Risk Of Urothelial Carcinoma Research Articles

Environmental Exposures and Canine Bladder Cancer: A Case Control Study Using Silicone Passive Samplers.

Pet dogs offer valuable models for studying environmental impacts on human health due to shared environments and a shorter latency period for cancer development. We assessed environmental chemical exposures in a case-control study involving dogs at high risk of urothelial carcinoma, identified by a BRAF V595E mutation in urinary epithelial cells. Cases (n = 25) exhibited low-level BRAF mutations, while controls (n = 76) were matched dogs without the mutation. Each dog wore a silicone sampler for five continuous days to assess environmental exposures. Silicone samplers were analyzed using targeted and suspect screening (i.e., nontargeted) methods. Of 115 targeted chemicals, 39 were detected in >50% of samplers, with cases showing significantly higher levels (2-3×) of BDE-47, BDE-99, anthracene, and benzyl butyl phthalate (p < 0.05). Suspect screening identified that cases were exposed to more chemicals, often at higher exposure levels. For example, cases had significantly higher levels of 25 chemical features compared to controls (p < 0.05). This is the largest study to date to quantify such a wide breadth of contaminant exposure levels associated with canine urothelial carcinoma and the first to assess a population with subclinical disease, highlighting pet dogs as models to study environmental contributions to cancer risk, advancing both human and veterinary health.

Statin therapy and upper tract urothelial carcinoma risk in hyperlipidemic patients with chronic kidney disease and end-stage kidney disease, a population-based 17-year follow-up study

Background The upper tract urothelial carcinoma (UTUC) risk associated with statin therapy in hyperlipidemic patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) remains obscure. Aim This retrospective cohort study investigated the UTUC risk for hyperlipidemic patients with CKD or ESKD associated with statin therapy. Methods From the national insurance claims data of Taiwan, we identified hyperlipidemic patients and established three pairs of statin users and non-users sub-cohorts matched by propensity scores: 401,490 pairs with normal kidney function, 37,734 pairs with CKD, and 6271 pairs with ESKD. Incidence rates and hazard ratio (HR) of UTUC were estimated, by the end of 2016, between statin and non-statin cohorts, and between hydrophilic statins users and lipophilic statins users. Time-dependent model estimated adjusted HR, and sub-distribution HR (sHR) accounting for the competing risk of deaths. Results The statin-users with ESKD were at increased UTUC risk (sHR 1.98; 95% confidence interval (CI), 1.28–3.06), significant for younger patients (40–64 years). The incidence was twofold greater in women than in men (31.8 versus 15.9 per 10,000 person-years). Receiving lipophilic statins was associated with increased UTUC risk in CKD and ESKD patients, while receiving hydrophilic statins was associated with increased UTUC risk in ESKD patients. Conclusions Patients with ESKD receiving statin were at an increased UTUC risk, significant for younger group (<65 y/o). The positive associations between UTUC and statin persisted in both genders with ESKD, and in therapy with either lipophilic statins or hydrophilic statins. Statin users with ESKD deserve attention for UTUC prevention.

Risk of Metachronous Upper Tract Urothelial Carcinoma After Ureteral Stenting in Patients With Bladder Cancer

