Bladder Cancer
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Bladder cancer is a disease in which malignant cells arise in the bladder. Symptoms can include blood in the urine, pain during urination, increased frequency of passing urine, or feeling the need to urinate but with nothing coming out. The bulk of bladder cancers are histlogically classed as transitional cell carcinomas which arise in the uroepithelium (lining of the bladder). Other types include squamous cell carcinomas, and adenocarcinomas. Treatment will depend on how far the tumour has invaded the surrounding tissues, and if it has spread to other parts of the body. World-wide about 260,000 people are diagnosed with bladder cancer each year.

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Latest Research Publications
Molecular Biology of Bladder Cancer
Urinary System Cancers

Information Patients and the Public (14 links)


Information for Health Professionals / Researchers (8 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Zhuo W, Zhang L, Cai L, et al.
XRCC1 Arg399Gln polymorphism and bladder cancer risk: updated meta-analyses based on 5767 cases and 6919 controls.
Exp Biol Med (Maywood). 2013; 238(1):66-76 [PubMed]
Previous reports implicate XRCC1 Arg399Gln polymorphism as a possible risk factor for several cancers. Published meta-analyses have been conducted on the association of XRCC1 Arg399Gln polymorphism with susceptibility to bladder cancer, and have generated conflicting results. The present study aimed to derive a more precise estimation of the relationship. Updated meta-analyses assessing the association of XRCC1 Arg399Gln polymorphism with bladder cancer were conducted and subgroup analyses on ethnicity, smoking status and source of controls were further performed. Eligible studies were identified for the period up to May 2012. A total of 19 case-control studies comprising 5767 cases and 6919 controls were lastly selected for analysis. The overall data failed to indicate significant associations between XRCC1 Arg399Gln polymorphism and bladder cancer risk (Gln/Gln versus Arg/Arg: odds ratio (OR) = 0.97; 95% CI = 0.85-1.10; dominant model: OR = 1.02; 95% CI = 0.94-1.09; recessive model: OR = 0.95; 95% CI = 0.84-1.07). In subgroup analyses stratified by ethnicity, smoking status and source of controls, respectively, similar results were obtained. In conclusion, the results of the present study suggest that XRCC1 Arg399Gln polymorphism might not modify the susceptibility to bladder cancer. Further large and well-designed studies are needed to confirm this conclusion.


Buchner A, May M, Burger M, et al.
Prediction of outcome in patients with urothelial carcinoma of the bladder following radical cystectomy using artificial neural networks.
Eur J Surg Oncol. 2013; 39(4):372-9 [PubMed]
AIM: The outcome of patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) shows remarkable variability. We evaluated the ability of artificial neural networks (ANN) to perform risk stratification in UCB patients based on common parameters available at the time of RC.
METHODS: Data from 2111 UCB patients that underwent RC in eight centers were analysed; the median follow-up was 30 months (IQR: 12-60). Age, gender, tumour stage and grade (TURB/RC), carcinoma in situ (TURB/RC), lymph node status, and lymphovascular invasion were used as input data for the ANN. Endpoints were tumour recurrence, cancer-specific mortality (CSM) and all-cause death (ACD). Additionally, the predictive accuracies (PA) of the ANNs were compared with the PA of Cox proportional hazards regression models.
RESULTS: The recurrence-, CSM-, and ACD- rates after 5 years were 36%, 33%, and 46%, respectively. The best ANN had 74%, 76% and 69% accuracy for tumour recurrence, CSM and ACD, respectively. Lymph node status was one of the most important factors for the network's decision. The PA of the ANNs for recurrence, CSM and ACD were improved by 1.6% (p = 0.247), 4.7% (p < 0.001) and 3.5% (p = 0.007), respectively, in comparison to the Cox models.
CONCLUSIONS: ANN predicted tumour recurrence, CSM, and ACD in UCB patients after RC with reasonable accuracy. In this study, ANN significantly outperformed the Cox models regarding prediction of CSM and ACD using the same patients and variables. ANNs are a promising approach for individual risk stratification and may optimize individual treatment planning.


Zhong M, Gersbach E, Rohan SM, Yang XJ
Primary adenocarcinoma of the urinary bladder: differential diagnosis and clinical relevance.
Arch Pathol Lab Med. 2013; 137(3):371-81 [PubMed]
CONTEXT: Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign glandular lesions to primary and secondary malignancies. Common benign bladder lesions that exhibit glandular differentiation include cystitis cystica, cystitis glandularis, von Brunn nests, nephrogenic adenoma, intestinal metaplasia, urachal remnant, endometriosis, and prostatic-type polyp. The World Health Organization defines primary adenocarcinoma of the bladder as an epithelial malignancy with pure glandular differentiation without evidence of typical urothelial carcinoma. Malignant lesions that should be included in the differential diagnosis of a primary adenocarcinoma of the bladder include noninvasive and invasive urothelial carcinoma with glandular differentiation and secondary malignancies involving the bladder by direct extension or metastasis. The recognition and distinction of these different entities may be a challenge for pathologists, but they are of great clinical importance.
OBJECTIVE: To review features of primary bladder adenocarcinoma as well as those entities that need to be differentiated from primary bladder adenocarcinoma, with emphasis on clinical findings, pathologic characteristics, and immunoprofiles.
DATA SOURCES: Selected original articles published in the PubMed service of the US National Library of Medicine.
CONCLUSIONS: The accurate diagnosis of adenocarcinoma of the urinary bladder is important and challenging. It has to prompt an extensive clinical workup to rule out other glandular lesions in the urinary bladder, especially the possibility of secondary involvement of the bladder by an adenocarcinoma from a different site.


