Elevated Bladder Cancer Risk Research Articles

The Significant Associations between Epigenetic Clocks and Bladder Cancer Risks.

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for each clock. We discovered that higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR = 1.69 per SD increase, 95% CI, 1.44-1.98, p = 1.56 × 10-10 and OR = 1.09 per SD increase, 95% CI, 1.00-1.19, p = 0.04, respectively). Employing a summary statistics-based Mendelian randomization (MR) method, inverse-variance weighting (IVW), we found consistent risk estimates for bladder cancer with both HannumAge and HorvathAge. Sensitivity analyses using weighted median analysis and MR-Egger regression further supported the validity of the IVW method. However, GrimAge and PhenoAge were not associated with bladder cancer risk. In conclusion, our data provide the first evidence that accelerated biological aging is associated with elevated bladder cancer risk.

Association Between CYP24A1 Polymorphisms and Bladder Cancer Risk in the Chinese Han Population.

In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.

Assessing the Causal Relationship between Waterpipe Smoking and Bladder Cancer.

Rates of waterpipe use increase with very little data reporting any potential health consequences. The current study, a large case-control study, of 4,194 patients from Iran denotes an elevated risk of bladder cancer in exclusive waterpipe smokers compared with non-users. Additional studies are needed to further understand the risk waterpipe smoking has on bladder cancer. See related article by Hadji et al., p. 509.

A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer

Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case–control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine–phosphate–guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59–0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63–0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation.

Exploring the Relationship between CLPTM1L-MS2 Variants and Susceptibility to Bladder Cancer.

CLPTM1L (Cleft Lip and Palate Transmembrane Protein 1-Like) has previously been implicated in tumorigenesis and drug resistance in cancer. However, the genetic link between CLPTM1L and bladder cancer remains uncertain. In this study, we investigated the genetic association of variable number of tandem repeats (VNTR; minisatellites, MS) regions within CLPTM1L with bladder cancer. We identified four CLPTM1L-MS regions (MS1~MS4) located in intron regions. To evaluate the VNTR polymorphic alleles, we analyzed 441 cancer-free controls and 181 bladder cancer patients. Our analysis revealed a higher frequency of specific repeat sizes within the MS2 region in bladder cancer cases compared to controls. Notably, 25 and 27 repeats were exclusively present in the bladder cancer group. Moreover, rare alleles within the medium-length repeat range (25-29 repeats) were associated with an elevated bladder cancer risk (odds ratio [OR] = 5.78, 95% confidence interval [CI]: 1.49-22.47, p = 0.004). We confirmed that all MS regions followed Mendelian inheritance, and demonstrated that MS2 alleles increased CLPTM1L promoter activity in the UM-UC3 bladder cancer cells through a luciferase assay. Our findings propose the utility of CLPTM1L-MS regions as DNA typing markers, particularly highlighting the potential of middle-length rare alleles within CLPTM1L-MS2 as predictive markers for bladder cancer risk.

Modeling Historic Arsenic Exposures and Spatial Risk for Bladder Cancer.

Arsenic is a bladder carcinogen though less is known regarding the specific temporal relationship between exposure and bladder cancer diagnosis. In this study, we modeled time-varying mixtures of arsenic exposures at many historic temporal windows to evaluate their association with bladder cancer risk in the New England Bladder Cancer Study. We used arsenic exposure estimates up to 60 years prior to study entry and compared the goodness of fit of models using these mixtures to those using summary measures of arsenic exposures. We used the Bayesian index low rank kriging multiple membership model (LRK-MMM) to estimate the associations of these mixtures with bladder cancer and estimate cumulative spatial risk for bladder cancer using participants' residential histories. We found consistent evidence that modeling arsenic exposures as a time-varying mixture provided better fit to the data than using a single arsenic exposure summary measure. We estimated several positive though not significant associations of the time-varying arsenic mixtures with bladder cancer having odds ratios (ORs) of 1.03-1.14 and identified many significant and positive associations for an interaction among those who consumed water from a private dug well (ORs 1.28-1.60). Arsenic exposures 40-50 years before study entry received elevated importance weights in these mixtures. Additionally, we found two small areas of elevated cumulative spatial risk for bladder cancer in southern New Hampshire and in south central Maine. These results emphasize the importance of considering time-varying mixtures of exposures for diseases with long latencies such as bladder cancer.

