Higher Risk Of Bladder Cancer Research Articles

Sex differences in the risk of bladder cancer among kidney transplant recipients and patients with kidney failure receiving hemodialysis: a nationwide cohort study.

Although both patients with kidney failure (KF) receiving hemodialysis (HD) and kidney transplant (KT) recipients (KTRs) have a high risk of bladder cancer, how this risk changes in the transition from dialysis to KT is unknown. In this study, we aimed to investigate the risk of bladder cancer in KTRs and patients on HD. This was a nationwide longitudinal cohort study of 66,547 participants from the National Health Insurance Service cohort who started HD for KF or received KT from 2002 to 2020. The primary outcome was the diagnosis of bladder cancer, which was defined as the composite of diagnostic codes and either hospitalization or ≥2 outpatient visits for bladder cancer. During mean follow-ups of 4.2 and 7.9 years in the HD and KT groups, respectively, the incidence rates of bladder cancer were 1.1/1,000 and 0.3/1,000 person-years, respectively. In the time-dependent multivariable Cox models, compared to patients on HD, the adjusted hazard ratio (aHR) for bladder cancer among KTRs was 0.36 (95% confidence interval [CI], 0.21-0.60; p<0.001). Among men, this aHR was 0.29 (95% CI, 0.15-0.55; p<0.001); however, no statistically significant association between the kidney replacement therapy modality and the risk of bladder cancer was observed among women. Landmark analysis performed to avoid immortal time bias by redefining time zero as a specific landmark time (2 and 5 years after HD initiation or KT) revealed similar results. The risk of bladder cancer was significantly lower among KTRs than that among patients receiving HD, particularly among men.

Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004–2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

Risk of bladder cancer in patients with type 2 diabetes mellitus: a retrospective population-based cohort study in Lithuania

PurposeThe objective of our study was to evaluate bladder cancer risk among Lithuanian type 2 diabetes mellitus (T2DM) patients and the effect of antihyperglycemic therapy on bladder cancer risk.MethodsWe analyzed bladder cancer risk in a cohort of patients who were diagnosed with T2DM between 2001 and 2012 in Lithuania. Bladder cancer risk in four groups of antihyperglycemic medication users (insulin-only, metformin-only, sulfonylurea-only, and pioglitazone ± any other drug) was also assessed. Standardized incidence ratios for bladder cancer were calculated.ResultsA total of 76,818 patients (28,762 males and 48,056 females) with T2DM were included in the final cohort. In the whole cohort of diabetic patients, 277 bladder cancer cases were observed, compared to 232.75 expected cases, according to bladder cancer rates in the general population (Standardized Incidence Ratio 1.19; 95% Confidence Interval: 1.06–1.34). Higher risk of bladder cancer was found in both men and women; however, in women the risk increase was not statistically significant. We found higher risk of bladder cancer in patients of both sexes diagnosed with T2DM at the age of 50–79 years and also in all groups of different antihyperglycemic medication users.ConclusionT2DM was associated with increased risk of bladder cancer.

Association Between Bladder Cancer and Environmental Risk Factors in Guilan Province: A Case-Control Study

Background: Occupational settings expose workers to various substances linked to cancer risk, influenced by exposure intensity and duration. Considering the diverse work conditions across Iranian cities and the unexplored link between occupation and bladder cancer (BC) in Guilan Province, identifying high-risk occupations and industries is imperative for implementing preventive measures in the region. Objectives: To investigate the effect of people's occupations on bladder cancer in Guilan Province. Methods: The study encompassed 266 diagnosed BC patients in Guilan Province who received treatment at local healthcare centers, along with 191 control individuals aged 18 and over. Data for the cases were meticulously recorded in medical records at the Guilan Cancer Registry. The same checklists, including demographic characteristics, comorbidities, addiction status, water consumption habits, environmental exposures, current and previous occupation, previous history of cancer, and family history of cancer, were recorded for the controls. Odds ratios and their 95% confidence intervals were estimated using adjusted logistic regression (LR). Results: The study found that the odds ratio of bladder cancer (BC) was 2.80 (95% CI: 1.26 - 6.21) for the age group 60 - 70 years and 18.2 (95% CI: 7.31 - 45.6) for individuals above 70 years. Rural dwelling increased the risk by 5.06-fold, while well water consumption and regular opium use amplified it by 6.12-fold and 2.58-fold, respectively. Exposure to tar and carbon derivatives led to a 3.53-fold increase in risk, and exposure to combustion/greenhouse gases showed a 10.72-fold increase. Chemical-related occupations, tar, carbon derivatives, smoking, and opium consumption were significant risk factors. Conclusions: Occupations involving chemical substances such as greenhouse gases, tar, and carbon derivatives are associated with a higher risk of bladder cancer (BC). Furthermore, smoking, opium use, and well water consumption significantly elevate the risk of this cancer.

