Is switching intravesical chemotherapeutic agents beneficial in short-term recurrent high-risk non-muscle-invasive bladder tumors? A 5-year retrospective study.

OBJECTIVE: To explore if switching intravesical chemotherapeutic agents is beneficial in short-term recurrences of high-risk non-muscle-invasive bladder cancer (NMIBC) following the failure of preceding intravesical therapy. MATERIALS AND METHODS: From June 2010 to October 2015, 205 patients with NMIBC who experienced tumor recurrence within a year after receiving first-line intravesical chemotherapy (IVC) were classified into two groups. After a second complete transurethral resection (TUR) process, we immediately altered the intravesical instillation agent for 107 patients (group A). In contrast, the remaining 98 patients (group B) continued using their original intravesical instillation agent. After transurethral resection of the bladder tumor (TURBT), all patients received either an immediate instillation of epirubicin (EPI), gemcitabine (GEM), or hydroxycamptothecin (HCPT), followed by regular induction and maintenance instillations. Recurrence and progression rates were evaluated using the Chi-square test, and recurrence-free survival (RFS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: In this study, there was no significant difference in either the 5-year tumor recurrence or progression rates between the two groups (p > 0.05) The Kaplan-Meier plot showed no difference in progression-free or recurrence-free survival between the two groups. CONCLUSION: Switching IVC agents does not improve RFS and PFS for patients with short-term recurrent high-risk NMIBC.

Programming conformational cooperativity to regulate allosteric protein-oligonucleotide signal transduction.

Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we develop a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generate a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implement allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields.

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer.

Increasing evidences have demonstrated that circular RNA (circRNAs) plays a an essential regulatory role in initiation, progression and immunotherapy resistance of various cancers. However, circRNAs have rarely been studied in bladder cancer (BCa). The purpose of this research is to explore new circRNAs and their potential mechanisms in BCa. A novel ceRNA-regulated network, including 87 differentially expressed circRNAs (DE-circRNAs), 126 DE-miRNAs, and 217 DE-mRNAs was constructed to better understanding the biological processes using Cytoscape 3.7.1 based on our previously high-throughput circRNA sequencing and five GEO datasets. Subsequently, five randomly selected circRNAs (upregulated circ_0001681; downregulated circ_0000643, circ_0001798, circ_0006117 and circ_0067900) in 20 pairs of BCa and paracancerous tissues were confirmed using qRT-PCR. Functional analysis results determined that 772 GO functions and 32 KEGG pathways were enriched in the ceRNA network. Ten genes (PFKFB4, EDNRA, GSN, GAS1, PAPPA, DTL, TGFBI, PRSS8, RGS1 and TCF4) were selected for signature construction among the ceRNA network. The Human Protein Atlas (HPA) expression of these genes were consistent with the above sequencing data. Notably, the model was validated in multiple external datasets (GSE13507, GSE31684, GSE48075, IMvigor210 and GSE32894). The immune-infiltration was evaluated by 7 published algorithms (i.e., TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL and EPIC). Next, Correlations between riskscore or risk groups and clinicopathological data, overall survival, recognized immunoregulatory cells or common chemotherapeutic agents of BCa patients were performed using wilcox rank test, chi-square test, cox regression and spearman's correlation analysis; and, these results are significant. According to R package "GSVA" and "clusterProfiler", the most significantly enriched HALLMARK and KEGG pathway was separately the 'Epithelial Mesenchymal Transition' and 'Ecm Receptor Interaction' in the high- vs. low-risk group. Additionally, the functional experiments in vitro also revealed that the overexpression of has_circ_0067900 significantly impaired the proliferation, migration, and invasion capacities of BCa cells. Collectively, the results of the current study provide a novel landscape of circRNA-associated ceRNA-regulated network in BCa. The ceRNA-associated gene model which was constructed presented a high predictive performance for the prognosis, immunotherapeutic responsiveness, and chemotherapeutic sensitivity of BCa. And, has_circ_0067900 was originally proposed as tumor suppressor for patients with BCa.

Low-dose hexavalent chromium(VI) exposure promotes prostate cancer cell proliferation by activating MAGEB2-AR signal pathway.

