Association of rs8444 polymorphism in the LASS2 3′-UTR and bladder cancer risk in Chinese population
Association of rs8444 polymorphism in the LASS2 3′-UTR and bladder cancer risk in Chinese population
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LASS2 3-UTR rs8444 多态性与中国人群膀胱癌风险的关联
DOI：
10.1097/cej.0000000000000551
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发表时间：
2020-07-01
影响因子：
2.4
通讯作者：
Wang, Jiansong
中科院分区：
文献类型：
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作者：
Huang, Yinglong;Wang, Haifeng;Wang, Jiansong
本研究旨在探讨LASS 2基因3 '非翻译区单核苷酸多态性与中国人群膀胱癌发病风险的关系。我们首先对105名膀胱癌患者和100名对照受试者进行了LASS 2 -3 '-UTR的PCR和测序。采用多因素Logistic回归分析105例膀胱癌患者的单核苷酸多态性频率与膀胱癌易感性及临床特征的关系。此外，还对58例患者进行了生存曲线和考克斯回归分析，以探讨单核苷酸多态性对临床结局的影响。最后，通过定量逆转录PCR和免疫组织化学方法，探讨单核苷酸多态性对LASS 2表达的影响。我们发现位于LASS 2基因3 '-UTR的单核苷酸多态性（rs 8444 C>T）与膀胱癌的风险显著相关。rs 8444 T基因型在膀胱癌组中的频率较高，且与临床预后相关。rs 8444基因型分布与膀胱癌的淋巴结转移分期、组织学分级及远处转移无明显相关性。此外，我们证明rs 8444 C>T可以通过单核苷酸多态性相关的mRNA稳定性影响LASS 2的表达。本研究结果显示LASS 2 -3 '-UTR rs 8444 C>T多态性与膀胱癌的个体危险性和总生存率显著相关，提示rs 8444 TT基因型可能是中国人群膀胱癌易感性和临床预后的独立危险因素。
The aim of the present study was to explore the correlations between single nucleotide polymorphisms inLASS2gene 3 '-untranslated regions and bladder cancer risk in Chinese population. We first performed PCR and sequence for LASS2-3 '-UTR in 105 bladder cancer patients and 100 control subjects. Next, multivariate logistic regression analysis was used to determine the relationship between single nucleotide polymorphisms frequency and susceptibility of bladder cancer, and clinical features in 105 cases. In addition, survival curves and Cox Regression analysis were used to investigate the effect of single nucleotide polymorphisms on clinical outcome in 58 cases. Finally, quantitative reverse-transcription PCR and immunohistochemical were performed to explore the influence of single nucleotide polymorphisms on LASS2 expression. We found that a single nucleotide polymorphism (rs8444 C>T) located in the 3 '-UTR of LASS2 was significantly associated with the risk of bladder cancer. We also showed the frequency of rs8444 T genotype was higher in bladder cancer group and correlated with the risk of clinical prognosis. Yet, there were no significant correlations between T/C allele frequencies and the distributions of rs8444 genotype and tumor-node-metastasis stage, histological grade and distant metastasis in bladder cancer. Furthermore, we demonstrated that rs8444 C>T could affect LASS2 expression by single nucleotide polymorphism-related mRNA stability. Our results showed that LASS2-3 '-UTR rs8444 C>T polymorphism was significantly associated with the individual risk and the poor overall survival of bladder cancer, suggesting that rs8444 TT genotype maybe act as an independent risk factor of susceptibility and clinical prognosis for bladder cancer in Chinese population.