Association of Pro-Inflammatory Diet, Smoking, and Alcohol Consumption with Bladder Cancer: Evidence from Case-Control and NHANES Studies from 1999 to 2020.

Diet might be a modifiable factor in preventing cancer by modulating inflammation. This study aims to explore the association between the dietary inflammatory index (DII) score and the risk of bladder cancer (BC). A total of 112 BC patients and 292 control subjects were enrolled in a case-control trial. Additionally, we tracked a total of 109 BC patients and 319 controls, whose propensity scores were obtained from the Nutrition Examination Survey (NHANES) database spanning from 1999 to 2020. The baseline index and dietary intake data were assessed using a food frequency questionnaire (FFQ). DII scores were calculated based on the dietary intake of 20 nutrients obtained from participants and categorized into four groups. The association between the inflammatory potential of the diet and BC risk was investigated using multivariate odds ratios (ORs) and 95% confidence intervals (CIs). High DII scores were associated with a pro-inflammatory diet and a higher risk of BC, with higher DII scores positively associated with a higher risk of BC (quartiles 4 vs. 1, ORs 4.89, 95% CIs 2.09-11.25 p < 0.001). Specifically, this might promote BC development by inducing oxidative stress and affecting DNA repair mechanisms. This result was consistent with the NHANES findings (quartiles 4 vs. 1, ORs 2.69, 95% CIs 1.25-5.77, p = 0.006) and further supported the association of pro-inflammatory diet and lifestyle factors with the risk of BC. Diets with the highest pro-inflammatory potential were associated with an increased risk of BC. By adjusting lifestyle factors, individuals might effectively lower their DII, thereby reducing the risk of developing BC. The results are consistent with the NHANES cohort.

Racial and gender disparities in the incidence of bladder cancer: A nationwide analysis.

e16623 Background: Several studies have been conducted to examine racial and gender disparities in various common malignancies. However, there remains a notable lack of comprehensive data addressing ethnic and gender disparities, specifically in relation to patients with Bladder cancer. This study sought to evaluate these disparities and their potential impact on the risk of developing bladder cancer. Methods: Using the National Inpatient Sample 2020, we identified patients diagnosed with Bladder cancer as their primary condition (local/regional and advanced metastatic).We analyzed disparities in the baseline characteristics, including age, gender, insurance status, income, comorbidities, and the risk associated with Bladder cancer. We utilized a log Binomial regression model to determine the risk ratios after adjusting for any confounding variables. Results: A total of 6,471,165 patients were analyzed, and it was found that 24,400 of them (0.4%) had bladder cancer. Among these patients, 76% were male, and 23% were female, p&lt;0.001.The mean age of patients with and without Bladder cancer was 72(SD +/- 11.39) vs. 49(SD+/- 27.18) years, respectively, p&lt;0.001. Female patients demonstrated a lower risk of developing bladder cancer than males (RR=0.31(0.24-0.27); p&lt;0.001). Compared to white females, white and black males exhibited an increased risk of bladder cancer (RR=3.45(3.20-3.73); p&lt;0.001 and RR=1.71(1.48-1.98); p&lt;0.001, respectively). Hispanic males also showed an increased risk (RR=2.20(1.88-2.58); p&lt;0.001), while Hispanic females demonstrated a decreased risk (RR=0.72(0.56-0.94); p=0.016). Males of other races had a higher risk of bladder cancer (RR=2.95(2.36-3.70); p&lt;0.001), and no significant difference was observed in the risk of bladder cancer in Asian males and females (RR=1.39(0.66-2.92); p=0.384 and RR=0.83(0.34-2.01); p=0.694, respectively). The risk of bladder cancer increased with age (36-45: RR=4.45(2.21-8.96),p&lt;0.001,46-64: RR=10.94(5.67-21.12),p&lt;0.001, &gt;65: RR =21.02(10.87-40.63), p&lt;0.001). Conclusions: Disparities in healthcare access and understanding of specific challenges faced by high-risk groups deeply impact patients with bladder cancer. Gaining a deeper knowledge of these disparities can better support this vulnerable patient population and illuminate effective preventive measures for reducing the incidence of bladder cancer among high-risk demographic segments.