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with several malignancies, such as lung cancer, but little information was available about the effects of its low-dose environmental exposure in prostate cancer. Our previous study has shown that low-dose Cr(VI) exposure could promote prostate cancer(PCa) cell growth in vitro and in vivo. In the present study, we furthermore found that low-dose Cr(VI) exposure could induce DNA demethylation in PCa cells. Based on our transcriptome sequencing data and DNA methylation database, we further identified MAGEB2 as a potential effector target that contributed to tumor-promoting effect of low-dose Cr(VI) exposure in PCa. In addition, we demonstrated that MAGEB2 was upregulated in PCa and its knockdown restrained PCa cell proliferation and tumor growth in vitro and in vivo. Moreover, Co-IP and point mutation experiments confirmed that MAGEB2 could bind to the NH2-terminal NTD domain of AR through the F-box in the MAGE homology domain, and then activated AR through up-regulating its downstream targets PSA and NX3.1. Together, low-dose Cr(VI) exposure can induce DNA demethylation in prostate cancer cells, and promote cell proliferation via activating MAGEB2-AR signaling pathway. Thus, inhibition of MAGEB2-AR signaling is a novel and promising strategy to reverse low-dose Cr(VI) exposure-induced prostate tumor progression, also as effective adjuvant therapy for AR signaling-dependent PCa.

Reducing Postoperative Recurrence of Early-Stage Hepatocellular Carcinoma by a Wound-Targeted Nanodrug.

New strategies to decrease risk of relapse after surgery are needed for improving 5-year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound-targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti-PD-L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface-coated with platelet membrane (PM) to achieve surgical site targeting in a self-amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti-PD-L1 antibody on the PM surface. The resulting nano-formulation, abbreviated as a-PM-S-MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a-PM-S-MSNP generate potent anti-HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti-HCC immunity and anti-angiogenesis effect at tumor sites. More importantly, microscopic inspection of a-PM-S-MSNP treated mice shows that 2 out 6 are histologically tumor-free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a-PM-S-MSNP can efficiently inhibit post-surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Long noncoding RNAs, ENST00000598996 and ENST00000524265, are correlated with favorable prognosis and act as potential tumor suppressors in bladder cancer.

Bladder cancer (BC) is a serious malignancy worldwide due to its distant metastasis and high recurrence rates. Increasing evidence has indicated that dysregulated long non­coding RNAs (lncRNAs) are involved in tumorigenesis and progression in multiple malignancies. However, their clinical significances, biological functions and molecular mechanisms in BC remain poorly understood. Hence, the present study investigated the expression profile of lncRNAs and mRNAs in five BC tissues and the corresponding adjacent normal specimens using high­throughput RNA sequencing (RNA­seq). A total of 103 differentially expressed (DE) lncRNAs were identified, including 35 upregulated and 68 downregulated ones in BC tissues. Similarly, a total of 2,756 DE­mRNAs were detected, including 1,467 upregulated and 1,289 downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, and lncRNA­miRNA­mRNA network analyses suggested that these dysregulated lncRNAs are potentially implicated in the onset and progression of BC. Subsequently, four lncRNAs (upregulated ENST00000433108; downregulated ENST00000598996, ENST00000524265 and ENST00000398461) and two mRNAs (upregulated CCNB1 and CDK1) in 64 pairs of BC and adjacent normal tissues and four BC cell lines were detected using reverse transcription­quantitative PCR and these results were consistent with the sequencing data. Additionally, Fisher's exact test, Kaplan­Meier plots, and Cox regression analyses were used for elucidating the clinical values of ENST00000598996 and ENST00000524265. Furthermore, a receiver operating characteristic curve was constructed to assess their diagnostic values. The low expression level of ENST00000598996 and ENST00000524265 was correlated with unfavorable clinicopathological parameters, and shorter progression­free and overall survival time, whereas, ENST00000433108 was not associated with either. The in vitro functional experiments also revealed that the overexpression of ENST00000598996 and ENST00000524265 decreased the proliferation, migration, and invasion abilities of BC cells. Collectively, the results of the present study provide a novel landscape of lncRNA and mRNA expression profiles in BC. In addition, the results also indicated that ENST00000598996 and ENST00000524265 may serve as tumor suppressors, potential diagnostic biomarkers and prognostic predictors for patients with BC.

Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high-throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA-microRNA-mRNA, and protein-protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real-time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase-R+ resistance experiments. In addition, Fisher's exact test, Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P < .0001) and 0.790 (P < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer.

TACC3 promotes prostate cancer cell proliferation and restrains primary cilium formation.