Montanari E, de la Rosette J, Longo F, et al.
Narrow-band imaging (NBI) and white light (WLI) transurethral resection of the bladder in the treatment of non-muscle-invasive bladder cancer.
Arch Ital Urol Androl. 2012; 84(4):179-83 [PubMed]
OBJECTIVE: Narrow-band imaging (NBI) is an optical image enhancement technology Summary that narrows the bandwidth of the light output from the endoscopy system to 415 nm and 540 nm. The aim of the present study is to evaluate the feasibility of NBI transurethral resection of the bladder (TURB NBI) compared to in White Light (TURB WLI) (Feasibility study) and the recurrence rate at the 1-year follow-up in patients treated for non-muscle-invasive bladder cancer (NMIBC) (recurrence study).
METHODS: A total of 92 patients with a suspicion of primary or recurrent bladder cancer were prospectively enrolled in our study. Forty-five were consecutively enrolled to undergo WLI TURB and 47 consecutively to undergo NBI TURB. All patients underwent routine follow-up with flexible WLI cystoscopy every 3 months during the first year and every 6 months during the second year, supplemented by urine examination, urine culture, and bladder washout cytology.
RESULTS: Type I-II complications were reported in 12 patients in the NBI group (25%) and in 10 patients in the WLI group (22%). Patients with High Grade NMIBC who underwent a second look WLI TURB had residual disease in 33% of NBI group and in 43% of WLI group.The recurrence rate at one year follow-up was 35% in NBI group and 50% in WLI group. No statistic significance can be issued for the clinical differences observed.
CONCLUSIONS: TURB performed entirely by the NBI technique is feasible and safe. It guarantees a complete and rapid resection of good quality from a pathological point of view. Moreover, the technique is relatively inexpensive with respect to other methods proposed to enhance the detection rate, for which data on operative endoscopy are lacking. In our clinical experience, even if not statistically significant, NBI TURB reduces at one year follow up the recurrence rate of bladder NMI tumours when compared to WLI TURB (35% vs. 50%). Other larger, randomized, prospective trials with longer follow-up periods are required to confirm our outcomes.


Ali-El-Dein B, Mosbah A, Osman Y, et al.
Preservation of the internal genital organs during radical cystectomy in selected women with bladder cancer: a report on 15 cases with long term follow-up.
Eur J Surg Oncol. 2013; 39(4):358-64 [PubMed]
PURPOSE: To prospectively present the technique, functional and oncological outcome of internal genitalia sparing cystectomy for bladder cancer in 15 selected women.
PATIENTS AND METHODS: Between January 1995 and December 2010, 305 women underwent orthotopic neobladder after radical cystectomy. Of these, 15 cases with a mean age of 42 years underwent genitalia sparing. Inclusion criteria included stage (T2b N0 Mo or less, as assessed preoperatively, unifocal tumors away from the trigone, sexually active young women and internal genitalia free of tumor. Cystectomy with preservation of the uterus, vagina and ovaries and Hautmann neobladder were performed. Oncological, functional, urodynamic and sexual outcome using Female Sexual Function Index (FSFI) were evaluated.
RESULTS: Definitive histopathology showed advanced stage not recognized preoperatively in 2 patients, who developed local recurrence and bony metastasis after 3-4 months. A third patient developed bony metastasis after 15 months. No recurrence developed in the retained genital organs. The remaining 12 patients remained free of disease with a mean follow-up of 70 months. Among women eligible for functional evaluation, daytime and nighttime continence were achieved in 13/13 (100%) and 12/13 (92)%, respectively. Chronic urinary retention was not noted. The urodynamic parameters were comparable to those in other patients without genital preservation. Sexual function (FSFI) was better in these patients than in others without genital preservation.
CONCLUSIONS: Genital sparing cystectomy for bladder cancer is feasible in selected women. It provides a good functional outcome, better sexual function and the potential for fertility preservation. So far, the oncological outcome is favorable.


Compérat E, Jacquet SF, Varinot J, et al.
Different subtypes of carcinoma in situ of the bladder do not have a different prognosis.
Virchows Arch. 2013; 462(3):343-8 [PubMed]
Urothelial carcinoma in situ (CIS) is a high-grade lesion with different subtypes (large cell pleomorphic (LCP), large cell nonpleomorphic (LC), small cell and clinging (CL)). We explored the frequency of different subtypes in primary CIS and compared different patterns with outcome. We explored whether subtyping of CIS leads to a change in therapy and/or follow-up and should be formally reported. We included 39 patients with a primary CIS and divided them into two groups: one with LPC/LG and one with CL elements. Other subtypes did not exist or occurred only as a mixture. Patient age ranged from 36 to 80 years (mean, 63 years). Twenty had a primary CIS with one single subtype. LCP was predominant with 16 (41 %) cases; the second most important subtype was the CL with four (10 %) cases. Mean follow-up was 26.4 months, (range, 4-100 months). Thirteen patients developed a ≥ pT2 carcinoma. When progression of the different subtypes was examined, no statistical significance was found between mixed forms (p = 0.9437) nor between pure forms (p = 0.744 and p = 0.5955, respectively). Pathologists need not include different subtypes of primary CIS in their report as there is no difference in patient outcomes. It is important to recognize all different subtypes as CIS for best patient treatment.


Lah K, Desai D, Hadway P, et al.
Primary vesical clear cell adenocarcinoma arising in endometriosis: a rare case of mullerian origin.
Anticancer Res. 2013; 33(2):615-7 [PubMed]
Clear cell adenocarcinoma arising out of endometriosis of the urinary bladder is a rare entity. The published literature has a dearth of information about this entity and its histogenesis. In the present case review we present a 59-year-old patient who was treated with robotic anterior pelvic exenteration and ileal conduit. The initial biopsy of bladder tumour purported a high-grade urothelial carcinoma, however the final specimen revealed a clear cell adenocarcinoma arising in endometriosis without any urothelial cancer. Early case reports refer to these lesions as mesonephric or mesonephroid adenocarcinomas but the current WHO nomenclature classifies them under non-urothelial epithelial neoplasms as clear cell adenocarcinomas. Here, we review the literature and discuss their origins.