Clinical characteristics and molecular mechanisms underlying bladder cancer in individuals with spinal cord injury: a systematic review

BackgroundPatients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of aggressiveness of malignancy is high. Most of the literature is based on disease clinical features while, our study reviews the clinical characteristics and molecular mechanisms of spinal cord injury patients with bladder cancer, so that it might help clinicians better recognize and manage these patients.MethodWe searched PubMed, Web of Science and Embase, using retrieval type like (“Neurogenic Lower Urinary Tract Dysfunction” OR “Spinal cord injury” OR “Spinal Cord Trauma”) AND (“bladder cancer” OR “bladder neoplasm” OR “bladder carcinoma” OR “Urinary Bladder Neoplasms” OR “Bladder Tumor”). In Web of Science, the retrieval type was searched as “Topic”, and in PubMed and Embase, as “All Field”. The methodological quality of eligible studies and their risk of bias were assessed using the Newcastle-Ottawa scale. This article is registered in PROSPERO with the CBD number: CRD42024508514.ResultIn WOS, we searched 219 related papers, in PubMed, 122 and in Embase, 363. Thus, a total of 254 articles were included after passing the screening, within a time range between 1960 and 2023. A comprehensive analysis of the data showed that the mortality and incidence rates of bladder cancer in spinal cord injury patients were higher than that of the general population, and the most frequent pathological type was squamous cell carcinoma. In parallel to long-term urinary tract infection and indwelling catheterization, the role of molecules such as NO, MiR 1949 and Rb 1. was found to be crucial pathogenetically.ConclusionThis review highlights the risk of bladder cancer in SCI patients, comprehensively addressing the clinical characteristics and related molecular mechanisms. However, given that there are few studies on the molecular mechanisms of bladder cancer in spinal cord injury, further research is needed to expand the understanding of the disease.

Abstract 832: Gender differences in urinary tract cancer susceptibility associated with radon in water: A population based study from Finland

Abstract Background: Radon as a common source of environmental radiation, while its carcinogenic effect on urinary tract cancer has not been fully investigated. Methods: Men and women who have continuously lived in Finland from year 1987 onward and reached 40+ years old at the beginning of 2017 were followed up for urinary tract cancer, including bladder cancer (ICD-O 3 code C67) and kidney cancer (C64-C66 and C68) for 5 years until the end of 2021. The residential location and type of buildings of the cohort members were traced from year 1987 until 2016 annually and linked to the average cumulative exposure of radon concentration in well water on municipality level. Newly diagnosed UTC cases were identified based on the Finnish cancer register. Pre-existing health conditions, such as hypertension, diabetes, chronic kidney disease, calculus of kidney and lower urinary tract, family history of cancer, as well as socioeconomic factors were ascertained from multiple registry databases. Data were analyzed with Cox proportional hazards model conditional on birth cohorts and adjusted with available covariates. Findings: Among 1,019,331 men and 1,192,960 women with 30-years average radon exposure, 4206 and 2226 urinary tract cancer cases were diagnosed during follow-up period from 2017 until correspondingly. Men with higher radon exposure (&amp;gt;500 Bq/m3) had about 14% higher risks of UTC in total (HR 1.14, 95% CI 1.07-1.21), 19% higher risks of bladder cancer (HR 1.19, 95%CI 1.09-1.32), 10% higher risks of kidney cancer (HR 1.10, 95%CI 1.02-1.20) comparing with lower exposed samples. Women with higher radon exposure had about 1% higher risks of UTC in total (HR 1.01, 95%CI 0.93-1.10), 3% higher risks of bladder cancer (HR 1.03, 95%CI 0.88-1.22), 1% higher risks of kidney cancer (HR 1.01, 95%CI 0.92-1.11). In the sub-population who only lived in houses during the 30-years exposure period, men with higher radon exposure had about 24% higher risks of UTC (HR 1.24, 95% CI 1.12- 1.36), 30% higher risks of bladder cancer (HR 1.30, 95%CI 1.12-1.51), 20% higher risks of kidney cancer (HR 1.20, 95%CI 1.06-1.36). No significant association was observed in women who only lived in houses during exposure period. Conclusions: For men, higher radon exposure was significantly associated with elevated risks of UTC. No significant association was observed in women. Further investigates were needed to explore the mechanisms of gender differences in UTC susceptibility associated with radon exposure. Keywords: Radon, Radiation, Cancer, Urinary tract cancer, Kidney cancer, Bladder cancer Citation Format: Peng Yunzhi Li. Gender differences in urinary tract cancer susceptibility associated with radon in water: A population based study from Finland [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 832.