Although primary cilia abnormalities have been frequently observed in multiple cancers, including prostate cancer (PCa), the molecular mechanisms underlying primary ciliogenesis repression in PCa cells remain unclear. Transforming acidic coiled-coil protein-3 (TACC3), whose deregulation has been implicated in the pathogenesis of several types of cancer, is a key centrosomal protein that plays a crucial role in centrosome/microtubule dynamics, potentially impacting primary cilium generation. Here, we showed that TACC3 was markedly upregulated in PCa and that knockdown of TACC3 restrained tumorigenesis and tumor growth in vitro and in vivo. Additionally, we found that TACC3 interacts with filamin A, and elevated levels of TACC3 disrupted the interaction between filamin A and meckelin, thereby restraining primary cilium formation in PCa cells.

Kinase PIM1 promotes prostate cancer cell growth via c-Myc-RPS7-driven ribosomal stress.

Ribosomal stress is known to increase cancer risk; however, the molecular mechanism underlying its various effects on cancer remains unclear. To decipher this puzzle, we investigated the upstream signaling pathway that might be involved in promoting ribosomal stress that leads to tumor progression. Our results suggested that inhibition of kinase PIM1 attenuated PC3 cell growth and motility following the condensed cellular body and decreased protein translation in PIM1-inhibited cells. In addition, PIM1 was found to be a component of the small 40S ribosomal subunit and could regulate the expression of ribosomal small subunit protein 7 (RPS7). Our investigation also revealed that PIM1 enhanced the protein stability of c-Myc. Furthermore, a functional E-box motif was found upstream of the transcription start site in RPS7, and RPS7 has been proven to be a transcriptional target of c-Myc. Additionally, knocking down RPS7 dramatically reduced cell growth in vitro and in vivo, whereas enhancing RPS7 expression reversed the condensed cellular body and decreased protein translation resulted from PIM1 inhibition. Finally, biochemical recurrence-free survival and overall survival analysis indicated that the concomitant upregulation of PIM1 and RPS7 correlated with the worst prognosis of prostate cancer (PCa). Overall, our results demonstrated that kinase PIM1 promotes cell growth through c-Myc-RPS7-induced ribosomal stress in PCa. These findings substantially expanded our understanding on the molecular mechanism of PIM1-promoted abnormal ribosomal biosynthesis in tumorigenesis and tumor progression in PCa. Therapies that target molecules involved in PIM1-RPS7-induced ribosomal stress could provide a promising approach to treating PCa.

Selective Actionable and Druggable Protein Kinases Drive the Progression of Neuroendocrine Prostate Cancer.

Current clinical anti-androgen therapies in advanced prostate cancer (PCa) are driving an increased incidence of neuroendocrine prostate cancer (NEPC), a histological variant exhibiting reduced androgen receptor levels and expression of neuroendocrine markers. The mechanisms underlying the development of NEPC are poorly understood. A set of available data from a well-validated xenograft model of NEPC was used to analyze the exact role of protein kinase (PK) played in the development of NEPC. Fifty-four actionable and druggable PKs, mainly enriched in PI3K-Akt, mTOR, and MAPK signaling pathways, were screened out from the drastically changed PKs during NEPC transdifferentiation. Further analysis based on the crosstalk of these above signaling pathways finally singled out 10 PKs considered drivers and therapeutic targets in the development and treatment of NEPC. In vitro, the variation trend of PK expression observed during NEPC transdifferentiation could be recapitulated in PCa cell lines with different malignant degree. The predicted kinase targets exhibited different sensibilities in the restriction of PC3 cell growth. Selective actionable and druggable PKs may act as drivers in the progression of NEPC, and most of them can be used as potential therapeutic targets in clinical practice.

Polymorphism in IGFBP3 gene is associated with prostate cancer risk: an updated meta-analysis.

OBJECTIVE: Insulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism. METHODS: A comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case-control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model. RESULTS: Eighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA - OR =1.16, 95% CI: 1.08-1.25) and in recessive model (CC vs AA+AC - OR =1.11, 95% CI: 1.04-1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA - OR =1.11, 95% CI: 1.05-1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05-1.14). Further stratification analysis revealed that the association between -202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02-1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model. CONCLUSION: Our meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa.

The value of extensive transurethral resection in the diagnosis and treatment of nonmuscle invasive bladder cancer with respect to recurrence at the first follow-up cystoscopy.