Cheng D, Liang B, Li Y
Clinical value of vascular endothelial growth factor and endostatin in urine for diagnosis of bladder cancer.
Tumori. 2012; 98(6):762-7 [PubMed]
AIMS AND BACKGROUND: The aim of the study was to determine whether urinary VEGF and endostatin predict the presence of bladder cancer, and whether these noninvasive biomarkers provide clinically useful information in the bladder cancer patient as well.
METHODS AND STUDY DESIGN: Voided urine samples were collected from 239 patients (109 bladder cancers, 81 urological disorders, 49 healthy controls). The urine levels of VEGF and endostatin were determined with the sandwich enzyme immunoassay technique.
RESULTS: Urine levels of VEGF and endostatin were higher in patients with bladder cancer than those in patients with urological disorders and healthy controls (P <0.01). The difference between patients with urological disorder and healthy controls was significant only for VEGF (P <0.01). Urine level of VEGF was related to the tumor grade, and urine level of endostatin was related to tumor stage, tumor size and tumor number (P <0.05). The optimal cutoffs for VEGF and endostatin were calculated by the ROC curves as 860 pg/ml for VEGF, and 350 pg/ml for endostatin. The five-year survival rate was 60.0% in patients with low level of endostatin (<350 pg/ml) and 7.69% in patients with high level of endostatin (≥350 pg/ml) in the bladder cancer group. Patients with a high level of endostatin had a shorter survival time, whereas patients with a low level of endostatin had a longer survival time (P <0.05).
CONCLUSIONS: Urine levels of VEGF and endostatin may be a clinically useful aid in the diagnosis of bladder cancer, and endostatin but not VEGF is a supplementary prognostic marker for predicting tumor progression.


Peiris AN, Bailey BA, Manning T
Relationship of vitamin D monitoring and status to bladder cancer survival in veterans.
South Med J. 2013; 106(2):126-30 [PubMed]
OBJECTIVES: Veterans of the armed forces, like most population groups, have a high prevalence of vitamin D deficiency, which may be associated with adverse outcomes in several types of cancer. Ultraviolet irradiation is inversely linked with the risk of bladder cancer, presumably through enhanced vitamin D synthesis. We hypothesized that variations in vitamin D status and monitoring predict adverse outcomes in bladder cancer among veterans.
METHODS: A retrospective analysis of data in the Veterans Integrated Service Network-9 (southeastern United States) was performed for patients diagnosed between October 1, 1999 and February 29, 2008. Age, tobacco exposure, body mass index, and latitude and seasonality of sampling were included as variables in addition to serum vitamin 25(OH)D levels.
RESULTS: Monitoring of vitamin D and vitamin D levels and status were closely linked to survival in bladder cancer. Both the chances of survival and longevity improved with enhanced vitamin D status and monitoring. Veterans with bladder cancer had better outcomes if the initial vitamin D level was higher and had more monitoring of the vitamin. Initial vitamin D levels were more strongly related to outcomes than follow-up levels. The link between vitamin D and outcomes remained after adjusting for background variables such as age, body mass index, latitude, seasonality, and tobacco exposure.
CONCLUSIONS: Findings suggest that adequate vitamin D levels early in the course of the disease provide the best opportunity to improve outcomes. Ensuring that veterans with bladder cancer have adequate vitamin D reserves with appropriate monitoring may play a role in improving outcomes in bladder cancer.


Redelman-Sidi G, Iyer G, Solit DB, Glickman MS
Oncogenic activation of Pak1-dependent pathway of macropinocytosis determines BCG entry into bladder cancer cells.
Cancer Res. 2013; 73(3):1156-67 [PubMed]
Bacille Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that is used widely as a vaccine for tuberculosis and is used as an effective treatment for superficial bladder carcinoma. Despite being the most successful cancer biotherapy, its mechanism of action and response determinants remain obscure. Here, we establish a model system to analyze BCG interaction with bladder cancer cells, using it to show that these cells vary dramatically in their susceptibility to BCG infection. Unexpectedly, the uptake of BCG by bladder cancer cells occurs by macropinocytosis rather than phagocytosis. BCG entry into bladder cancer cells relied upon Rac1, Cdc42, and their effector kinase Pak1. The difference in susceptibility between BCG-permissive and -resistant bladder cancer cells was due to oncogenic activation of signaling pathways that activate macropinocytosis, with phosphoinositide 3-kinase inhibitor activation stimulating BCG uptake independently of Akt. Similarly, activated Ras strongly activated Pak1-dependent uptake of BCG. These results reveal that oncogenic activation of macropinocytosis determines BCG uptake by bladder cancer cells, implying that tumor responsiveness to BCG may be governed by the specific mutations present in the treated cancer cell.


Meijer RP, Nieuwenhuijzen JA, Meinhardt W, et al.
Response to induction chemotherapy and surgery in non-organ confined bladder cancer: a single institution experience.
Eur J Surg Oncol. 2013; 39(4):365-71 [PubMed]
AIM: To evaluate the outcome of patients with locally advanced muscle-invasive and/or lymph node positive bladder cancer treated with induction chemotherapy and additional surgery.
METHODS: All patients who were treated with induction chemotherapy in our institution between 1990 and 2010, were retrospectively evaluated using an institutional database. Induction chemotherapy consisted of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC), or a combination of gemcitabine with either cisplatin or carboplatin (GC).
RESULTS: In total 152 patients were identified, with a mean age of 59 years (range 31-76). One hundred and seven patients (70.4%) received MVAC, 35 patients received GC (23.0%) and 10 patients received GC after initial treatment with MVAC (6.6%). Median follow-up was 68 months (range 4-187 months). Overall 125 patients (82.2%) underwent cystectomy, whereas 12 patients (7.9%) received radiotherapy. Fifteen patients had no local treatment. Median overall survival was 18 months (95%CI 15-23 months). In 37.5% of patients with complete clinical response, residual disease was found at surgery (positive predictive value, PPV 62.5%). Complete pathological response was seen in 26.3% of patients, with a 5 year overall survival (OS) estimate of 54% (39%-74%). For patients with persisting node positive disease after induction chemotherapy and surgery OS was significantly worse (p < 0.0001).
CONCLUSIONS: Complete clinical and/or pathological response to induction chemotherapy results in a significant survival benefit. The accuracy of the current clinical response evaluation after induction chemotherapy is limited. Although surgery may be important for staging and prognostic purposes, its role is unclear in node positive disease after induction chemotherapy.


