Risk Of Bladder Cancer Research Articles

Arsenic in Drinking Water and Urinary Tract Cancers: A Systematic Review Update

Problem: There remains uncertainty around cancer risk at lower levels of arsenic in drinking water. This study updates evidence from our previous review on the relationship between arsenic in drinking water and urinary bladder and kidney cancers (updated search January 2013 to February 2023). Method: Thirty-four studies were retained for review; six met criteria for inclusion in meta-analysis. Risk estimates for bladder and kidney cancer incidence and mortality were analyzed separately using Bayesian multilevel linear models. Results: For bladder cancer incidence, the estimated posterior mean relative risks (RRs) were 1.25 (0.92–1.73), 2.11 (1.18–4.22) and 3.01 (1.31–8.17) at arsenic concentrations of 10, 50 and 150 μg/L, respectively, with posterior probabilities of 92%, 99% and 100%, respectively, for the RRs to be >1. The corresponding RRs for kidney cancer were 1.37 (1.07–1.77), 1.95 (1.44–2.65) and 2.47 (1.74–3.52), with posterior probabilities of 100%. For bladder cancer, the posterior mean mortality ratios were 1.36 (0.35–6.39), 2.92 (1.24–7.82) and 4.88 (2.83–9.03) with posterior probabilities of 72%, 99% and 100%, respectively. Conclusions: The findings show increased bladder and kidney cancer risks at lower levels of arsenic in drinking water. Given that many people worldwide are exposed to lower levels of arsenic in drinking water, the public health impacts are substantial.

Prediction of 6-year risk of bladder cancer using the HUNT Lung Cancer Risk Model in ever-smokers: A HUNT study.

e16581 Background: Bladder cancer is the 6th most common cancer in men and 17th most common cancer in women and the mortality is high when detected in advanced stage. Previous or current cigarette smoke is the main risk factor. There is no screening program for bladder cancer. Given the pathophysiological similarity with lung cancer, we postulated that a lung cancer risk model could work for bladder cancer. The validated HUNT Lung Cancer Risk Model (HUNT LCM) predicts lung cancer in 6 years with an area under the ROC curve (AUC) of 0.87. Here we aimed to test the performance of the HUNT LCM in the prospective HUNT2 cohort for a 6-year prediction of bladder cancer. Methods: The HUNT2 cohort from Norway, a prospective population study of 65 200 individuals 19-100 years of age, was followed up for a median of 15 years. This population was linked with the Norwegian Cancer Registry and all cases diagnosed with bladder cancer were registered. The HUNT Lung Cancer Model was used to predict risk of bladder cancer within 6 years. Results: In the HUNT2 cohort 38 846 ever-smokers were identified. 82.6% of those developing bladder cancer were ever-smokers. 31 269 had all the variables needed for the model and of those, 191 developed bladder cancer in six years. The HUNT Lung Cancer Model prediction of bladder cancer in 6 years AUC was 0.751. Conclusions: To our knowledge, this is the first time a lung cancer risk prediction model has been applied to predict bladder cancer. The performance of the model is lower than for lung cancer but still has a good performance. This may open a path for screening and early detection of bladder cancer.

Abstract 29: Detection of Protein Kinase C Isoenzymes in Patients at Risk of Schistosoma Haematobium Induced Bladder Cancer

