Impact of urinary bladder cancer risk variants on prognosis and survival.
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ABSTRACT:
SUBMITTER: Selinski S
PROVIDER: S-EPMC4462828 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Impact of urinary bladder cancer risk variants on prognosis and survival.
EXCLI journal 20141128
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Project description: Not available
| S-EPMC4803017 | biostudies-literature
Project description:The transforming growth factor-beta (TGF-beta) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF-beta signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFB1 (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case-control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan-Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle-invasive tumors, we found a significant association between TGFBR1-rs868 and disease-specific mortality with an allele dosage effect (p-trend=0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of TGFBR1-rs868 with outcome should be validated in independent patient series.
| S-EPMC6896897 | biostudies-literature
Project description:ObjectivesTo investigate whether elevated urinary HAI-1, EpCAM and EGFR are independent prognostic biomarkers within non-muscle-invasive bladder cancer (NMIBC) patients, and have utility for risk stratification to facilitate treatment decisions.ResultsAfter accounting for EAU risk group in NMIBC patients, the risk of BC-specific death was 2.14 times higher (95% CI: 1.08 to 4.24) if HAI-1 was elevated and 2.04 times higher (95% CI: 1.02 to 4.07) if EpCAM was elevated. The majority of events occurred in the high-risk NMIBC group and this is where the biggest difference is seen in the survival curves when plotted for EAU risk groups separately. In MIBC patients, being elevated for any of the three biomarkers was significantly associated with BC-specific mortality after accounting for other risk factors, HR = 4.30 (95% CI: 1.85 to 10.03).Patients and methodsUrinary levels of HAI-1, EpCAM and EGFR were measured by ELISA in 683 and 175 patients with newly-diagnosed NMIBC and MIBC, respectively, recruited to the Bladder Cancer Prognosis Programme. Associations between biomarkers and progression, BC-specific mortality and all-cause mortality were evaluated using univariable and multivariable Cox regression models, adjusted for European Association of Urology (EAU) NMIBC risk groups. The upper 25% of values for each biomarker within NMIBC patients were considered as elevated. Exploratory analyses in urine from MIBC patients were also undertaken.ConclusionUrinary HAI-1 and EpCAM are prognostic biomarkers for NMIBC patients. These biomarkers have potential to guide treatment decisions for high-risk NMIBC patients. Further analyses are required to define the roles of HAI-1, EpCAM and EGFR in MIBC patients.
| S-EPMC5982738 | biostudies-literature
Project description:Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93-3.47; P = 1.87 × 10-10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers.
| S-EPMC5862341 | biostudies-literature
Project description:Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case-control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ?6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1-19, 20-29 and 30+ cigarettes per day; P(interaction) for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer.
| S-EPMC3106435 | biostudies-literature
Project description: Not available
| S-EPMC8930442 | biostudies-literature
Project description: Not available
| S-EPMC5735342 | biostudies-literature
Project description:Cancer of the urinary bladder is a neoplasm with considerable importance in veterinary medicine, given its high incidence in several domestic animal species and its life-threatening character. Bladder cancer in companion animals shows a complex and still poorly understood biopathology, and this lack of knowledge has limited therapeutic progress over the years. Even so, important advances concerning the identification of tumour markers with clinical applications at the diagnosis, prognosis and therapeutic levels have recently been made, for example, the identification of pathological BRAF mutations. Those advances are now facilitating the introduction of targeted therapies. The present review will address such advances, focusing on small animal oncology and providing the reader with an update on this field. When appropriate, comparisons will be drawn with bladder cancer in human patients, as well as with experimental models of the disease.
| S-EPMC8950778 | biostudies-literature
Project description:Bladder cancer (BC) is a common cancer but diagnostic modalities, such as cystoscopy and urinary cytology, have limitations. Here, high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOFMS) was used to profile urine metabolites of 138 patients with BC and 121 control subjects (69 healthy people and 52 patients with hematuria due to non-malignant diseases). Multivariate statistical analysis revealed that the cancer group could be clearly distinguished from the control groups on the basis of their metabolomic profiles, even when the hematuric control group was included. Patients with muscle-invasive BC could also be distinguished from patients with non-muscle-invasive BC on the basis of their metabolomic profiles. Successive analyses identified 12 differential metabolites that contributed to the distinction between the BC and control groups, and many of them turned out to be involved in glycolysis and betaoxidation. The association of these metabolites with cancer was corroborated by microarray results showing that carnitine transferase and pyruvate dehydrogenase complex expressions are significantly altered in cancer groups. In terms of clinical applicability, the differentiation model diagnosed BC with a sensitivity and specificity of 91.3% and 92.5%, respectively, and comparable results were obtained by receiver operating characteristic analysis (AUC = 0.937). Multivariate regression also suggested that the metabolomic profile correlates with cancer-specific survival time. The excellent performance and simplicity of this metabolomics-based approach suggests that it has the potential to augment or even replace the current modalities for BC diagnosis.
| S-EPMC4039236 | biostudies-literature
Project description:BackgroundBladder cancer is the tenth most common cancer worldwide. Valuable biomarkers in the field of diagnostic bladder cancer are urgently required.MethodHere, the gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA), GSE13507, GSE32894, and Mariathasan et al. Five prognostic genes were identified by the univariate, robust, and multivariate Cox's regression and were used to develop a prognosis-related model. The Kaplan-Meier survival curves and receiver operating characteristics were used to evaluate the model's effectiveness. The potential biological functions of the selected genes were analyzed using CIBERSORT and ESTIMATE algorithms. Cancer Therapeutics Response Portal (CTRP) and PRISM datasets were used to identify drugs with high sensitivity. Subsequently, using the bladder cancer (BLCA) cell lines, the role of TNFRSF14 was determined by Western blotting, cell proliferation assay, and 5-ethynyl-20-deoxyuridine assay.ResultsGSDMB, CLEC2D, APOL2, TNFRSF14, and GBP2 were selected as prognostic genes in bladder cancer patients. The model's irreplaceable reliability was validated by the training and validation cohorts. CD8+ T cells were highly infiltrated in the high-TNFRSF14-expression group, and M2 macrophages were the opposite. Higher expression of TNFRSF14 was associated with higher expression levels of LCK, interferon, MHC-I, and MHC-II, while risk score was the opposite. Many compounds with higher sensitivity for treating bladder cancer patients in the low-TNFRSF14-expression group were identified, with obatoclax being a potential drug most likely to treat patients in the low-TNFRSF14-expression group. Finally, the proliferation of BLCA cell lines was increased in the TNFRSF14-reduced group, and the differential expression was identified. TNFRSF14 plays a role in bladder cancer progression through the Wnt/β-catenin-dependent pathway. TNFRSF14 is a potential protective biomarker involved in cell proliferation in BLCA.ConclusionWe conducted a study to establish a 5-gene score model, providing reliable prediction for the outcome of bladder cancer patients and therapeutic drugs to individualize therapy. Our findings provide a signature that might help determine the optimal treatment for individual patients with bladder cancer.
| S-EPMC8545590 | biostudies-literature