Kuru TH, Roethke MC, Nyarangi-Dix J, et al.
Pediatric case report on magnetic resonance imaging/transrectal ultrasound-fusion biopsy of rhabdomyosarcoma of the bladder/prostate: a new tool to reduce therapy-associated morbidity?
Urology. 2013; 81(2):417-20 [PubMed]
Rhabdomyosarcomas are the most common soft tissue sarcomas in children. Here we present management of an 18-month-old boy with metastatic rhabdomyosarcoma of the bladder/prostate. After radiochemotherapy, high-spatial-resolution 3-Tesla multiparametric magnetic resonance imaging (MRI) showed regressive systemic disease but a residual mass at the right seminal vesicle. For histologic re-evaluation, 3-dimensional-controlled stereotactic MRI/transrectal ultrasound (TRUS)-fusion biopsy specimens were taken. Because histologic analysis showed nonvital tissue, a decision could be made against adjuvant radical cystoprostatectomy. Advanced 3-Tesla imaging and MRI/TRUS-fusion biopsies in children are feasible and represent an effective tool to examine suspicious pelvic lesions. Depending on histology, this can lead to a significant reduction of therapy-associated morbidity.


Davies JD, Simons CM, Ruhotina N, et al.
Anatomic basis for lymph node counts as measure of lymph node dissection extent: a cadaveric study.
Urology. 2013; 81(2):358-63 [PubMed]
OBJECTIVE: To determine the number, variability, and distribution of pelvic lymph nodes to better understand the utility of the node count as a surrogate for the dissection extent. Although pelvic lymph node dissection (PLND) at radical cystectomy for bladder cancer is critical for disease control and staging, debate regarding the measurement of dissection adequacy remains. Many have proposed minimum node counts, yet an anatomic study assessing the number and variability of lymph nodes in the PLND templates is lacking.
MATERIALS AND METHODS: Super-extended PLND was performed on 26 human cadavers, and the lymph nodes within each of 12 dissection zones were enumerated by a single pathologist. We calculated the mean, standard deviation, and range of nodal yield within each dissection region. The super-extended and standard dissection templates were compared using the paired t test.
RESULTS: Super-extended PLND yielded a mean of 28.5 ± 11.5 lymph nodes, with a total node count range of 10-53 nodes. In contrast, the nodal yield within the standard template was 18.3 ± 6.3 nodes, with a range of 8-28 nodes (P <.001). No significant differences were seen in lymph node counts when stratified by age, sex, or cause of death.
CONCLUSION: Using a cadaveric model and a single pathologist to eliminate many of the factors affecting the nodal yield in surgical series, we found substantial interindividual differences, with counts ranging from 10 to 53 nodes. These results have demonstrated the limited utility of lymph node count as a surrogate for the dissection extent and illustrated the challenges associated with implementing a surgical standard for minimum lymph node counts.


Serretta V, Altieri V, Morgia G, et al.
Cigarette smoking status at diagnosis and recurrence in intermediate-risk non-muscle-invasive bladder carcinoma.
Urology. 2013; 81(2):277-81 [PubMed]
OBJECTIVE: To study the effect of smoking status at diagnosis on recurrence in intermediate-risk non-muscle-invasive bladder carcinoma treated by transurethral resection (TUR) of the bladder and early intravesical chemotherapy.
METHODS: Tumor characteristics and smoking status were recorded in 395 patients entered in a randomized multicenter trial comparing 2 different schedules of early intravesical chemotherapy. All patients received intravesical epirubicin (80 mg/50 mL) within 6 hours after TUR, followed by 5 more weekly instillations with (arm B) or without (arm A) monthly instillations for 1 year. Smoking habit was investigated at diagnosis through a structured questionnaire. Multivariate statistical analysis was performed to study the recurrence-free survival (RFS) and the recurrence-free rate (RFR) in relation to smoking status.
RESULTS: Ninety-seven (24.6%) patients never smoked and 298 (75.4%) were smokers. At a median follow-up of 48 months, 117 patients (29.6%) recurred, 63 in arm A and 54 in arm B (P = .43). Ten patients (2.5%) progressed. The 3-year RFS, RFR, and median time to first recurrence of smokers and patients who never smoked were 64.0% and 71.3% (P = .08), 69.1% and 74.2% (P = .16), and 13.6 and 14.2 months (P = .27), respectively. The multivariate analysis identified previous history (P = .01) and smoking status (P = .04) as the main prognostic factors for recurrence in these patients. No difference in recurrence risk at 3 years was detected between current and former smokers.
CONCLUSION: In intermediate-risk non-muscle-invasive bladder carcinoma treated by early intravesical chemotherapy, smoking status influences significantly the 3-year RFS. No difference was detected between current and former smokers.


Roychowdhury A, Dey RK, Bandyapadhyay A, et al.
Study of mutated p53 protein by immunohistochemistry in urothelial neoplasm of urinary bladder.
J Indian Med Assoc. 2012; 110(6):393-6 [PubMed]
It is difficult to predict which urothelial neoplasm would subsequently recur or progress to muscle invasive tumours or produce metastasis.The aim and objective of the study were to evaluate the scope of immunohistochemical expression of p53 in human urothelial neoplasms with regard to grade, stage and outcome of the patients. Eighteen consecutive patients were taken and urothelial tumour samples were obtained from transurethral resection or surgical excision. Histopathological examinations were performed and the grading was done according to the WHO/ISUP consensus classification of urothelial neoplasms. Immunohistochemical staining for p53 was performed on formalin fixed paraffin embedded tissue sections with appropriate positive and negative control. It was found 3 patients with papillary urothelial neoplasm of low malignant potential (PUNLMP), 5 cases of papillary low grade urothelial carcinoma, 10 patients with papillary high grade urothelial carcinoma including 2 cases of invasive urothelial carcinoma. All three PUNLMP cases showed negative results. Four out of 5 low grade papillary urothelial carcinoma had nuclear p53 accumulation, while all of the 10 papillary high grade carcinoma had high p53 index. The finding of negative p53 staining in PUNLMPs and high p53 index in high grade papillary urothelial carcinomas and invasive carcinomas support the notion that mutation of p53 gene might be unrelated to the development of urothelial neoplasms but definitely play a crucial role in progression of the malignancy.