Abstract Purpose: The Detection of Protein Kinase C Isoenzymes in Patients at risk of Schistosoma haematobium induced Bladder Cancer attending University of Maiduguri Teaching Hospital (UMTH) was carried out. The study comprised of fifty six (56) patients aged ten to fifty six (10-56) years with clinical features of schistosomiasis and confirmed for the presence of S .haematobium eggs in urine samples. Methods: Twenty milliliters (20ml) of urine was centrifuged at 1000 rpm for 10 min to obtain the sediment. The supernatants were then discarded and the sediment (pellet) re-suspended for S. haematobium. A drop of the sediment were transferred to a glass slide, covered with a cover slip and examined using × 40 objective lens. The urine samples were observed for red blood cells and deposits that might contain proteins. The extraction of total urine template RNA was carried out according to Bioneer Specification and protocol; fifty six (56) of the S. haematobium samples of the patients were used. AccuPrep® Universal RNA Extraction Kit (K-3141) from Bioneer Corporation was used and one page protocol was followed for RNA Extraction. Pre- Denaturation was done for 5min at 94oC, Denaturation for 30sec at 94oC, Annealing for 30sec at 52oC, Extension for 1min at 72oC 35 cycles, Final extension for 5min at 72oC. Results: Result was run on 2% agarose gel. The study was able to investigate and detect the putative involvement of different PKC isoforms (alpha, beta, and delta) in patient with risk of schistosoma related bladder cancer. Out of the fifty six (56) Multiplex PCR Amplification of PKC Alpha, PKC Beta and PKC Delta from cDNA of extracted RNA template of S. haematobium infected urine sample investigated, only twenty seven (27) showed detection base pairs predicted size from Lane 1-9; of which PKC Alpha (325bp) has two (2) lane; PKC Beta (490bp) has seven (7) lane; and PKC Delta (404bp) has eighteen (18) lane of predicted base pair according to the cDNA size marker, some empty-zero (0) bands lanes and Unpredicted base pair band size were also seen. Conclusion: The major findings in the present study were the detection of PKC isoenzymes base pairs (band) which indicated the risk level of schistoma induced bladder cancer and stages of the patients using the analysis that proves Isoenzymes are detected by electrophoresis. Snail control, sanitation, avoid contacts with bullinus species and focus on early detection and diagnosis of patients infected with S. haematobium. Citation Format: Zanna Abdulsalam, Adamu Inuwa, Sambo Bello Zailani. Detection of Protein Kinase C Isoenzymes in Patients at Risk of Schistosoma Haematobium Induced Bladder Cancer [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 29.

Log Odds of Positive Lymph Nodes (LODDS) as an Independent Predictor of Overall Survival Following Radical Cystectomy in Urothelial Bladder Cancer: Time to Rethink Conventional Node Staging.

Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscle-invasive bladder cancer (MIBC) and high risk non-MIBC. The American Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P-value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P=.009). Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC.

Risk of urinary tract cancers following arsenic exposure and tobacco smoking: a review.

Bladder cancer, prostate cancer, and kidney cancer, due to their high morbidity and mortality rates, result in significant economic and health care costs. Arsenic exposure affects the drinking water of millions of people worldwide. Long-term exposure to arsenic, even in low concentrations, increases the risk of developing various cancers. Smoking is also one of the leading causes of bladder, prostate and kidney cancers. Accordingly, this research reviews the relationship between arsenic exposure and smoking with three kinds of urinary tract cancers (bladder cancer, prostate cancer, and kidney cancer) due to their widespread concern for their negative impact on public health globally. In this review, we have gathered the most current information from scientific databases [PubMed, Scopus, Google Scholar, ISI web of science] regarding the relationship between arsenic exposure and tobacco smoking with the risk of bladder, prostate, and kidney cancer. In several studies, a significant relationship was determined between the incidence and mortality rate of the above-mentioned cancers in humans with arsenic exposure and tobacco smoking. The decrease or cessation of smoking and consumption of arsenic-free water significantly declined the incidence of bladder, prostate, and kidney cancers.

N -acetyltransferase 2 haplotype modifies risks for both dyslipidemia and urinary bladder cancer.

A novel haplotype in N -acetyltransferase 2 ( NAT2 ) composed of seven non-coding variants (rs1495741, rs4921913, rs4921914, rs4921915, rs146812806, rs35246381, and rs35570672) has been linked to dyslipidemia by multiple, independent genome-wide association studies. The haplotype is located approximately 14 kb downstream of NAT2-coding region (ch8:18,272,377-18,272,881; GRCh38/hg38) and represents a non-coding, intergenic haplotype. Interestingly, the same dyslipidemia NAT2 haplotype is also linked to urinary bladder cancer risk. Dyslipidemia risk alleles are associated with rapid acetylator phenotype, whereas bladder cancer risk alleles are associated with slow acetylator, suggesting that the level of systemic NAT2 activity modifies the risk of these pathologies. We speculate that rs1495741 (and its associated haplotype) belongs to a distal regulatory element of human NAT2 gene (e.g., enhancer or silencer), and the genetic variation at the newly discovered haplotype results in a differential level of NAT2 gene expression. Understanding how this NAT2 haplotype contributes to not only urinary bladder cancer but also to dyslipidemia will ultimately help devise strategies to identify and protect susceptible individuals.

Dietary vitamin D intake and the bladder cancer risk: A pooled analysis of prospective cohort studies

Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose-response relationships (Model 1) were examined using a nonparametric test for trend. In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HRhigh vitD, mod Ca, low P: 0.77, 95% CI: 0.59-1.00). No significant dose-response analyses were observed. The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.

