• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3543-3549
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• 2015

Background: Bladder cancer is one of the most common cancers worldwide. Gene expression profiling using microarray technologies improves the understanding of cancer biology. The aim of this study was to determine the gene expression profile in Egyptian bladder cancer patients. Materials and Methods: Samples from 29 human bladder cancers and adjacent non-neoplastic tissues were analyzed by cDNA microarray, with hierarchical clustering and multidimensional analysis. Results: Five hundred and sixteen genes were differentially expressed of which SOS1, HDAC2, PLXNC1, GTSE1, ULK2, IRS2, ABCA12, TOP3A, HES1, and SRP68 genes were involved in 33 different pathways. The most frequently detected genes were: SOS1 in 20 different pathways; HDAC2 in 5 different pathways; IRS2 in 3 different pathways. There were 388 down-regulated genes. PLCB2 was involved in 11 different pathways, MDM2 in 9 pathways, FZD4 in 5 pathways, p15 and FGF12 in 4 pathways, POLE2 in 3 pathways, and MCM4 and POLR2E in 2 pathways. Thirty genes showed significant differences between transitional cell cancer (TCC) and squamous cell cancer (SCC) samples. Unsupervised cluster analysis of DNA microarray data revealed a clear distinction between low and high grade tumors. In addition 26 genes showed significant differences between low and high tumor stages, including fragile histidine triad, Ras and sialyltransferase 8 (alpha) and 16 showed significant differences between low and high tumor grades, like methionine adenosyl transferase II, beta. Conclusions: The present study identified some genes, that can be used as molecular biomarkers or target genes in Egyptian bladder cancer patients.

• Journal of Preventive Medicine and Public Health
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• v.31 no.2 s.61
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• pp.275-284
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• 1998

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which .educe the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTMI) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% to. the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity($\chi^2_{trend}=1.18$, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls ($\chi^2=5.21$, P-value<0.05), and the odds ratio (95% CI) was 2.23 (1.12 - 4.56). GSTT1 deletion, the .ate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history turned out to be insignificant as a risk factor of bladder cancer (OR=1.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: 1.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7249-7254
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• 2015

Background: Previous studies evaluated associations between the CYP1A2 rs762551 polymorphism and bladder cancer risk. However, the results were inconsistent. We therefore performed a meta-analysis of the published case-control studies to assess in detail the association between CYP1A2 rs762551 polymorphism and bladder cancer risk. Materials and Methods: PubMed, Embase and Web of Science were searched to identify relevant studies and the pooled odds ratio (OR) and 95 % confidence interval (95%CI) were calculated. Results: A total of seven articles including 3,013 cases and 2,771 controls were finally included. Overall, a significant association was found between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for CC vs AA (OR=0.82, 95% CI=0.69~0.99), but no significant associations were found for the other three models (AC vs AA: OR=0.91, 95% CI=0.81~1.02; the dominant model: OR=0.90, 95% CI=0.80~1.00; the recessive model: OR=0.84, 95% CI =0.72~1.00). In the subgroup analysis by ethnicity, we detected significant associations between the CYP1A2 rs762551 polymorphism and bladder cancer susceptibility for GA vs GG (OR = 0.78, 95% CI =0.64~0.96) and for the recessive model (OR=0.80, 95% CI=0.66~0.96) in Caucasians, but not for Asians. Conclusions: The results from the meta-analysis suggested that the CYP1A2 rs762551 polymorphism is a protective factor for bladder cancer, especially in Caucasians.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3117-3121
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• 2013

Objective: Previous epidemiologic studies demonstrated that obesity might associated with the risk of bladder cancer. However, many of the actual association findings remained conflicting. To better clarify and provide a comprehensive summary of the correlation between obesity and bladder cancer risk, we conducted a meta-analysis to summarize results of studies on the issue. Stratified analyses were also performed on potential variables and characteristics. Methods: Studies were identified by searching in PubMed and Wanfang databases, covering all the papers published from their inception to March 10, 2013. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated by either random-effect or fixed-effect models. Results: A total of 11 cohort studies were included in our meta-analysis, which showed that obesity was associated with an increased risk for bladder cancer in all subjects (RR=1.10, 95% CI=1.06-1.16; p=0.215 for heterogeneity; $I^2$=24.0%). Among the 9 studies that controlled for cigarette smoking, the pooled RR was 1.09 (95% CI 1.01-1.17; p=0.131 for heterogeneity; $I^2$=35.9%). No significant publication bias was detected (p = 0.244 for Egger's regression asymmetry test). Conclusions: Our results support the conclusion that obesity is associated with the increased risk of bladder cancer. Further research is needed to generate a better understanding of the correlation and to provide more convincing evidence for clinical intervention in the prevention of bladder cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3847-3850
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• 2013