OBJECTIVE: To evaluate the value of extensive transurethral resection (TUR) in the diagnosis and treatment of nonmuscle invasive bladder cancer (NMIBC) and its further impact on the recurrence rate at the first follow-up cystoscopy (RR-FFC). PATIENTS AND METHODS: A retrospective review of consecutive series of 523 patients with NMIBCs who underwent TUR from June 2009 to July 2015 at the Second Hospital of Tianjin Medical University was conducted. Extensive TURs were performed by taking additional tumor base and marginal specimens for 317 patients (group 1). Extensive TURs were not done in the other 206 patients (group 2). Urine cytology and follow-up cystoscopy were performed at 3 months after the initial TUR. The positive findings of additional specimens were noted and it was found whether or not the diagnosis and treatment plan had changed in group 1. Also, a comparison was made of the RR-FFC between group 1 and 2. RESULTS: There were 51/317 (16.1%) patients whose additional specimens revealed pathological findings such as Ta, T1, and carcinoma in situ diseases. Of these positive findings, 6/51 (11.8%) were Ta stage, 16/51 (31.4%) were T1 stage, 18/51 (35.3%) were T2 stage, and 11/51 (21.5%) were carcinoma in situ. Due to the positive findings, 29/317 (9.1%) patients had their final diagnosis changed and 45/317 (14.2%) had their post-TUR treatment plans adjusted. The RR-FFC of group 1 and 2 were 4.7% (14/297) and 13.1% (27/206), respectively (P=0.001). CONCLUSION: Routine extensive TUR is helpful for the pathological diagnosis and the post-TUR treatment of NMIBC. Furthermore, it can significantly reduce the RR-FFC of NMIBC, especially in patients with T1 stage or high-grade disease.

Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study.

OBJECTIVE: The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. METHODS: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. RESULTS: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan-Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P-value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and progression in the cohort. CONCLUSION: Intravenous chemotherapy combined with intravesical chemotherapy offers a better oncologic outcome than the intravesical chemotherapy alone for patients with T1G3 bladder urothelial carcinoma after TURBT, and it may be considered as a new therapy strategy for T1G3 bladder cancer.

[The value of taking surgical margin specimens during transurethral resection of bladder tumor in the diagnosis and treatment of non-muscle invasive bladder cancer].

OBJECTIVE: To evaluate the value of taking surgical margin specimens during transurethral resection of bladder tumor(TURBT) in the diagnosis and treatment of non-muscle invasive bladder cancer. METHODS: The data of 356 patients with non-muscle invasive bladder cancer from June 2009 to January 2014 were analyzed retrospectively. A standardized protocol were performed during TURBT in 176 patients(surgical margin group), by taking surgical margin specimens from tumor base and 'normal'-appearing margin sites. The other 180 cases merely received general TURBT (general group). To observe the positive rate of surgical margin specimens and whether the diagnosis and treatment plan changed in the surgical margin group. Using Chi-square test to compare the recurrence and progression rates between surgical margin and general groups. To compare their recurrence-free survival time by Mann-Whitney U test. Results Of these 176 surgical margin specimens, the positive rate was 19. 3% (34/176),which consists of tumor base 11. 9% (21/176) and tumor normal-appearing margin 7. 4% (13/176). Following with urothelial carcinoma Ta stage in 1. 7% (3/176), T1 stage in 5. 7% (10/176), T2 stage in 8. 0% (14/176), carcinoma in situ (Tis) in 4. 0% (7/176). Among these 176 patients final diagnosis were changed in 10. 8% (19/176) patients due to the specimens results, and 18. 2% (32/176) patients altered their treatment plans. All 356 patients with a mean follow-up of 36. 8 months (6 to 60 months). Two groups of patients(surgical margin group vs. general group) recurrence rates respectively were 22. 2% (39/176) vs. 35. 6% (64/180), recurrence-free survival time were 33. 0 months vs. 23. 5 months and progression rates were 5. 7% (10/176) vs. 10. 6% (19/180). Compared with general group, patients who were taken additional surgical margin specimens showed significantly lower recurrence rate (χ2 = 7. 677, P = 0. 007) and longer recurrence-free survival time (U = 12 605,P = 0. 001). While the progression rate showed no statistical difference between them (χ2 = 2. 825, P = 0. 121). CONCLUSION: Taking additional surgical margin specimens during transurethral resection of bladder tumor is helpful for pathological diagnosis and the planning of further treatment.

Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.

Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.