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.

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.

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.

Abstract 4207: Systematic review and meta-analysis of cancer incidence after blood transfusion in the general population

Abstract Background: The impact of blood transfusion on cancer survival and mortality has been widely studied. However, few studies have investigated its relationship with cancer incidence. This is the first systematic review and meta-analysis evaluating the correlation between blood transfusion and cancer incidence. Methods: Five studies were identified through Pubmed, Embase, and Cochrane library. Four cohort studies and one case-control study (N = 3,048,906) were included. Over seventy percent were female (N =2,167,580), and about thirty-one percent (N = 956,522) were transfused. Meta-analysis was conducted between blood transfusion and cancer incidence. Subgroup analyses were performed by cancer types, follow-up period, and units of transfused blood. We pooled available risk estimates, which were adjusted for confounding factors, including age and sex, were pooled. Results: Overall cancer risk increased statistically significantly in people who received transfusion compared to the population that did not (1.70, 95% CI, 1.30 to 2.10). The result was consistent regardless of time intervals from transfusion or units of transfused blood. Cancer incidences in all solid tumors, except breast, thyroid, and uterine cancer, were higher in blood transfusion recipients (Table 1). The elevated risk of stomach, bladder, and kidney cancer was sustained for up to fifteen years. Furthermore, lung cancer, liver cancer, and non-Hodgkin lymphoma risk remained high among the blood transfusions group even after fifteen years. The three types of cancer with the highest incidence following transfusion were leukemia, stomach cancer, and liver cancer. Conclusions: Blood transfusion increases the risk of cancer in transfusion recipients. The impact of blood transfusion on cancer development varies depending on the cancer type and the time from transfusion. Further prospective studies are warranted to validate the findings and investigate the underlying mechanism. The pooled risk of cancer according to cancer types, units of transfusion, and time from transfusion Risk* (95% CI) Total < 5 yrs 5-15 yrs ≧ 15 yrs All cancer types 1.70 (1.30 - 2.10) 1.89 (1.13 - 2.65) 1.18 (0.97 - 1.40) 1.10 (1.06 - 1.14) Leukemia 2.79 (2.00 - 3.57) 4.07 (2.72 - 5.42) 1.15 (1.04 - 1.27) 0.91 (0.66 - 1.16) Non Hodgkin lymphoma 1.94 (1.49 - 2.40) 2.66 (1.82 - 3.50) 1.43 (0.89 - 1.98) 1.23 (1.00 - 1.46) Stomach 2.37 (1.70 - 3.04) 2.37 (1.70 - 3.04) 1.13 (1.03 - 1.23) 1.17 (0.91 - 1.43) Liver 2.25 (1.67 - 2.84) 2.80 (1.80 - 3.80) 1.67 (1.48 - 1.86) 2.54 (1.85 - 3.23) Colon 2.34 (1.62 - 3.05) 3.49 (1.90 - 5.08) 1.02 (0.96 - 1.08) 1.05 (0.90 - 1.20) Pancreas 1.85 (1.36 - 2.34) 2.37 (1.50 - 3.24) 1.19 (0.72 - 1.66) 1.28 (0.97 - 1.59) Rectum 1.40 (1.06 - 1.75) 1.71 (1.04 - 2.39) 0.98 (0.91 - 1.05) 1.00 (0.81 - 1.19) Lung 1.49 (1.21 - 1.77) 1.71 (1.18 - 2.23) 1.24 (1.17 - 1.30) 1.27 (1.09 - 1.45) Kidney 2.27 (1.63 - 2.90) 3.30 (1.89 - 4.17) 1.15 (1.03 - 1.27) 1.39 (0.70 - 2.08) Bladder 1.40 (1.12 - 1.68) 1.56 (1.06 - 2.06) 1.19 (1.11 - 1.27) 1.35 (0.15 - 2.54) Breast 0.96 (0.84 - 1.09) 1.06 (0.91 - 1.22) 0.95 (0.90 - 1.00) 1.12 (1.03 - 1.21) Uterus 1.02 (0.84 - 1.19) 1.13 (0.85 - 1.25) 0.81 (0.46 - 1.16) 1.00 (0.78 - 1.22) Thyroid 1.16 (0.91 - 1.41) 1.32 (0.87 - 1.77) 0.92 (0.70 - 1.14) 1.12 (0.64 - 1.78) 1-2 units ≧ 3 units All cancer types 1.53 (1.15 - 1.90) 1.93 (1.39 - 2.48) *Risk is pooled from odds ratio, hazard ratio, relative risk, and standardized incidence ratio.Abbreviations: CI=Confidence Interval Citation Format: Youjin Oh, Soowon Lee, Sebin Bok, Chan Mi Jung, Ilene Hong, Liam Chung, Jeeyeon Lee, Young Kwang Chae. Systematic review and meta-analysis of cancer incidence after blood transfusion in the general population. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4207.