ObjectiveSparse data exist on the impact of upper urinary tract (UUT) decompression on the risk of UUT recurrence in patients with bladder cancer (BCa). This study aims to evaluate whether Double J stenting (DJS) can increase the risk of UUT recurrence compared to percutaneous nephrostomy (PCN) placement. Materials and methodsWe retrospectively analyzed data from 1550 patients with cTa-T3NanyM0 BCa who underwent radical cystectomy (RC) between at 12 tertiary care centers (1990-2020). Patients with complete follow-up, no prior history of UUT cancer, and who required UUT decompression for preoperative hydronephrosis were selected. Hydronephrosis grade was defined according to established scoring systems. UUT recurrence was diagnosed through imaging, urinary cytology, and confirmed by selective cytology and ureteroscopy when possible. Propensity scores were computed to determine overlap weights and balance groups. Kaplan–Meier analyses estimated UUT recurrence-free survival (RFS), cancer-specific (CSS), and overall survival (OS) before and after weighting. Cox regression analyses before and after weighting were fitted to predict UUT recurrence. ResultsOf 524 included patients, 132 (25%) and 392 (75%) patients were managed with DJS and PCN placement, respectively. Patients who received PCN had higher grade (≥ 3) of obstruction (34% vs. 14%) and pT3-4 tumors (70% vs. 36%) than patients with DJS. During a median follow-up of 19 months, 2-years UUT-RFS did not differ between groups (95% for PCN vs 92% for DJS, weighted HR 1.41, 95% CI, 0.55-3.59). There was no difference in 2-years weighted CSS (74% vs. 74%) and OS (67% vs 69%). Main limitations were the short follow-up and inclusion of patients uniquely undergoing RC. ConclusionsThese results suggest that ureteral DJS does not increase the risk of developing UUT recurrence in BCa patients with hydronephrosis requiring UUT decompression. However, UUT recurrence was rare, and associations were weak, with findings susceptible to bias. Randomized trials are needed to validate these results.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

The impact of double-J ureteral stenting before radical cystectomy on the development of upper tract urothelial carcinoma.

It is controversial whether the use of a double-J stent (DJ) in patients with bladder cancer before radical cystectomy (RC) increases the risk of tumour seeding in the upper tract and thus the risk of metachronous upper tract urothelial carcinoma (UTUC). The aim of our study is to investigate the risk of upper tract recurrence after RC in patients previously managed with a DJ stent. A total of 699 patients who had undergone RC between January 2003 and March 2022 with complete perioperative data and pathological outcome were included in our study. Patients treated preoperatively with a DJ stent were identified and compared for development of metachronous UTUC with those who did not receive prior internal stenting. Multivariable Cox regression analysis was used to determine predictors of UTUC occurrence among the possible pathological features; risk factors for mortality after RC were also examined. Of 699 patients, 117 (16.7%) were managed preoperatively with a DJ stent. The overall probability of metachronous UTUC was 1%, 4% and 6% at 1, 3 and 5 years, respectively. The groups with and without DJ stenting were comparable regarding their clinicopathologic features, except for the higher incidence of hydronephrosis in the DJ group. At similar follow-up periods (median follow-up 32 months), metachronous UTUC was detected in four (3.4%) patients in the DJ group and in 13 (2.2%) in the non-stented group (P=0.44). The median interval (IQR) from cystectomy to UTUC was 40.5 (20-49) months in the DJ group and 37 (24-82) in the non-stented group (P=0.7). In the multivariable analysis, only presence of CIS (HR 3.83, 95% CI 1.19-12.29, P=0.024) and positive ureteral margin (HR=5.2, 95% CI 1.38-19.57, P=0.015) were predictors of metachronous UTUC. The study is limited by the retrospective nature and relatively short follow-up. Ureteral stenting for management of hydronephrosis in patients with bladder cancer undergoing RC is a viable option, without higher risk for UTUC or mortality. Patients with positive ureteral margin and CIS are considered high-risk groups for upper tract recurrence and should receive long-term, rigorous follow-up.

53 The Diagnostic Performance of Uromonitor in the Evaluation of Patients at Risk for Urothelial Carcinoma

53 The Diagnostic Performance of Uromonitor in the Evaluation of Patients at Risk for Urothelial Carcinoma

La version 2022 du Système de Paris : quoi de neuf ?