Wu S, Li F, Huang X, et al.
The association of tea consumption with bladder cancer risk: a meta-analysis.
Asia Pac J Clin Nutr. 2013; 22(1):128-37 [PubMed]
The association between tea consumption and bladder cancer has been confirmed in several animal studies, but one epidemiological study in 2001 showed no association between them. In order to provide an accurate assessment of this, we conducted a meta-analysis on tea consumption and bladder cancer risk. Studies were identified by a literature search in PubMed from January 1980 to March 2012 and the reference lists of relevant studies. Random effect models were used to calculate summary relative risk estimates (RR) and their corresponding 95% confidence intervals (CI) based on high contrast to low intake values. Twenty-four publications (6 cohort studies and 18 case-control studies) based on consumption of overall tea, black tea, and green tea to bladder cancer risk were included in this analysis. For overall tea, the summary RR indicated no association between tea consumption and bladder cancer (RR= 1.09, 95%CI: 0.85-1.40). In subgroup analyses, we found a moderate increase of bladder cancer risk in smoking group (RR= 1.77, 95%CI: 1.04-3.01). In the black tea group, no statistically significant association was observed (RR= 0.84, 95%CI: 0.70-1.01). Interestingly, in the subgroup of sex, a protective effect was observed between tea consumption and bladder cancer risk in female (RR= 0.61, 95%CI: 0.38- 0.98). For green tea group, there was no relationship associated with bladder cancer risk (RR= 1.03, 95%CI: 0.82- 1.31). In conclusion, our data suggest that high overall tea intake in smokers increased the risk of bladder cancer, and high black tea intake in female may reduce the risk of bladder cancer.


Lambert JW, Ingham M, Gibbs BB, et al.
Using preoperative albumin levels as a surrogate marker for outcomes after radical cystectomy for bladder cancer.
Urology. 2013; 81(3):587-92 [PubMed]
OBJECTIVE: To evaluate preoperative albumin levels as a marker for comparing survival outcomes after cystectomy in patients with bladder cancer.
MATERIALS AND METHODS: We performed a retrospective record review using our bladder cancer database of 238 patients from 2004 to 2011. Of these, we included 187 patients with sufficient data for analysis, aged 35 years or older, who survived to undergo cystectomy. Serum albumin levels were routinely checked the day before cystectomy. Overall survival and cancer-specific survival by albumin levels were compared using Kaplan-Meier and Cox proportional hazards regression models. Complication rates between albumin groups were compared by a 2-sample test of proportions.
RESULTS: Thirty-one patients (16.5%) were in the low-albumin cohort (defined as albumin <3.5 g/dL), and 156 patients had albumin levels within normal reference ranges. Multivariable analysis showed overall survival at 3 years was 41% and 56% (adjusted hazard ratio, 1.76; P = .04) and cancer-specific survival was 57% and 72% (hazard ratio, 1.57; P = .22) in the low- and normal-albumin groups, respectively. Overall complication rates were significantly higher in the cohort with low albumin than in those with normal albumin (87% vs 65%; P = .014).
CONCLUSION: Our single-institution retrospective study demonstrates that patients with low preoperative albumin levels had an increased overall mortality and cancer-specific mortality risk than those with normal albumin levels. Albumin may therefore be a reflection of disease state as well as nutritional status.


Vogelzang NJ
Antiangiogenic agents, chemotherapy, and the treatment of metastatic transitional cell carcinoma.
J Clin Oncol. 2013; 31(6):670-5 [PubMed]
A 69-year-old man with a 100 pack-year history of smoking developed gross hematuria. His medical history included hypertension, a silent myocardial infarction, and a cerebrovascular accident complicated by seizures. Cystoscopy and biopsy showed a 4-cm mass at the right ureteral orifice positive for a high-grade papillary transitional cell carcinoma (TCC) with muscularis propria invasion (Fig 1). The computed tomography (CT)/positron emission tomography (PET) scan of the chest, abdomen, and pelvis showed hydronephrosis and hydroureter with marked cortical thinning and multiple bilateral PET-avid pulmonary nodules, with the largest in the left upper lung measuring 3.0 × 2.5 cm (Figs 2A, 3A), biopsy of which showed invasive high-grade urothelial carcinoma. The patient consented to join a clinical trial for metastatic TCC (USON [US Oncology Network study] 06040) involving treatment with gemcitabine, cisplatin, and sunitinib (GCS) 37.5 mg per day. Four days later, he experienced a 10-day hospitalization for acute pancreatitis and neutropenia. Sunitinib was discontinued, and he completed four additional cycles of GC. CT/PET showed that the right ureteral mass and all lung nodules had regressed or disappeared (Figs 2B, 3B). The largest remaining lung nodule at 1.4 cm showed no metabolic activity. He underwent a radical cystoprostatectomy and right nephroureterectomy, disclosing residual high-grade urothelial carcinoma infiltrating the full thickness of the ureteral wall. There was carcinoma in situ of the bladder, and 42 nodes were negative for cancer. The surgery was followed by a small, uncomplicated myocardial infarction. A scheduled left thoracotomy to remove the remaining nodule was cancelled. No additional chemotherapy was administered, and the patient remains free of recurrence 2 years from initiation of chemotherapy. The 1.4-cm nodule has calcified and remains stable and metabolically inactive. He has no sequelae of chemotherapy or surgery, with a creatinine level of 1.35 mg/dL.


