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The aim of the study is to evaluate mRNA/protein expression of zinc finger protein 165 (ZNF165) in transitional cell carcinomas (TCCs) of urinary bladder and correlate its expression with the clinicopathological characteristics of patients. In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were utilized to evaluate mRNA/protein expression of ZNF165 in TCC. Independent Student's t test, ANOVA and Chi-square (χ²) were used to analyze the data statistically. We observed overexpression of ZNF165 mRNA in testis and majority (59.2%) of TCC patients. ZNF165 mRNA expression was also detected in adjacent noncancerous tissues (ANCTs) and some other normal tissues. Relative mean fold expression of ZNF165 mRNA was found to be significantly (p < 0.01) higher in muscle-invasive bladder cancer (MIBC) as compared to non-muscle-invasive bladder cancer (NMIBC) patients. (12.11 ± 9.57 vs. 5.72 ± 2.61, p = 0.009). ZNF165 protein expression was demonstrated on archival formalin-fixed, paraffin-embedded (FFPE) bladder tissues using IHC and nuclear staining pattern was detected. No significant difference was observed in protein expression of ZNF165 between the two groups (NMIBC and MIBC patients) (61.1% vs. 55.2%, p = 0.629). No significant protein expression of ZNF165 was observed among ANCTs and benign prostatic hyperplasia (BPH) used as control. Our study results suggest that ZNF165 mRNA/protein expression was observed in TCC of human urinary bladder and might be used as a novel diagnostic biomarker and as well a vaccine target in development of urinary bladder cancer specific immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Matrix metalloproteinases (MMPs) are expressed in melanocytes and their overexpression has been linked to tumor development, progression, and metastasis. At the genetic level, following functional promoter polymorphisms are known to modify the gene transcription: −1306 C > T, −735 C > T in MMP2, and 799 C > T in MMP8 gene. Hence we hypothesize that functional polymorphisms in the 2 MMP SNPs in promoter region may modulate the risk for bladder cancer (BC) progression in North Indian population. Materials and methods: Genotyping for these polymorphisms were done in a group of 200 BC and 200 age matched, similar ethnicity unrelated healthy controls using PCR-based methods. Two-sided χ2, Cox-regression was utilized to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known BC confounders such as age and gender. Survival analysis was done using the Kaplan-Meier method and differences in survival were assessed using the log rank test. Results: Individuals with MMP2 (−1306) TT genotype as well as T allele were at higher risk of BC (P, 0.042; OR, 2.85; P, 0.001; OR, 1.76). This effect was even more apparent in case of CT+TT (P < 0.001; OR, 2.61). In MMP2 (735), CT+TT demonstrated significant risk (P, 0.034; OR, 1.66). In MMP8 (799), reduced risk was observed with TT genotype (P, 0.006; OR, 0.27). Haplotype analysis showed that individuals with haplotype 735C-1306T and 735T-1306C were at 1.9- and 1.5-fold higher risk. MMP2 −1306CC in combination with MMP8 799CT genotype showed protective effect. The genotype CT and CT+TT of MMP2 1306C > T were associated with high risk of recurrence in BCG treated patients (HR, 4.32; P, 0.006 and HR, 2.06; P, 0.047) thus showing reduced recurrence free survival (CT+TT/CC = 34/45 months; log rank P, 0.039). Conclusion: Our data suggested that variant allele of MMP2 1306C > T was associated with high risk of tumor recurrence and reduced recurrence free survival in superficial BC patients. [Copyright &y& Elsevier]

Background and Aims: Impairment of the immune system may contribute to the risk for having cancer as Toll-like receptors are important for innate immunity. We examined the association between candidate disease-susceptibility polymorphisms in the single nucleotide polymorphism (SNPs) like TLR2 (−196 to−174del), TLR3 (C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes in patients with bladder cancer in a North Indian population. Methods: SNPs were comprised of TLR2 (−196 to −174 Del), TLR3(C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes. Allelic and genotypic frequencies of these TLRs SNP from histopathologically confirmed patients of bladder cancer (n = 200) and unrelated healthy controls of similar ethnicity (n = 200) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Results: In TLR2 I/D gene polymorphism, the combination of ID+DD showed a significant 3-fold increased risk (p = 0.001). TLR2 with heterozygous genotype ID showed a 3-fold risk and combination of heterozygous and variant genotype (ID+DD) also showed a 5-fold risk with tumor stage/grade of patients with bladder cancer. The other genotypes of TLR3, 4 and 9 did not exhibit any significant association with bladder cancer risk. Conclusions: Our results suggested the involvement of TLR2 (−196 to−174 del) in bladder cancer susceptibility; however, TLR3, 4 and 9 genes were not associated with risk of bladder cancer, implicating that polymorphisms in these tested TLRs genes are not likely to be associated with increased risk for developing bladder cancer. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for the etiology of bladder cancer. [Copyright &y& Elsevier]