The second version of the Paris System for reporting urine cytology was published in 2022. It follows the first version in 2016, which was very successful and widely adopted by many cytopathologists from different countries. Thus, numerous publications using the Paris system have made it possible to refine the criteria as well as discussing the limits. The diagnosis accuracy of urinary cytology is high for detection of high grade urothelial carcinoma, but not for low-grade where there are few cytological abnormalities. So, the chapter individualizing low-grade urothelial neoplasms was deleted, the latter were included in the category “negative for high-grade urothelial carcinoma‿. Indeed, the risk of malignancy is replaced by the risk of high-grade urothelial carcinoma. A new chapter has been devoted to urothelial tumors of the upper tract. Finally, the pitfalls linked to cellular degeneration are discussed for each category. The risk of high-grade malignancy associated with each category, will help communication with the clinician and patient care.

Transporter Associated With Antigen Processing (TAP) 1 Gene Polymorphisms and Risks of Urothelial Cell Carcinoma Among the Japanese Population.

Urothelial cell carcinoma is one of the costliest types of cancer because of its recurrence, lengthy course of therapy, and tendency to lead to further complications. Gene polymorphisms are one of many factors that are thought to cause the carcinogenesis of urothelial cell carcinoma. Two single-nucleotide polymorphisms (SNPs) of the transporter associated with antigen processing (TAP) 1 gene and their relationship with the risks of urothelial cell carcinoma in the Japanese population were examined in this study by using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) for genotyping and statistical analysis. The adjusted odd ratios with 95% confidence interval (CI) of the mutant types (A/G+G/G) in females for the I333V and D637G polymorphisms are 2.28 (1.11-4.66) and 2.50 (1.21-5.17), respectively. The findings showed that females with the (A/G+G/G) genotype are more likely to develop urothelial cell carcinoma than those with the A/A genotype. Any correlation between smoking and gene polymorphism was absent. Results indicate that TAP1 gene polymorphisms and the risk of urothelial cell carcinoma are related in females.

A Model Based on Automated Urinalysis Parameters for Urothelial Carcinoma Risk Stratification in Suspected Patients.

The aim of this study was to develop and validate a risk stratification model for the screening of patients with suspected urothelial carcinoma (UC). We enrolled 671 consecutive patients with suspected UC and generated a risk stratification model based on urinary parameters by using an automated urinalysis analyzer (Sysmex UN-9000). All patients received urine cytology examination from January 1, 2019, to October 31, 2022. Out of the 671 patients, 191 (28.5%) were ultimately diagnosed with UC. The four features associated with the presence of malignancy on multivariable analysis can be summarized by using the mnemonic UC-PAAS: UC, protein vs. creatinine ratio (P/C), age, atypical cells (Atyp.C), and small round epithelial cell (SRC). Major criteria include Atyp.C ≥ 0.1/μL (2 points) and age ≥ 65 years (2 points); minor criteria include SRC ≥ 2.7/μL (1 point) and abnormal P/C results (1 point). The model evidenced good discrimination (area under the curve = 0.802, 95% confidence interval [0.756, 0.848]) in the training group. A UC-PAAS cutoff of more than 4 points identified a high-risk population, of whom 37 of 59 (62.7%) had UC; the negative predictive value was 0.867. The validation group yielded similar findings. We present a urinalysis-based screening model, the UC-PAAS, that may serve as an accessory clinical tool for the evaluation of patients with suspected UC, because the model identifies patients at higher risk who require closer follow-up than others or additional examinations.

Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study

Canine urothelial carcinoma (UC) initially responds favorably to treatment, but is ultimately lethal in most cases. Research to identify modifiable risk factors to prevent the cancer is essential. The high breed-associated risk for UC, e.g. 20-fold higher in Scottish terriers, can facilitate this research. The objective was to identify environmental and host factors associated with UC in a cohort of Scottish terriers. Information was obtained through dog owner questionnaires for 120 Scottish terriers ≥ 6 years old participating in a bladder cancer screening study, with comparisons made between dogs that did or did not develop UC during the 3 years of screening. Univariable models were constructed, and variables with P < 0.20 were included when building the multivariable model, and then removed using a backward stepwise procedure. P < 0.05 was considered statistically significant. Urine cotinine concentrations were measured by liquid chromatography-mass spectrometry to further investigate potential cigarette smoke exposure. Biopsy-confirmed UC which was found in 32 of 120 dogs, was significantly associated with the dogs living in a household with cigarette smokers (odds ratio [OR], 6.34; 95 % confidence intervals [CI], 1.16–34.69; P = 0.033), living within a mile of a marsh or wetland (OR, 21.23; 95 % CI, 3.64–123.69; P = 0.001), and history of previous bladder infections (OR, 3.87; 95 % CI, 1.0–14.98; P = 0.050). UC was diagnosed in 18 of 51 dogs (35.3 %) with quantifiable cotinine concentrations, and six of 40 dogs (15.0 %) without quantifiable cotinine concentrations in their urine (P = 0.0165). In conclusion, the main modifiable risk factor for UC in this cohort of dogs was exposure to second-hand tobacco smoke.

Upper Tract Urothelial Carcinoma (UTUC) Diagnosis and Risk Stratification: A Comprehensive Review.

Diagnosis and risk stratification are cornerstones of therapeutic decisions in the management of patients with upper tract urothelial carcinoma (UTUC). Diagnostic modalities provide data that can be integrated, to provide nomograms and stratification tools to predict survival and adverse outcomes. This study reviews cytology, ureterorenoscopy and the novel tools and techniques used with it (including photodynamic diagnosis, narrow-band imaging, optical coherence tomography, and confocal laser endomicroscopy), and biopsy. Imaging modalities and novel biomarkers are discussed in another article. Patient- and tumor-related prognostic factors, their association with survival indices, and their roles in different scores and predictive tools are discussed. Patient-related factors include age, sex, ethnicity, tobacco consumption, surgical delay, sarcopenia, nutritional status, and several blood-based markers. Tumor-related prognosticators comprise stage, grade, presentation, location, multifocality, size, lymphovascular invasion, surgical margins, lymph node status, mutational landscape, architecture, histologic variants, and tumor-stroma ratio. The accuracy and validation of pre-operative predictive tools, which incorporate various prognosticators to predict the risk of muscle-invasive or non-organ confined disease, and help to decide on the surgery type (radical nephroureterectomy, or kidney-sparing procedures) are also investigated. Post-operative nomograms, which help decide on adjuvant chemotherapy and plan follow-up are explored. Finally, a revision of the current stratification of UTUC patients is endorsed.

Reliability of the IDENTIFY calculator in stratifying risk of urothelial carcinoma in patients with haematuria: An initial evaluation at an Australian centre.

Reliability of the IDENTIFY calculator in stratifying risk of urothelial carcinoma in patients with haematuria: An initial evaluation at an Australian centre.

GPX3 rs8177412 Polymorphism Modifies Risk of Upper Urothelial Tumors in Patients with Balkan Endemic Nephropathy.

Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16-9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27-11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75-3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma.

ThePSMB8andPSMB9immunoproteasomegenes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) inPSMB9andPSMB8. We determined any associations between these SNPs and susceptibility to UBC in the Saudi community. Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for thePSMB9rs17587 G>A andPSMB8rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model. ThePSMB9rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21,P< 0.0001). In contrast, thePSMB8rs2071543 SNP showed no association with UBC risk (OR = 1.13,P= 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1;P= 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4;P= 0.0026) models. Genotypic distribution of thePSMB8rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (P> 0.05). These results suggest a potential role forPSMB9as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.