Omran OM
CD10 and E-cad expression in urinary bladder urothelial and squamous cell carcinoma.
J Environ Pathol Toxicol Oncol. 2012; 31(3):203-12 [PubMed]
Identification of prognostic markers in bladder carcinoma comprises a major clinical issue and therapeutic target. CD10 and the adhesion molecule E-cadherin (E-cad) are expressed in a variety of normal tissues and their neoplasms. CD10 is able to degrade extracellular matrix and other proteins, including adhesion molecules. The roles of CD10 and E-cad and their relationship in the development and progression of bladder carcinoma are poorly understood. The aim of this study was to investigate the expression of CD10 and E-cad in bladder carcinomas and relate the results to the established prognostic factors. This study included 144 patients with bladder carcinoma, including 72 with transitional cell carcinoma (TCC; 30 bilharzial and 42 nonbilharzial) and 72 with squamous cell carcinoma (SCC; 38 bilharzial and 34 nonbilharzial). Immunohistochemical analysis for both CD10 and E-cad were carried out on paraffin-fixed sections of neoplastic bladder tissues. CD10 tumor cells, CD10 stromal cells, and E-cad were expressed in 56%, 58%, and 51% of cancer bladder cases, respectively. There was a statistically significant correlation between percentage of tumor cells positively stained by CD10 and each of the tumor grade, clinical stage, and lymph node metastasis of both TCC and SCC. There was a significant statistical correlation between immunostaining by E-cad marker and each of the tumor grade, clinical stage, and lymph node metastasis of TCC, but no such association with SCC. The frequency of stromal expression of CD10 was higher in bilharzial-associated bladder carcinomas than in nonbilharzial ones, and these results were statistically significant. In conclusion, increased expression of CD10 in the tumor and stromal cells of both TCC and SCC and decreased expression of E-cad in the tumor cells of only TCC are strongly correlated with tumor progression, invasion, and metastasis in human bladder cancer.


Liu D, Zhang Z, Kong CZ
High FOXM1 expression was associated with bladder carcinogenesis.
Tumour Biol. 2013; 34(2):1131-8 [PubMed]
The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including bladder cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in bladder cancer remain unclear. Real-time quantitative PCR, Western blot and immunohistochemistry were used to explore FoxM1 expression in bladder cancer cell lines, primary bladder cancer clinical specimens and normal bladder tissues. FoxM1 expression was knocked down by small interfering RNA (siRNA) in T24 cells; proliferation, migration and invasion were assayed. FoxM1 expression was up-regulated in the majority of the bladder cancer tissue specimens at both mRNA and protein levels. Immunohistochemistry analysis showed that FoxM1 expression was significantly correlated with TNM stage and histological grade, metastasis. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation, migration and invasion. These results suggested that FOXM1 up-regulation was associated with poor prognosis in bladder cancer, and therefore it might act as a prognostic marker and a new potential target for bladder cancer treatment.


Mitra AP, Castelao JE, Hawes D, et al.
Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program.
Cancer. 2013; 119(4):756-65 [PubMed] Article available free on PMC after 15/02/2014
BACKGROUND: Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort.
METHODS: Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking.
RESULTS: Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively).
CONCLUSIONS: Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.


Muto S, Nakajima A, Horiuchi A, et al.
Maintenance therapy with intravesical bacillus Calmette-Guerin in patients with intermediate- or high-risk non-muscle-invasive bladder cancer.
Jpn J Clin Oncol. 2013; 43(3):305-13 [PubMed]
OBJECTIVE: We investigated the efficacy, safety and an optimal schedule of maintenance therapy with intravesical instillation of Bacillus-Calmette Guérin in patients with non-muscle-invasive bladder cancer.
METHODS: We compared the oncological outcome and adverse events of maintenance Bacillus-Calmette Guérin therapy (n = 40) with control subjects (n = 64) of Bacillus-Calmette Guérin induction therapy. Maintenance therapy was scheduled to be administered in 3-week cycles at 6, 12, 18, 24 and 36 months after the induction therapy.
RESULTS: There was a significant difference in the 5-year recurrence-free survival rate between the maintenance and induction groups in all patients (72.4 vs. 62.0%; P = 0.019) and in patients with high recurrence risk (100.0 vs. 17.9%; P = 0.009). There was a significant difference in the 5-year progression-free survival rate between the maintenance and induction groups in patients with high progression risk (100.0 vs. 69.3%; P = 0.047). Maintenance Bacillus-Calmette Guérin instillations for a total of four times or more (recurrence-free survival: hazard ratio: 0.2, P = 0.039) or with a total dosage of >243 mg (recurrence-free survival: hazard ratio: 0.2, P = 0.041) after 6 months of induction therapy significantly improve tumor recurrence-free survival and progression-free survival. There were no significant differences between induction therapy and maintenance therapy in the frequency of all adverse drug reactions.
CONCLUSIONS: Bacillus-Calmette Guérin maintenance therapy was effective in preventing the recurrence and progression of high-risk non-muscle-invasive bladder cancer. Maintenance Bacillus-Calmette Guérin instillations for a total of four times or more or with a total dosage of >243 mg after 6 months of induction therapy are necessary to obtain the optimal effect as maintenance therapy.


Wagener N, Bulkescher J, Macher-Goeppinger S, et al.
Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients.
Br J Cancer. 2013; 108(4):973-82 [PubMed] Article available free on PMC after 05/03/2014
BACKGROUND: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer.
METHODS: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry.
RESULTS: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients.
CONCLUSION: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.


