promote tumor progression and be associated with a poor prognosis in multiple cancers including bladder cancer. Polymorphisms of <i>HOTAIR</i> were recently linked to a predisposition for diverse malignancies. Herein we conducted a case-control study to evaluate whether genetic polymorphisms of <i>HOTAIR</i> were associated with UCC risk and clinicopathologic characteristics. Four loci (rs920778 T>C, rs1899663 G>T, rs4759314 A>G, and rs12427129, C>T) of <i>HOTAIR</i> were genotyped by a TaqMan allelic discrimination method in 431 cases and 862 controls. We found that female patients who carried AG + GG genotype of rs4759314 were associated with an increased UCC risk after controlling for age and tobacco consumption (adjusted odds ratio (AOR) = 1.92, 95% confidence interval (CI): 1.01⁻3.64, <i>p</i> = 0.047) and a lower overall survival rate (<i>p</i> = 0.008). Moreover, patients with a smoking habit or younger age (≤65 years), who had at least one T allele of <i>HOTAIR</i> rs12427129 were at a higher risk of developing advance tumor T satge (<i>p</i> = 0.046), compared to those patients with CC homozygotes. In contrast, rs920778 C allele carriers were negatively correlated with the development of lymph node metastasis (OR = 0.51, 95% CI: 0.28⁻0.94, <i>p</i> = 0.031). Further analyses of clinical datasets revealed correlations of the expression of <i>HOTAIR</i> with tumor metastasis and a poor survival rate in patients with UCC. Our results verified the diverse impacts of <i>HOTAIR</i> variants on UCC susceptibility and clinicopathologic characteristics.
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