| ObjectiveThe long noncoding RNA(LncRNA)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.BackgroundBladder cancer is the most common urological tumor in China and western countries.Although the incidence in our country is slightly lower than that of the more common digestive and respiratory malignancies,the incidence of bladder cancer is on the rise in China.This may be related to the acceleration of the diet structure and social aging trend,and the in-depth study on the pathogenesis of bladder cancer is becoming more and more important.According to previous studies,we can see that the cell abnormalities caused by genetic variation are highly correlated with the occurrence of bladder cancer,but as the researchers’ research on the tumor progressively deepened,researchers have gradually found that epigenetic regulation mechanism plays an important role in the regulation of malignant tumor progression.A critical adjustment effect.With the progress of the human genome project,a large number of studies have found that genetic variation in key genes has an important influence on the structure,expression and function of the gene,which leads to changes in the biological regulation function of the body.As the human genome project,a large number of studies have found that genes of key position of genetic variation of genetic structure,expression and molecular regulation function have a major impact,leading to the change of the body part of the biological control function.LncRNA PCAT1 plays an important role in the development of urinary tract tumor.Studies have found that many single nucleotide polymorphisms can affect thebiological processes of various tumors in LncRNA.This study aims to study the relationship between PCAT1 polymorphism and bladder cancer susceptibility.The long noncoding RNA PCAT1 is an important gene involved in urinary system.Publicated studies have found many single nucleotide polymorphisms in LncRNAs could affect biological process of multifarious carcinomas.In this study,we explored the association between polymorphisms in PCAT1 and bladder cancer susceptibility.MethodsA 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.This study included 1606 patients with bladder cancer and 2386 cases of normal controls(GWAS studies in 578 patients and 1006 controls),the second phase TaqMan genotyping including men in the study of 1028 cases of patients with bladder cancer,and also we selected 1381 healthy controls.The correlation between the four TagSNPs of candidate Lnc RNA PCAT1 and the risk of bladder cancer was analyzed.This experiment in two stages of case-control study(GWAS stage,followed by Taqman genotyping stage)analysis of the candidate LncRNA PCAT1 of 4 TagSNPs is closely related to the occurrence of bladder cancer,we through the multifactor conditional logistic regression analysis to calculate the odds ratio(ORs)and 95% confidence limits(CIs),evaluate the correlation between SNPs variation and bladder cancer risk.ResultsAt the first stage of discovery,we identified that SNP rs710886 A>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 thosecarrying AA genotype(adjusted OR = 0.83,95%CI=0.74-0.93,P=0.001).The allele of G showed a significant protective effect on bladder cancer(after adjustment OR:0.80,95% CI: 0.67-0.96).In addition,stratified analysis showed that the risk of bladder cancer in the elderly was significantly lower(over 60 years old).Adjustment OR: 0.77,95% CI: 0.67-0.88).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.ConclusionThis study reveals the important role of Lnc RNA PCAT1 rs710886 polymorphism in bladder cancer risk.PCAT1 rs710886 is expected to be used as a biomarker for predicting the risk of bladder cancer.This study is expected to further reveal the LncRNAs in its role in the development of bladder cancer and their possible biological mechanisms to provide theoretical basis for help to bladder cancer etiology research and bladder cancer prevention and early screening. |
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