Miyachika Y, Yamamoto Y, Matsumoto H, et al.
Centrosome amplification in bladder washing cytology specimens is a useful prognostic biomarker for non-muscle invasive bladder cancer.
Cancer Genet. 2013 Jan-Feb; 206(1-2):12-8 [PubMed]
We investigated whether centrosome amplification (CA) obtained from bladder washing cytology (BWC) specimens may be a useful prognostic biomarker for patients with non-muscle invasive bladder cancer (NMIBC). The study cohort included 78 patients with pathologically confirmed NMIBC. BWC specimens were obtained from all patients during transurethral resection of bladder tumor (TURBT), and CA was evaluated by immunofluorescence staining using a pericentrin polyclonal antibody. A positive case of CA was defined as a specimen in which >5% of cells contained ≥3 centrosomes per cell. CA was detected in 26.9% (21 of 78) of BWC specimens obtained from NMIBC patients. Disease progression was observed in 11.5% (9 of 78) of patients, with a median follow-up of 32 months. In univariate analyses, CA obtained from BWC specimens, initial or recurrent, and washing cytology were significantly associated with progression-free survival (P = 0.009, 0.02, and 0.03, respectively). Multivariate Cox model analyses revealed that CA was the most significant prognostic factor for disease progression (hazard ratio: 2.22, 95% confidence interval: 1.13-4.90, P = 0.022). These data suggest that analysis of CA using bladder washing cytological specimens may provide crucial predictive information regarding disease progression in NMIBC.


Yin L, Bu H, Chen M, et al.
Perivascular epithelioid cell neoplasm of the urinary bladder in an adolescent: a case report and review of the literature.
Diagn Pathol. 2012; 7:183 [PubMed] Article available free on PMC after 05/03/2014
Perivascular epithelioid cell neoplasms (PEComas) of the urinary bladder are extremely rare and the published cases were comprised predominantly of middle-aged patients. Herein, the authors present the first urinary bladder PEComa occurring in an adolescent. This 16-year-old Chinese girl present with a 3-year history of abdominal discomfort and a solid mass was documented in the urinary bladder by ultrasonography. Two years later, at the age of 18, the patient underwent transurethral resection of the bladder tumor. Microscopically, the tumor was composed of spindled cells mixed with epithelioid cells. Immunohistochemically, the tumor were strongly positive for HMB45, smooth muscle actin, muscle-specific actin, and H-caldesmon. Fluorescence in situ hybridization analysis revealed no evidence of EWSR1 gene rearrangement. The patient had been in a good status without evidence of recurrence 13 months after surgery. Urinary bladder PEComa is an extremely rare neoplasm and seems occur predominantly in middle-aged patients. However, this peculiar lesion can develop in pediatric population and therefore it should be rigorously distinguished from their mimickers. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1870004378817301.


Iwasaki K, Obara W, Kato Y, et al.
Neoadjuvant gemcitabine plus carboplatin for locally advanced bladder cancer.
Jpn J Clin Oncol. 2013; 43(2):193-9 [PubMed]
OBJECTIVE: Although cisplatin-based neoadjuvant chemotherapy followed by cystectomy was demonstrated to improve the survival among patients with locally advanced bladder cancer, its severe adverse events, including nephrotoxicity, are critical issues. We investigated the safety and activity of carboplatin, a mild nephrotoxic agent, combined with gemcitabine as a neoadjuvant chemotherapy compared with methotrexate, vinblastine, doxorubicin and cisplatin for patients with locally advanced bladder cancer.
METHODS: We retrospectively evaluated 68 patients with locally advanced bladder cancer who received neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (n = 34) or gemcitabine and carboplatin (n = 34) followed by cystectomy at our institute. The adverse events, chemotherapy delivery profile, rate of down-stage and recurrence-free survival were assessed for methotrexate, vinblastine, doxorubicin and cisplatin compared with gemcitabine and carboplatin.
RESULTS: The mean cycles of methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and carboplatin, were 2.5 and 2.7, respectively. The hematologic adverse events of Grade 3 or 4 neutropenia, anemia and thrombocytopenia for methotrexate, vinblastine, doxorubicin and cisplatin were 15, 18 and 0%, respectively. The occurrences for gemcitabine and carboplatin were 53, 21 and 50%, respectively. Grade 3 or 4 non-hematologic toxicities for methotrexate, vinblastine, doxorubicin and cisplatin were nausea and vomiting in 24%, and were not observed for gemcitabine and carboplatin. The lowest median estimated glomerular filtration rate during methotrexate, vinblastine, doxorubicin, and cisplatin and gemcitabine and carboplatin was 55.8 and 70.6 ml/min/1.73 m(2), respectively (P = 0.002). The rate of down-stage to pT1 or less was 59% for methotrexate, vinblastine, doxorubicin and cisplatin, and 53% for gemcitabine and carboplatin (P = 0.624). The recurrence-free survival of methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and carboplatin, at 36 months from the diagnosis was 79 and 75%, respectively (P = 0.85).
CONCLUSIONS: Neoadjuvant gemcitabine and carboplatin showed less non-hematologic toxicity than methotrexate, vinblastine, doxorubicin and cisplatin, and especially less nephrotoxicity was demonstrated for gemcitabine and carboplatin. Although observed during the short term, the recurrence-free survival for gemcitabine and carboplatin was comparable to that for methotrexate, vinblastine, doxorubicin and cisplatin.


Johnson DT, Luong R, Lee SH, et al.
Deletion of leucine zipper tumor suppressor 2 (Lzts2) increases susceptibility to tumor development.
J Biol Chem. 2013; 288(6):3727-38 [PubMed] Article available free on PMC after 08/02/2014
Using an Lzts2 knock-out mouse model, we characterized the biological role of Lzts2 in tumorigenesis. Both heterozygous and homozygous deletion of the Lzts2-targeted allele in mice shows an increased incidence in spontaneous tumor development, although Lzts2 homozygous knock-out mice show significantly higher incidences than heterozygous mice. Treatment of Lzts2-deficient mice with a carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine, increases the susceptibility to N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder carcinoma development. Examination of human prostate cancer tissue specimens shows a reduction of LZTS2 protein expression in prostate cancer cells. Further analyses of mouse embryonic fibroblasts isolated from Lzts2 knock-out embryos show that loss of Lzts2 enhances cell growth. These data provide the first line of evidence demonstrating that deletion of Lzts2 increases susceptibility to spontaneous and carcinogen-induced tumor development.