Genetic factors, adherence to healthy lifestyle behaviors, and risk of bladder cancer

BackgroundGenetic and lifestyle factors both contribute to the pathogenesis of bladder cancer, but the extent to which the increased genetic risk can be mitigated by adhering to a healthy lifestyle remains unclear. We aimed to investigate the association of combined lifestyle factors with bladder cancer risk within genetic risk groups.MethodsWe conducted a prospective study of 375 998 unrelated participants of European ancestry with genotype and lifestyle data and free of cancer from the UK biobank. We generated a polygenic risk score (PRS) using 16 single nucleotide polymorphisms and a healthy lifestyle score based on body weight, smoking status, physical activity, and diet. Cox models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of genetic and lifestyle factors on bladder cancer.ResultsDuring a median follow-up of 11.8 years, 880 participants developed bladder cancer. Compared with those with low PRS, participants with intermediate and high PRS had a higher risk of bladder cancer (HR 1.29, 95% CI 1.07–1.56; HR 1.63, 95% CI 1.32–2.02, respectively). An optimal lifestyle was associated with an approximately 50% lower risk of bladder cancer than a poor lifestyle across all genetic strata. Participants with a high genetic risk and a poor lifestyle had 3.6-fold elevated risk of bladder cancer compared with those with a low genetic risk and an optimal lifestyle (HR 3.63, 95% CI 2.23 –5.91).ConclusionsAdhering to a healthy lifestyle could substantially reduce the bladder cancer risk across all genetic strata, even for high-genetic risk individuals. For all populations, adopting an intermediate lifestyle is more beneficial than a poor one, and adhering to an optimal lifestyle is the ideal effective strategy for bladder cancer prevention.

Secondary Primary Cancer Risk After Radiation Therapy in Rectal Cancer: A Population-Based Cohort Study With Propensity Score Matching

BackgroundIt remains unclear whether radiation therapy (RT) has an impact on the development of secondary primary cancer (SC) in rectal cancer (RC) patients, especially within the true pelvis. AimTo examine the incidence of SC in a population-based cohort of RC after surgical treatment with or without radiation therapy (RT, NRT). Patients and MethodsThe epidemiological cohort consisting of 13,919 RC patients with primary M0 stage diagnosed between 1998 and 2019 was collected from cancer registry data of Upper Bavaria. Competing risk analyses were conducted regarding the development of SC on 11 687 first malignancies, stratified by RT/NRT. A propensity score (PS) was generated by logistic regression modeling of RT to repeat competing risk analyses on a PS-matched cohort. ResultsThe median age (interquartile range) of the epidemiological cohort was 68.9 years (60.4-76.7). About 60.8%, were men, 38.7% had UICC III, 35.8% of tumors were localized lower than 8 cm, 41.3% underwent RT. Only 17.1% of patients older than 80 years at diagnosis received RT. In general, RT patients were 5 years younger than NRT patients (65.9 years [58.0-73.0] vs. 71.3 years [62.4-79.2], P < .0001). The 20-year cumulative incidence of SC was 16.5% in RT and 17.4% in NRT patients (P = .2298). Men with RT had a lower risk of prostate cancer (HR = 0.55, 95%CI [0.34-0.91], P = .0168). In the PS-matched cohort, RT patients had a significantly higher risk of bladder cancer during follow-up (10-year cumulative incidence of 1.1% vs. 0.6% in NRT). The direction of the RT effects in men and women and different tumor sites may cancel each other. ConclusionA protective effect of RT in rectal cancer patients on developing prostate SC by half is reproduced. Further analyses studying the long-term SC risks of RT should essentially focus on stratification by sex, and focus on more recent data.