PRR11 is a prognostic biomarker and correlates with immune infiltrates in bladder urothelial carcinoma

Abnormal proline-rich protein 11 (PRR11) expression is associated with various tumors. However, there are few reports concerning PRR11 with prognostic risk, immune infiltration, or immunotherapy of bladder urothelial carcinoma (BLCA). This study is based on online databases, such as Oncomine, GEPIA, HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB, and BLCA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, we employed an array of bioinformatics methods to explore the potential oncogenic roles of PRR11, including analyzing the relationship between PRR11 and prognosis, tumor mutational burden (TMB), microsatellite instability, and immune cell infiltration in BLCA. The results depict that PRR11 is highly expressed in BLCA, and BLCA patients with higher PRR11 expression have worse outcomes. In addition, there was a significant correlation between PRR11 expression and TMB and tumor immune infiltration. These findings suggest that PRR11 can be used as a potential marker for BLCA patient assessment and risk stratification to improve clinical prognosis, and its potential regulatory mechanism in the BLCA tumor microenvironment and targeted therapy is worthy of further investigation.

Relative Risk of Bladder and Kidney Cancer in Lynch Syndrome: Systematic Review and Meta-Analysis.

Background: The association between Lynch syndrome (LS) and a higher risk of upper tract urothelial carcinoma is well established, but its effect on the risk of bladder and kidney cancers remains controversial. This review aimed to compare the relative risk (RR) of bladder and kidney cancer in confirmed LS germline mutation carriers compared to the general population. Methods: Medline, Embase, Cochrane Central, and Google Scholar were searched on 14 July 2022 for studies published in English that reported on the rates of urological cancer in adults with confirmed LS germline mutation. The quality of included studies was assessed using Cochrane’s tool to evaluate risk of bias in cohort studies. Random effects meta-analysis estimated the pooled relative risk of bladder and kidney cancer in LS carriers compared to the general population. The quality of the overall evidence was evaluated using GRADE. Results: Of the 1839 records identified, 5 studies involving 7120 participants from 3 continents were included. Overall, LS carriers had a statistically significantly higher RR of developing bladder cancer (RR: 7.48, 95% CI: 3.70, 15.13) and kidney cancer (RR: 3.97, 95% CI: 1.23, 12.81) compared to unaffected participants (p < 0.01). The quality of the evidence was assessed as “low” due to the inclusion of cohort studies, the substantial heterogeneity, and moderate-to-high risk of bias. Conclusion: Lynch syndrome is associated with a significant increase in the relative risk of kidney and bladder cancer. Clinicians should adopt a lower threshold for germline mutation genetic testing in individuals who present with bladder cancer. Further studies evaluating the role and cost-effectiveness of novel urine-based laboratory tests are needed. High-quality studies in histologically proven renal cell carcinoma and their underlying germline mutations are necessary to strengthen the association with LS.

Clinicopathological characteristics and outcomes of synchronous renal cell carcinoma and urothelial carcinoma: A population-based analysis.

To better understand the characteristics, and survival outcomes of synchronous renal cell carcinoma (RCC) and urothelial carcinoma (UC), we described and analyzed the clinical features, factors, and prognosis of patients with synchronous RCC and UC using a large population-based database. Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified patient with concurrent RCC and UC at initial diagnosis. Their clinicopathological features and prognosis were evaluated. A logistic regression model was used to examine risk factors for the occurrence of concomitant RCC and UC, and Kaplan-Meier survival curves were used to estimate overall survival. A total of 61,454 RCC patients were identified from the SEER database, 704 (1.1%) patients presented with synchronous RCC and UC. Among these patients, concurrent bladder tumors (566/704) are more common. Subsequently, subgroup analysis based on the location of UC indicated that patients with concurrent RCC and upper tract urothelial carcinoma (UTUC) had unfavorable UC characteristics (higher tumor stage and grade), compared with patients with concomitant bladder cancer. An increased risk of concurrent UC was observed among older age, male sex, and white race. Meanwhile, papillary RCC histology [odds ratio (OR) 3.23; 95% confidence interval (CI) 2.13-4.90], and smaller tumor (OR 6.63; 95% CI 4.46-9.87) were independent risk factors for concomitant UTUC. In addition, we found that synchronous RCC and UTUC was associated with worse survival by using Kaplan-Meier and multivariable analysis [hazard ratio (HR) 2.36, 95% CI 1.89-2.95]. However, concomitant bladder cancer did not affect survival outcomes of patients with RCC (HR 1.00, 95% CI 0.86-1.17). We found that synchronous concurrent RCC and UC is relatively uncommon and mostly located in the bladder. Older age, male sex, and white race increase the risk of synchronous RCC and UC. Meanwhile, patients with papillary RCC histology, and smaller tumors are more likely to have concomitant RCC and UTUC. Furthermore, our findings suggest that synchronous RCC and UTUC has a worse prognosis, while, concomitant bladder tumor did not affect the oncological outcomes of RCC.

