Lin Yadi, Ge Yuqiu, Wang Yunyan, Ma Gaoxiang, Wang Xiaowei, Liu Hanting, Wang Meilin, Zhang Zhengdong, Chu Haiyan
Department of Environmental Genomics, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Urology, Huai-An First People's Hospital, Nanjing Medical University, Huai-an, China.
Gene. 2017 Sep 5;627:226-232. doi: 10.1016/j.gene.2017.06.021. Epub 2017 Jun 13.
The long noncoding RNA PCAT1 is an important gene involved in urinary tumors. In this study, we aimed to explore the association between polymorphisms in PCAT1 and bladder cancer susceptibility.
A two-stage case-control study was conducted to assess the association between four tagging SNPs (i.e., rs4871771, rs1902432, rs16901904 and rs710886) and bladder cancer risk. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated with unconditional univariate and multivariate logistic regression.
At the first stage of discovery, we identified that SNP rs710886A>G was significantly associated with bladder cancer risk (OR=0.86, 95% CI=0.74-0.99, P=0.046). At the following stage of validation, individuals with GG genotype were found to have a significant reduction in bladder cancer risk compared with those carrying AA genotype (adjusted OR=0.83, 95% CI=0.74-0.93, P=0.001). Furthermore, stratified analyses showed that protective effect of rs710886 was more pronounced in subgroup of age>60 and never smoking, and had little to do with sex. Besides, rs710886 was identified as an eQTL for PCAT1. G allele was consistent with lower PCAT1 expression.
This study indicates that genetic variants in lncRNA PCAT1 were associated with bladder cancer susceptibility and the SNP rs710886 may act as a potential biomarker for bladder cancer risk.
长链非编码RNA PCAT1是参与泌尿系统肿瘤的一个重要基因。在本研究中，我们旨在探讨PCAT1基因多态性与膀胱癌易感性之间的关联。
开展一项两阶段病例对照研究，以评估4个标签单核苷酸多态性（即rs4871771、rs1902432、rs16901904和rs710886）与膀胱癌风险之间的关联。采用无条件单因素和多因素logistic回归计算比值比（OR）及其95%置信区间（CI）。
在发现阶段的第一阶段，我们发现单核苷酸多态性rs710886A>G与膀胱癌风险显著相关（OR=0.86，95%CI=0.74-0.99，P=0.046）。在随后的验证阶段，发现与携带AA基因型的个体相比，具有GG基因型的个体患膀胱癌的风险显著降低（校正OR=0.83，95%CI=0.74-0.93，P=0.001）。此外，分层分析显示，rs710886的保护作用在年龄>60岁且从不吸烟的亚组中更为明显，与性别无关。此外，rs710886被确定为PCAT1的一个表达数量性状基因座。G等位基因与较低的PCAT1表达一致。
本研究表明lncRNA PCAT1中的基因变异与膀胱癌易感性相关，单核苷酸多态性rs710886可能作为膀胱癌风险的潜在生物标志物。