p53 is a major orchestrator of cellular response to a broad array of stress types by regulating apoptosis, cell cycle arrest, etc. A few polymorphic sites, one at codon72 of exon4, intron3 16bpdel/ins, intron6G>A have been studied with regard to Bladder cancer (BC) risk in North Indians. Genotypes were assessed in hospital-based case-control study comprising of 200BC cases, 265healthy controls. After extraction of genomic DNA from blood, genotyping was done using PCR Restriction Fragment Length Polymorphism. Individuals with p53R72P G>C, CC genotype demonstrated marginally reduced risk of BC (p=0.053, OR=0.29, 95% 16bp-ins/del, [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Perturbed apoptosis due to missense alterations in candidate tumor suppressor gene Death receptor 4 (DR4) and in caspases (Casp) lead to deregulated cell proliferation and cancer predisposition. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. To test our proposal we examined whether six single nucleotide polymorphisms (SNPs) of the DR4 and Casp3, 5 genes contrive the risk of bladder cancer (BC) in a North Indian population. Materials and methods: Genotyping was performed in 200 BC patients and 225 controls by Allele-specific PCR and by polymerase chain reaction-restriction fragment length polymorphism. Results: In DR4 Arg141His, BC patients having AA genotype (p = 0.036; OR = 2.51. In Casp5Leu13Phe G > C, significant association was observed with GC (p = 0.025; OR = 1.78) and also in GC + CC (p = 0.026; OR = 1.68). C allele carriers in Casp5Ala90Thr T > C showed low risk of BC (p = 0.036; OR = 0.83). While in Casp3 G > A, AG (p = 0.003; OR = 2.11), GG (p = 0.050; OR = 2.18), G allele (p < 0.001; OR = 1.85) and its carrier AG + GG (p = 0.001; OR = 2.12) have shown significant BC risk. Significant association between DR4 Ala228Glu polymorphism and smoking was observed in BC risk. Haplotype analysis demonstrated that DR4 (Thr209Arg–Arg141His–Ala228Glu) C-G-C is associated with 1.8 folds (OR = 1.85; p = 0.033) risk. GG genotype of Casp3 G > A polymorphism showed increased risk of recurrence (p = 0.009; HR = 5.20). Conclusion: This study provided new support for the association of DR4 and Casp3, 5 in BC development, the tumorigenic effect of which was observed to be more enhanced in case of smoking exposure. [Copyright &y& Elsevier]

Matrix metalloproteinases (MMPs) contribute to tumor invasion and microenvironment, hence are associated with bladder cancer risk. We therefore, tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC) and whether smoke exposure modifies this risk. Genotyping was performed in 200 BC patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and MMP7-181 GG genotype were associated with increased risk of BC (p < 0.001; OR, 3.04; 95% CI- 1.71–5.39 and p, 0.005; OR, 2.38; 95% CI- 1.30–4.34) respectively. Smokers in BC patients showed significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI- 1.40–7.31 and p, 0.009; OR, 2.85; 95% CI- 1.30–6.23 respectively). Haplotype analysis too revealed significant association with G/2G of MMP1-519-1607 (p< 0.001; OR, 2.62; 95% CI- 1.68–4.09). The 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607 showed a protective effect and high recurrence free survival in Bacillus Calmette-Guérin (BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our data suggested that MMP1-1607 2G and MMP7-181 G allele were associated with high risk of BC, which was quite evident amongst smokers too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607. This study provided new support for the association of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect of which was observed to be more enhanced in case of tobacco exposure. [ABSTRACT FROM AUTHOR]