Chaux A, Compérat E, Varinot J, et al.
High levels of phosphatase and tensin homolog expression are associated with tumor progression, tumor recurrence, and systemic metastases in pT1 urothelial carcinoma of the bladder: a tissue microarray study of 156 patients treated by transurethral resection.
Urology. 2013; 81(1):116-22 [PubMed]
OBJECTIVE: To evaluate immunohistochemical expression of phosphatase and tensin homolog (PTEN) and mammalian target of rapamycin (mTOR) pathway members in pT1 urothelial carcinomas treated by transurethral resection and to determine if immunohistochemistry can be used to predict prognosis.
METHODS: Formalin-fixed, paraffin-embedded tissue samples from 156 patients with pT1 urothelial carcinoma treated by transurethral resection were used to build 5 tissue microarrays. Tissue microarray sections were stained for PTEN, phosphorylated (phos)-AKT, phos-mTOR, phos-S6, eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), and phos-4EBP1. Patients were monitored after initial treatment (mean, 22.5; median, 16; range, 3-108 months) to detect tumor recurrence, tumor progression, or systemic metastases.
RESULTS: During follow-up, 101 patients (65%) showed tumor recurrence, 57 showed tumor progression (37%), and 18 showed systemic metastases (12%). Patients with ≥2 lesions at the initial workup had higher proportions and higher hazard ratios of tumor recurrence, tumor progression, and systemic metastases. Complete loss of PTEN expression was observed in 6 patients (4%), and >80% of the mTOR pathway members showed at least focal positivity. Proportions of tumors with higher levels of PTEN immunohistochemical expression were higher in patients with tumor recurrence (P=.001), tumor progression (P=.05), and systemic metastases (P=.001). Proportions of tumors with lower phos-S6 and low phos-4EBP1 levels were higher in patients with tumor recurrence (P≤.05). Proportions were similar for the remaining biomarkers.
CONCLUSION: Higher levels of PTEN immunohistochemical expression were associated with higher rates of tumor recurrence, tumor progression, and systemic metastases in patients with pT1 urothelial carcinomas treated by transurethral resection.


Lee SJ, Cho SC, Lee EJ, et al.
Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-κB) activation by inducing the up-regulation of p21(WAF1) protein expression.
J Biol Chem. 2013; 288(8):5539-52 [PubMed] Article available free on PMC after 22/02/2014
The role of inflammatory cytokine interleukin-20 (IL-20) has not yet been studied in cancer biology. Here, we demonstrated up-regulation of both IL-20 and IL-20R1 in muscle-invasive bladder cancer patients. The expressions of IL-20 and IL-20R1 were observed in bladder cancer 5637 and T-24 cells. We found that IL-20 significantly increased the expression of matrix metalloproteinase (MMP)-9 via binding activity of NF-κB and AP-1 in bladder cancer cells and stimulated the activation of ERK1/2, JNK, p38 MAPK, and JAK-STAT signaling. Among the pathways examined, only ERK1/2 inhibitor U0126 significantly inhibited IL-20-induced migration and invasion. Moreover, siRNA knockdown of IL-20R1 suppressed migration, invasion, ERK1/2 activation, and NF-κB-mediated MMP-9 expression induced by IL-20. Unexpectedly, the cell cycle inhibitor p21(WAF1) was induced by IL-20 treatment without altering cell cycle progression. Blockade of p21(WAF1) function by siRNA reversed migration, invasion, activation of ERK signaling, MMP-9 expression, and activation of NF-κB in IL-20-treated cells. In addition, IL-20 induced the activation of IκB kinase, the degradation and phosphorylation of IκBα, and NF-κB p65 nuclear translocation, which was regulated by ERK1/2. IL-20 stimulated the recruitment of p65 to the MMP-9 promoter region. Finally, the IL-20-induced migration and invasion of cells was confirmed by IL-20 gene transfection and by addition of anti-IL-20 antibody. This is the first report that p21(WAF1) is involved in ERK1/2-mediated MMP-9 expression via increased binding activity of NF-κB, which resulted in the induction of migration in IL-20/IL-20R1 dyad-induced bladder cancer cells. These unexpected results might provide a critical new target for the treatment of bladder cancer.


Zhang Y, Wang X, Zhang W, Gong S
An association between XPC Lys939Gln polymorphism and the risk of bladder cancer: a meta-analysis.
Tumour Biol. 2013; 34(2):973-82 [PubMed]
The polymorphism Lys939Gln in xeroderma pigmentosum complementation group C (XPC) gene has been reported to be associated with bladder cancer in some studies, though the results remain inconclusive. To explore this relationship between XPC Lys939Gln polymorphism and the susceptibility for bladder cancer and the impact of smoking exposures, a cumulative meta-analysis was performed in this study. PubMed and EMBASE databases have been systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between XPC Lys939Gln polymorphism and susceptibility to bladder cancer (BC). Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated. Thirteen studies were chosen in this meta-analysis, involving 4,927 BC cases (1,119 Asian, 2,670 Caucasian, and 1,138 mixed) and 5,185 controls (1,399 Asian, 2,629 Caucasian, and 1,157 mixed). The XPC 939Gln allele was significantly associated with increased risk of BC based on allelic contrast (OR = 1.11, 95 % CI = 1.02-1.21), homozygote comparison (OR = 1.35, 95 % CI = 1.08-1.68), and a recessive genetic model (OR = 1.36, 95 % CI = 1.09-1.68). The results from the present meta-analysis indicated that the 939Gln polymorphism in XPC is a risk factor for bladder carcinogenesis. Further large and well-designed studies are needed to confirm this conclusion.


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