LncRNA BCLET variant confers bladder cancer susceptibility through alternative splicing of MSANTD2 exon 1.

Alternative splicing (AS)-related single nucleotide polymorphisms (SNPs) are associated with risk of cancers, but the potential mechanism has not been fully elucidated. Two-stage case-control studies comprising 1630 cases and 2504 controls were conducted to investigate the association between the AS-SNPs and bladder cancer susceptibility. A series of assays were used to evaluate the functional effect of AS-SNPs on bladder cancer risk. We observed that SNP rs558814 A>G located in lncRNA BCLET (Bladder Cancer Low-Expressed Transcript, ENSG00000245498) can decrease the risk of bladder cancer (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.76-0.92, p = 3.26 × 10-4 ). Additionally, the G allele of rs558814 had transcriptional regulatory effects and facilitated the expression of BCLET transcripts, including BCLET-long and BCLET-short. We also found decreased BCLET expression in bladder cancer tissues and cells, and BCLET transcript upregulation substantially inhibited tumor growth of both bladder cancer cells and xenograft models. Mechanistically, BCLET recognized and regulated AS of MSANTD2 to participate in bladder carcinogenesis, preferentially promoting the production of MSANTD2-004. SNP rs558814 was associated with the expression of BCLET, which mainly increased the expression of MSANTD2-004 through AS of MSANTD2.

Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights

BackgroundGenomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. ObjectiveTo identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Design, setting, and participantsData from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. Outcome measurements and statistical analysesLog-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. Results and limitationsMultiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10−8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44–1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. ConclusionsWe report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. Patient summaryWe identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.

Physical activity, obesity, and bladder cancer incidence.

Cigarette smoking is an established risk factor for bladder cancer (BC), but evidence for physical inactivity and obesity is limited. This analysis included 146,027 participants from the Cancer Prevention Study-II (CPS-II) Nutrition Cohort, a large prospective cohort of cancer incidence established in 1992. Multivariable-adjusted Cox proportional hazards models were used to examine associations between body mass index (BMI), moderate-to-vigorous intensity aerobic physical activity (MVPA), leisure-time spent sitting, and BC risk. Effect modification by stage, smoking status, and sex was examined. Only participants accumulating 15.0- < 30.0 MET-hrs/wk of MVPA had a lower risk of BC overall (RR 0.88, 95% CI 0.78, 0.99, compared to > 0-7.5 MET-hrs/wk) in the fully adjusted models. When stratifying on BC stage, MVPA (15- < 30 MET-hrs/wk vs. > 0- < 7.5 MET-hrs/wk, RR 0.83, 95% CI 0.70-0.99) and excess sitting time (≥ 6h/day vs. 0- < 3h/day RR 1.22, 95% CI 1.02, 1.47) were associated with risk of invasive BC only. There was no consistent evidence for effect modification by smoking status or sex. This study supports that MVPA and sitting time may play a role in BC incidence, but associations likely differ by stage at diagnosis. While additional studies are needed to confirm associations by stage, this study adds to the evidence of the importance of being physically active for cancer prevention.

Causal associations of hyperthyroidism with prostate cancer, colon cancer, and leukemia: a Mendelian randomization study.

Observational studies have shown that hyperthyroidism may increase the risk of cancer, but their causal effects and direction are unclear. We conducted a two-sample Mendelian randomization (MR) study to explore the associations between genetic predisposition to hyperthyroidism and nine common types of cancer, including prostate, lung, breast, colon, leukemia, brain, skin, bladder, and esophagus cancer. We obtained summary statistics of hyperthyroidism and nine types of cancers from genome-wide association studies (GWAS). MR analysis is performed to investigate the potential causal relationship between hyperthyroidism and cancers. The inverse variance weighted (IVW) as the primary method was carried out. The robustness of the results was evaluated by sensitivity analysis. Genetically predicted hyperthyroidism was associated with a declining risk of occurrence of prostate cancer (odds ratio (OR)IVW= 0.859, P= 0.0004; OR MR-Egger=0.828, P= 0.03; OR weighted median= 0.827, P=0.0009). Additionally, there was a significant association between genetically predicted hyperthyroidism and colon cancer (OR IVW= 1.13, P= 0.011; OR MR-Egger= 1.31, P= 0.004; OR weighted median= 1.18, P= 0.0009). Hyperthyroidism was also suggestively correlated with a higher risk of leukemia based on the result of IVW and weighted median (OR IVW= 1.05, P= 0.01; OR weighted median= 1.08, P= 0.001). Results from a two-sample MR analysis suggested that hyperthyroidism was not associated with the risk of lung cancer, breast cancer, brain cancer, skin cancer, bladder cancer, and esophageal cancer. Our study provides evidence of a causal relationship between hyperthyroidism and the risk of prostate cancer, rectal cancer, and leukemia. Further research is needed to clarify the associations between hyperthyroidism and other cancers.