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.

The association between pioglitazone consumption and incidence of bladder cancer in type II diabetic patients: a systematic review and meta-analysis of observational studies

Background: Bladder cancer is the single most prevalent urinary tract malignancy in humans with a higher risk in diabetic patients. Pioglitazone is among the conventional antidiabetic drugs. The present study thus seeks to investigate the association between the administration of pioglitazone and the incidence of bladder cancer in type II diabetic patients through a meta-analysis and systematic analysis. Materials and Methods: International databases including Web of Science, Medline/PubMed, Scopus, and Google Scholar search engine were explored. To integrate the results of studies odds ratio (OR), risk ratio (RR) or hazard ratio (HR) logarithm was extracted from each study, and the I2 index or the Cochran’s Q test were conducted to examine the heterogeneities across studies. Data analysis was carried out in STATA version14 considering a significance level of p&lt;0.05. Results: The 15 examined studies had investigated a total of 5,353,528 patients (1,536,723 patients in case groups and 3,816,805 patients in control groups). The relative risk of bladder cancer was [RR: 1.20 (95% CI: 1.09-1.32)] in pioglitazone users. Bladder cancer risk in pioglitazone users was higher by [RR: 1.14 (95% CI: 1.03-1.25)] compared to those who had never taken pioglitazone, [RR: 1.32 (95% CI: 1.02-1.70] compared to sulfonylurea users, and [RR: 1.57 (95% CI: 1.23-2)] compared to dipeptidyl peptidase-4 (DPP-4) users. Moreover, the relative risk between pioglitazone consumption and bladder cancer was reported to be [RR: 1.27 (95% CI: 0.96-1.68)] in patients with a follow-up shorter than five years and [RR: 1.24 (95% CI: 1.09-1.41)] is patients with a follow-up of five years or longer. On the other hand, the relative risk between pioglitazone consumption and bladder cancer was [RR: 1 (95% CI: 0.69-1.45)] in 50-59 age group, [RR: 1.20 (95% CI: 1.04-1.38)] in the 60-69 age group, and [RR: 1.33 (95% CI: 1.14-1.56)] in the 70-79 age group. Conclusion: Patients who receive pioglitazone had a 20% higher risk of bladder cancer compared to those who had not taken pioglitazone or prescribed other medication such as sulfonylurea and DPP-4s. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID: CRD42023391151).

Increased Burden of Second Bladder Cancer and Rectal Cancer in Prostate Cancer Treated With Radiotherapy: Results From Surveillance, Epidemiology, and End Results.