The three homologous members of the p160 SRC family (SRC-1, SRC-2 and SRC-3) mediate the transcriptional functions of nuclear receptors and other transcription factors, and are the most studied of all the transcriptional co-activators. Recent work has indicated that the SRC-3 gene is subject to amplification and overexpression in various human cancers. Some of the molecular mechanisms responsible for SRC overexpression, along with the mechanisms by which SRC-3 promotes breast and prostate cancer cell proliferation and survival, have been identified. However, the function of SRC-3 in bladder cancer remains poorly understood. In the present study, our results indicate that overexpression of SRC-3 promotes bladder cancer cell proliferation whereas knockdown of SRC-3 results in inhibition. At the molecular level, we further established that CXCR4 is a transcriptional target of SRC-3. Therefore, our study first identified that SRC-3 plays a critical role in the bladder cancer, which may be a target beneficial for its prevention and treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.381-384
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• 2014

Background: Evidence indicates that Dickkopf-1 (DKK-1) levels may be a biomarker for cancer risk. The aim of this study was to assess DKK-1 and its correlation with clinic-pathological features in patients with bladder cancer. Materials and Methods: DKK-1 levels were determined in serum samples from 90 patients with bladder cancer before transurethral tumor resection. The concentrations of DKK-1 were determined by using enzyme linked immune-sorbent assay (ELISA). Results: Elevated preoperative DKK-1 levels were associated with tumor stage (p<0.001), grade (p<0.001) and histological grade (p<0.001). Conclusions: The results of our study demonstrated that the level of serum DKK-1 is correlated with both disease progression and increase in the tumor grade. Preoperative serum DKK-1 elevation may thus represent a novel marker for the determination of bladder cancer and the detection of patients with a likely poor clinical outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3839-3841
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• 2015

Background: This pooled analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic bladder cancer as salvage chemotherapy. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with bladder cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In pemetrexed based regimens, 3 clinical studies which including 105 patients with advanced transitional cell cancer of the urothelium were considered eligible for inclusion. Pooled analysis suggested that, in all patients, pooled RR was 26.7% (28/105) for pemetrexed based regimens. Major adverse effects were neutropenia, anorexia, fatigue, and anemia in pemetrexed based treatment. Two treatment related deaths occurred with pemetrexed based treatment. Conclusion: This pooled analysis suggests that pemetrexed based regimens are associated with mild activity and good tolerability in treating patients with metastatic bladder cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3925-3929
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• 2013

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

• The Korean Journal of Cytopathology
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• v.7 no.2
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• pp.144-150
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• 1996

Although bladder cancers are very common, little is known about their molecular pathogenesis. It is known that p53 alteration is found in about 60% of muscle-invasive bladder cancer, necessiating aggressive therapy and poor outcome. We examined the nuclear expression of p53 protein, using D07 monoclonal antibody in the urine samples from 31 patients with transitional cell carcinoma of the bladder to investigate the correlation of p53 overexpression with histologic grades and depth of invasion. The positive rate of p53 protein was 27% in superficial bladder tumor, but increased up to 71% in the invasive bladder carcinomas. The overexpression of p53 protein increased according to Mostofi grading system from 18% in grade I, 45% in grade II, and up to 100% in grade III. The p53 expression tended to be higher in the invasive and high grade bladder cancers than in the superficial and low grade ones(p<0.05). These results suggest that immunohistochemical analysis of the urine specimen in the bladder cancer patients could be a useful method of screening for the presence of p53 mutant protein. The mutant p53 protein expression may be an indicator of bladder cancer with more proliferative potential and/or aggressive biologic behavior.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.105-108
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• 2016

Background: Epidemiological evidence indicates that individuals with diabetes mellitus (DM) may have a modestly increased risk of bladder cancer. In the present study, we aimed to show any association between DM and risk of metastasis in patients with non-muscle-invasive bladder cancer (NMIBC). Materials and Methods: We retrospectively analyzed 698 patients between January 2007 and December 2014 who were diagnosed with and underwent transurethral resection of bladder tumors (TUR-BT). Comparisons of means was conducted by independent samples t test, and relations between categorical variables were investigated by non-parametric chi-square test. A p value of 0.05 was accepted as statistically significant in comparisons. Results: We analyzed 418 patients with non muscle invasive bladder cancer. 123 of whom were diabetic and 295 non-diabetic. In diabetic patients, 13 were N1 stage and 11 M1 stage. When compared with non diabetic patients that was statistically significant (p<0.001). TNM stages were more advanced in diabetic patients (p<0.001), but concurrent CIS (p=0.1) and squamous metaplasia did not significantly differ between diabetic and non-diabetic cases (p=1). Conclusions: Diabetic patients with non-muscle-invasive bladder cancer may suffer metastases earlier than expected although they are non invasive. Therefore such patients must be followed-up carefully and early cystectomy decision may be necessary. Further prospective studies with more patients are needed to confirm these findings.