Food groups and urologic cancers risk: a systematic review and meta-analysis of prospective studies.

To assess the association between 12 food groups intake and the risk of urologic cancers. We scanned PubMed and Web of Science databases up to April 1st, 2023, and 73 publications met the inclusion criteria in the meta-analysis. We used a random effects model to estimate the summary risk ratios (RRs) and 95% confidence intervals (95% CI). In the linear dose-response meta-analysis, an inverse association was found between each additional daily 100 g of fruits [RR: 0.89, 95%CI = (0.83, 0.97)], 100 g of vegetables [RR: 0.92, 95%CI = (0.85, 0.99)], 12 g of alcohol [RR: 0.91, 95%CI = (0.88, 0.94)] and 1 cup of coffee [RR: 0.95, 95%CI = (0.83, 0.97)] intake and the risk of renal cell carcinoma. Conversely, each additional daily 100 g of red meat intake was positively associated with renal cell carcinoma [RR: 1.41, 95%CI = (1.03, 2.10)]. Inverse associations were observed between each additional daily 50 g of egg [RR: 0.73, 95%CI = (0.62, 0.87)] and each additional daily 1 cup of tea consumption and bladder cancer risk [RR: 0.97, 95%CI = (0.94, 0.99)]. There were no significant associations for nonlinear dose-response relationships between 12 food groups and urological cancers. Our meta-analysis strengthens the evidence that appropriate intake of specific food groups, such as fruits, vegetables, alcohol, tea, and coffee, is associated with the risk of renal cell carcinoma or bladder cancer. More studies are required to fill the knowledge gap on the links between various food groups and urologic cancers because the evidence was less credible in this meta-analysis. This study was registered on PROSPERO (CRD42022340336).

Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

The antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored. To assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression. This cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023. Newly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled. The primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis. The study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group. Results of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.

Risks of Bladder Cancer in Patients with Childhood Augmentation or Chronic Catheters for Neurogenic Bladder

Risks of Bladder Cancer in Patients with Childhood Augmentation or Chronic Catheters for Neurogenic Bladder

Inhibition of TNF-α Oncogene Expression by Artemisia Annua L. Extract Against Pioglitazone Side Effects in Male Albino Mice.

Pioglitazone (Actos) is one of the most recent oral antidiabetic drugs for treating the second type of diabetes mellitus as a common chronic and lifelong disease, but with harmful side effects. The objective of this study is to evaluate the effectiveness of Artemisia annua L. extract against the Actos drug side effects in the male albino mice. In present study, the use of Actos drug alone induced hepatotoxicity, renal inflammation, hematological disorders and bladder cancer, which are manifested by biochemical abnormalities and histopathological changes, moreover, the severity of toxicity depends on its dose. In contrast, the concurrent treatment with both Actos drug (45mg/kg) and Artemisia extract (4g/kg) was effective against the harmful side effects of the Actos drug. Where, the biochemical, hematological and histopathological investigations showed that the hepatotoxicity, renal inflammation, hematological disorders and histopathological changes were improved using combination of Actos and Artemisia extract. In addition, the results of TNF-ɑ oncogene expression levels in bladder tissues were significantly decreased by about 99.99% using the mix of both Actos drug and Artemisia extract. In conclusion, these findings reveal that the Artemisia annua extract on TNF-ɑ oncogene expression level is very significant and effective natural product against harmful side effects of pioglitazone which associated with an increased risk of incidentbladder canceramongpeople, but for application more studies must be achieved in that field.

Bladder cancer risk in relation to occupations held in a nationwide case-control study in Iran.