Interaction between blood pressure and genetic risk score for bladder cancer, and risk of urothelial carcinoma in men

There is substantial genetic predisposition to bladder cancer (BC). Recently, blood pressure (BP) was positively associated with BC risk in men, but the potential interaction with genetic susceptibility for BC is unknown. We investigated a weighted genetic risk score (wGRS) of 18 BC genetic variants, BP, and their interaction, in relation to incident urothelial cancer (UC, n = 385) risk in 10,576 men. We used Cox regression, the likelihood ratio test, and the relative excess risk for interaction to calculate hazard ratios (HR) of UC, multiplicative interaction and additive interaction respectively. There was evidence of a positive additive interaction between SBP and the wGRS in relation to aggressive (P = 0.02) but not non-aggressive (P = 0.60) UC. The HR of aggressive UC was for SBP ≥ 140 mmHg and the upper 50% of the wGRS combined 1.72 (95% CI 1.03–2.87) compared to the counterpart group. Additionally, the 20-year risk of aggressive UC in 60 year-old men was 0.78% in the low SBP/low wGRS group and 1.33% in the high SBP/high wGRS group. Our findings support a potential additive interaction between the wGRS and SBP on aggressive UC among men. If replicated, the findings on interaction may provide biological and public health insight to prevent aggressive UC.

BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

BackgroundBladder cancer is a challenging public health concern in South of Iran because of its high prevalence and the related medical expenses. Although the exact etiology of bladder cancer remains unknown, given the cell transforming ability and oncogenic potential of the members of Polyomaviridae families, this study was conducted to evaluate the magnitude of BK polyomavirus (BKPyV) and John Cunningham polyomavirus (JCPyV) among patients with bladder cancer residents in the northern shores of the Persian Gulf, South of Iran.MethodsTotally 211 patients with bladder cancer were enrolled in this study. Bladder biopsy samples of these patients and patients with interstitial cystitis as well as autoptic samples of healthy bladder were tested for detection of BKPyV and JCPyV by semi-nested PCR–RFLP followed by sequencing.ResultsBKPyV and JCPyV were detected in 1.7% and 6.1% of bladder cancer samples, respectively. These samples were infected with JCPyV genotypes 2, 3 and 6 and BKPyV genotypes I and IV. BKPyV and JCPyV coinfection was detected in 2 samples. Moreover, one of the healthy bladder samples was positive for BKPyV, and one of the interstitial cystitis samples was positive for JCPyV. Although the majority of infected patients were in the age group 70–79 years, male, residents in Tangestan, stage Ta–T1, and low-grade and high-grade papillary urothelial carcinoma, the prevalence of BKPyV and JCPyV among patients with bladder cancer was not statistically associated with age, gender, place of residency, and stage and grade of the tumor.ConclusionDespite identifying BKPyV and JCPyV in a number of bladder cancer biopsy specimens and the high prevalence of bladder cancer among people resident in South of Iran, it is suggested that these viruses are unlikely to be effective causative factors in bladder carcinogenesis in this region. Therefore, environmental risk factors and genetic backgrounds may have a more prominent role than human polyomaviruses in the development of bladder cancer in South of Iran.