Previous studies have confirmed the higher risk of bladder cancer (BC) and rectal cancer (RC) development among prostate cancer (PCa) patients receiving radiotherapy. In this study, we intend to explore the long-term trend in second BC and RC incidence among PCa patients undergoing radiotherapy. We identified first primary PCa patients diagnosed between 1975 and 2014 from the Surveillance, Epidemiology, and End Results (SEER)-9 cancer registries. Standardized incidence ratios (SIRs) were calculated by calendar year of diagnosis among PCa patients receiving radiotherapy and not. P trends were evaluated using Poisson regression. 10-year cumulative incidence of BC and RC was calculated utilizing competing risk regression model. Of PCa patients treated with radiotherapy, SIRs of BC increased from .82 (95% CI: .35- 1.61) in 1980-1984 to 1.58 (95% CI: 1.48-1.68) in 2010-2014 (Ptrend=.003). SIRs of RC increased from 1.01 (95% CI: .27-2.58) in 1980-1984 to 1.54 (95% CI: 1.31-1.81) in 2010-2014 (Ptrend=.025). No statistically significant change in both BC and RC incidence was observed. The 10-year cumulative incidence of BC increased from 1975-1984 (.04%) to 2005-2014 (.15%) among PCa treated with radiotherapy. Simultaneously, the 10-year cumulative incidence of RC was demonstrated to range from 1975-1984 (.02%) to 2005-2014 (.11%). we have observed an increasing trend in second BC and RC incidence in PCa patients receiving radiotherapy. There was no significant change in the incidence of second BC and RC in PCa without radiotherapy. These results reflect the increasing clinical burden of second malignant tumors in PCa patients undergoing radiotherapy.

Genetically supported causality between benign prostate hyperplasia and urinary bladder neoplasms: A mendelian randomization study.

Background: Observational studies have suggested a possible association between benign prostate hyperplasia (BPH) and bladder cancer (BLCA). However, these studies are prone to errors and limitations or confounding factors, making them unsuitable for assessing the causal relationship between BPH and BLCA. Objective: Two-sample Mendelian randomization (MR) was performed to determine a possible association between genetically predicted BPH and the risk of BLCA. Methods: A two-sample MR analysis was performed utilizing the Integrative Epidemiology Unit genome-wide association (GWAS) database of the Medical Research Council, United Kingdom A series of control steps, including five primary methods, were performed to identify the most suitable instrumental variables (IVs) for MR analysis. Sensitivity analysis was conducted to avoid statistical errors, including heterogeneity and pleiotropic bias. Results: Genetic variants associated with BPH (P < 5 × 10-8) and BLCA (P < 5 × 10-6) were identified as instrumental variables and assessed using GWAS summary data (BPH, 4,670 cases vs. 458,340 controls; BLCA, 1,279 cases vs. 372,016 controls). BPH exhibited a positive effect on the occurrence of BLCA (inverse variance weighted (IVW), odds ratio (OR) = 1.095, 95% confidence interval (CI) = 1.030-1.165, p = 0.003), but there was no causal effect for BLCA on BPH (IVW, OR = 1.092, 95% CI = 0.814-1.465, p = 0.554). Conclusion: Genetically predicted BPH was associated with a higher risk of BLCA in all histological subtypes. In contrast, the evidence was not significant to back the causality of genetically induced BLCA on BPH. These findings indicate that BPH plays a key role in developing BLCA in the European population. Further studies are needed to uncover the underlying mechanisms.

PSUN250 Empagliflozin Induced Bladder Cancer in an Adult Patient With Latent Autoimmune Diabetes

Abstract Sodium glucose cotransporter type 2 (SGLT2) inhibitor is a novel class of antidiabetic agent. The association of SGLT2 inhibitors and incidence of bladder cancer has not been well established due to few numbers of cases and not enough length of exposure. Here we describe a case of bladder cancer developed one year after empagliflozin exposure in a patient with latent autoimmune diabetes. Case description A 51-year-old man presented to our endocrine clinic with a one-year diagnosis of type 2 diabetes mellitus. His glycosylated hemoglobin (HbA1c) was 8% on maximum dose metformin and well adherence to diet. The patient had no significant past medical history and his body mass index was 23.6 kg/m2. Empagliflozin 25 mg daily was added to his regimen, in addition to sulfonylurea and dipeptidyl peptidase-4 (DPP-4) inhibitor drugs. The patient continued to have persistent hyperglycemia despite medical therapy with HbA1c ranged between 7.5-7.9%. After one year, he presented with fatigue, unintentional 7-kg weight loss and perianal pain. A transrectal ultrasound of the pelvis showed a 10-mm solid lesion in the urinary bladder. He underwent transurethral resection of bladder tumor; pathology showed a low grade papillary urothelial carcinoma with focal areas of high grade. Empagliflozin was discontinued and due to persistent hyperglycemia, further labs were requested. Fasting blood glucose of 265 mg/dl, HA1c of 7.9%, anti-GAD antibody was positive 37.52 u/ml (&amp;lt;10.0), C-peptide of 0.51 ng/ml (0.37-1.47), insulin of 2.0 mu/ml (2.6-24.9). These findings suggested latent autoimmune diabetes with mild pancreatic reserve. Patient was then started on insulin therapy of Glargine and Aspart. Conclusion The use of SGLT2 inhibitors in patients with autoimmune diabetes may have a higher risk of bladder cancer as compared to patients with type 2 diabetes. An individualized selection of antidiabetic agent with consideration of proper diagnosis is recommended to prevent a serious consequence. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population.