Globally, bladder cancer has been identified as one of the most frequent occupational cancers, but our understanding of occupational bladder cancer risk in Iran is less advanced. This study aimed to assess the risk of bladder cancer in relation to occupation in Iran. We used the IROPICAN case-control study data including 717 incident cases and 3477 controls. We assessed the risk of bladder cancer in relation to ever working in major groups of the International Standard Classification of Occupations (ISCO-68) while controlling for cigarette smoking, opium consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). In men, decreased ORs for bladder cancer were observed in administrative and managerial workers (OR 0.4; CI: 0.2, 0.9), and clerks (OR 0.6; CI: 0.4, 0.9). Elevated ORs were observed in metal processors (OR 5.4; CI: 1.3, 23.4), and workers in occupations with likely exposure to aromatic amines (OR 2.2; CI: 1.2, 4.0). There was no evidence of interactions between working in aromatic amines-exposed occupations and tobacco smoking or opium use. Elevated risk of bladder cancer in men in metal processors and workers likely exposed to aromatic amines aligns with associations observed outside Iran. Other previously confirmed associations between high-risk occupations and bladder cancer were not observed, possibly due to small numbers or lack of details on exposure. Future epidemiological studies in Iran would benefit from the development of exposure assessment tools such as job exposure matrices, generally applicable for retrospective exposure assessment in epidemiological studies.

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan.

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99-2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46-3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype-phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.

Interethnic Differences in Bladder Cancer Incidence and the Association between Type 2 Diabetes and Bladder Cancer in the Multiethnic Cohort Study.

Research on the association between type 2 diabetes (T2D) and bladder cancer (BCA) risk among non-European ancestry populations is sparse to nonexistent, and most prior studies rely on a single baseline assessment of T2D status. We estimated the T2D-BCA association using the Multiethnic Cohort Study of 185,059 men and women in California and Hawaii. Participants were African American, European American, Japanese American, Latin American, and Native Hawaiian, ages 45-75 years at enrollment (1993-1996). T2D was assessed by self-report at baseline, follow-up surveys, and Medicare claims. Cases were identified using Surveillance, Epidemiology and End Results Program cancer registries through 2016. Associations were estimated by race/ethnicity using Cox proportional hazards regression. Adjusted attributable fractions (AAF) and cumulative absolute risk of bladder cancer were estimated across groups. Over an average 19.7 years of follow-up 1,890 incident bladder cancer cases were diagnosed. Time-varying T2D was associated with bladder cancer in the multiethnic sample (HR = 1.17; 95% confidence interval, 1.05-1.30); however, the HR did not differ by race/ethnicity (P = 0.85). The AAF was 4.2% in the multiethnic sample and largest among Native Hawaiians (9.8%). Absolute risk of bladder cancer among European Americans without T2D was higher than all other groups with T2D. T2D is significantly associated with bladder cancer risk in a multiethnic sample. Those with T2D have higher incidence of bladder cancer, regardless of racial/ethnic group. Reducing T2D prevalence could substantially lower bladder cancer incidence among Native Hawaiians due to T2D being more common in this group. High absolute risk of bladder cancer among European Americans, regardless of T2D status, indicates that elevated bladder cancer risk in this group may be due to factors other than T2D. Future studies must explore reasons for this difference in incidence.

Human papillomaviruses and bladder cancer risk: first report in south of Iran.

The online version contains supplementary material available at 10.1007/s13337-023-00819-w.

Mutation Hotspots Found in Bladder Cancer Aid Prediction of Carcinogenic Risk in Normal Urothelium.

More than 80,000 new cases of bladder cancer are estimated to be diagnosed in 2023. However, the 5-year survival rate for bladder cancer has not changed in decades, highlighting the need for prevention. Numerous cancer-causing mutations are present in the urothelium long before signs of cancer arise. Mutation hotspots in cancer-driving genes were identified in non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) tumor samples. Mutation burden within the hotspot regions was measured in normal urothelium with a low and high risk of cancer. A significant correlation was found between the mutation burden in normal urothelium and bladder cancer tissue within the hotspot regions. A combination of measured hotspot burden and personal risk factors was used to fit machine learning classification models. The efficacy of each model to differentiate between adjacent benign urothelium from bladder cancer patients and normal urothelium from healthy donors was measured. A random forest model using a combination of personal risk factors and mutations within MIBC hotspots yielded the highest AUC of 0.9286 for the prediction of high- vs. low-risk normal urothelium. Currently, there are no effective biomarkers to assess subclinical field disease and early carcinogenic progression in the bladder. Our findings demonstrate novel differences in mutation hotspots in NMIBC and MIBC and provide the first evidence for mutation hotspots to aid in the assessment of cancer risk in the normal urothelium. Early risk assessment and identification of patients at high risk of bladder cancer before the clinical presentation of the disease can pave the way for targeted personalized preventative therapy.