Bladder cancer (BCa) is an increasingly severe clinical and public health issue. Therefore, we aim to investigate BCa susceptibility loci in the Chinese population. In this study, 487 BCa patients and 563 controls were recruited from the First Affiliated Hospital of China Medical University from July 2015 to September 2020. A total of ten single-nucleotide polymorphisms (SNPs) in solute carrier family 15 member 1 (SLC15A1), CWC27 spliceosome associated cyclophilin (CWC27), or UDP glucuronosyltransferase family 1 member A3 (UGT1A3) genes were genotyped. The associations between the candidate SNPs and BCa were analyzed using genotype and haplotype analysis. The results demonstrated that Rs4646227 of SLC15A1 has a significant association with BCa. The patients with CG (OR =2.513, p < 0.05) and GG (OR =2.859, p < 0.05) genotypes had an increasing risk of BCa compared with the CC genotype. For the CWC27 gene, genotypic frequency analysis revealed that the GT or TT genotype of rs2042329 and the CT or TT genotype of rs1870437 were more frequent in BCa patients than those in the control group, indicating that these genotypes were associated with a higher risk of BCa (all p < 0.05). Haplotypes of SLC15A1, UGT1A3, and CWC27 genes found that the C-C-C haplotype of SLC15A1 was associated with a lower risk of BCa while the C-G-C haplotype was associated with a higher risk. For the UGT1A3 gene, a moderate protective effect was observed with the most frequent T-T-C haplotype, and for the CWC27 gene, most of the haplotypes showed no association with BCa, except the G-G-C-T haplotype (order of SNPs: rs2042329-rs7735338-rs1870437-rs2278351, OR =0.81, p =0.038). In sum, this study indicated that rs2042329 and rs1870437 in the CWC27 gene and rs4646227 in the SLC15A1 gene are independent indicators for BCa risk in Chinese people. Further large-scale studies are required to validate these findings. Also, this study provided the theoretical basis for developing new therapeutic drug targeting of BCa.

Pioglitazone use in Australia and the United Kingdom following drug safety advisories on bladder cancer risk: An interrupted time series study

PurposeNational regulators in Australia and the United Kingdom issued safety advisories on the association between pioglitazone use and bladder cancer in July 2011. The Australian advisory noted that males were at higher risk of bladder cancer than females, while the UK advisory highlighted a new recommendation, suggest careful consideration in the elderly due to increasing risk with age. This study examined whether these differences in the advisories had different age‐ and sex‐based impacts in each country.MethodsInterrupted time series analysis was used to compare pioglitazone use (prescriptions/100000 population) in Australia and the United Kingdom for the 24 months before and 11 months after the July 2011 safety advisories (study period July 2009–June 2012). Separate models were used to compare use by sex and age group (≥65 years vs. <65 years) in each country.ResultsPioglitazone use fell in Australia (17%) and the United Kingdom (24%) following the safety advisories. Use of pioglitazone fell more for males (18%) than females (16%) in Australia, and more for females (25%) than males (23%) in the United Kingdom; however, neither difference was statistically significant (Australia p = 0.445, United Kingdom p = 0.462). Pioglitazone use fell to a similar extent among older people than younger people in the United Kingdom (23% vs. 26%, p = 0.354), and did not differ between age groups in Australia (both 18%, p = 0.772).ConclusionsThe results indicate that differences in the Australian and UK safety advisories resulted in substantial reductions in pioglitazone use at the population level in both countries, however, differences by sub‐groups were not observed.

Prevalence of Human Papilloma Virus Infection in Bladder Cancer: A Systematic Review.

The etiology of bladder cancer is known to be associated with behavioral and environmental factors. Moreover, several studies suggested a potential role of HPV infection in the pathogenesis with controversial results. A systematic review was conducted to assess the role of HPV. A total of 46 articles that reported the prevalence of HPV infection in squamous (SCC), urothelial (UC), and transitional cell carcinomas (TCC) were selected. A pooled prevalence of 19% was found, with a significant difference in SCC that was mainly driven by HPV-16. Moreover, infection prevalence in case-control studies showed a higher risk of bladder cancer in HPV-positive cases (OR: 7.84; p-value < 0.00001). The results may suggest an etiologic role of HPV in bladder cancer. HPV vaccine administration in both sexes could be key to prevent the infection caused by high-risk genotypes.

Diet quality, common genetic polymorphisms, and bladder cancer risk in a New England population-based study.

We examined the interaction between common genetic bladder cancer variants, diet quality, and bladder cancer risk in a population-based case-control study conducted in New England. At the time of enrollment, 806 bladder cancer cases and 974 controls provided a DNA sample and completed a diet history questionnaire. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010) score. Single nucleotide polymorphisms (SNPs) reported in genome-wide association studies to be associated with bladder cancer risk were combined into a polygenic risk score and also examined individually for interaction with the AHEI-2010. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. A 1-standard deviation increase in polygenic risk score was associated with higher bladder cancer risk (OR, 1.34; 95% CI 1.21-1.49). Adherence to the AHEI-2010 was not associated with bladder cancer risk (OR, 0.99; 95% CI 0.98-1.00) and the polygenic risk score did not appear to modify the association between the AHEI-2010 and bladder cancer risk. In single-SNP analyses, rs8102137 (bladder cancer risk allele, C) modified the association between the AHEI-2010 total score and bladder cancer risk, with the strongest evidence for the AHEI-2010 long chain fat guideline (OR for TT, 0.92; 95% CI 0.87-0.98; OR for CT, 1.02; 95% CI 0.96-1.08; OR for CC, 1.03; 95% CI 0.93-1.14; p for interaction, 0.02). In conclusion, rs8102137 near the cyclin E1 gene ( CCNE1 ) may be involved in gene-diet interactions for bladder cancer risk.

Gender and Age Differences of Genitourinary Cancers Among Chronic Dialysis Patients in Taiwan.

To investigate the age and gender differences among chronic dialysis patients who developed genitourinary cancers in Taiwan. Incident hemodialysis patients aged 20 years or older were selected for retrospective cohort study from the National Health Insurance Research Database between 2002 and 2015, and the Taiwan Cancer Registry Database between 2007 and 2015. A two-step approach was employed to find the respective matched controls of non-dialysis patients. Finally, 65,450 dialysis patients and 261,800 non-dialysis patients were matched for further analysis. New diagnosis of genitourinary cancers during follow-up was the primary outcome of interest. Dialysis was significantly associated with increased risk of all types of genitourinary cancers (P < .001), substantially within the first two years after dialysis initiation. Cox proportional hazard analysis showed a significantly increased hazard ratio (HR 6.58, 95% CI 6.05-7.16) among dialysis patients after multivariate adjustment, and the highest risk was bladder cancer (HR 7.85, 95% CI 6.97-8.84). Subgroup analysis showed younger dialysis patients (20-49 years old) had the highest risk of genitourinary cancer, especially females, in this subgroup with the highest risk of bladder cancer (HR 58.08, 95% CI 13.88-243.06). The risks of all site-specific genitourinary cancers were increased in chronic dialysis patients, especially in younger females. Developing different screening strategies for these high-risk patients is necessary. This study compared the effect of sex, age and dialysis duration on the susceptibility to develop genitourinary cancers in dialysis patients through the national health database linkage in Taiwan. We matched 65,450 dialysis patients and 261,800 non-dialysis patients for further analysis. Younger and female dialysis patients were at higher risk of kidney and bladder cancers.