Perfluoroalkyl substances exposure in firefighters: Sources and implications

Firefighters are at risk of occupational exposure to long-chain per- and poly-fluoroalkyl substances (PFASs), most notably from PFASs present in Class B aqueous film-forming foam (AFFF). Firefighters have been found to have elevated serum levels of long-chain PFASs. Due to the persistence of PFAS chemicals in the human body and their ability to bioaccumulate, firefighters experience the latent and cumulative effects of PFAS-containing AFFF exposure that occurs throughout their careers. This article summarizes the history of AFFF use by firefighters and current AFFF use practices. In addition, this paper describes PFAS levels in firefighter serum, PFAS serum removal pathways, PFAS exposure pathways, and occupational factors affecting PFAS levels in firefighters. International, national, and state agencies have concluded that PFOA, a long-chain PFAS, is potentially carcinogenic and that carcinogens have an additive effect. From the cancer types that may be associated with PFAS exposure, studies on cancer risk among firefighters have shown an elevated risk for thyroid, kidney, bladder, testicular, prostate, and colon cancer. Thus, exposure to PFAS-containing AFFF may contribute to firefighter cancer risk and warrants further research.

Association of metabolic syndrome and the risk of bladder cancer: A prospective cohort study.

BackgroundMetabolic syndrome (MetS) and its components have been shown as risk factors for several solid cancers. However, current epidemiological evidence about the relevance of MetS and bladder cancer risk was limited.MethodsWe conducted a prospective cohort study of 476,986 participants with undiagnosed bladder cancer based on the UK Biobank. MetS was defined as the presence of at least three of the five selected indicators: hypertension, central obesity, raised triglyceride, reduced HDL-cholesterol, and raised fasting plasma glucose. Bladder cancer has been identified through contact with the British Cancer Registry (median follow-up time: 6.6 years). We assessed hazard ratio (HR) and 95% confidence interval (CI) through Cox proportional hazard regression after adjusting for demographic and lifestyle factors. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method.ResultsDuring a follow-up of 3,112,566 person-years, 487 cases of bladder cancer were ascertained. MetS (HR = 1.32, 95% CI = 1.08–1.61), central obesity (HR = 1.39, 95% CI = 1.15–1.68), dyslipidemia for HDL cholesterol (HR = 1.31, 95% CI = 1.04–1.66), and hyperglycemia (HR = 1.44, 95% CI = 1.16–1.79) were associated with elevated risk of bladder cancer. Bladder cancer risk increased with the number of MetS components. In stratified analyses, MetS showed similar effects in bladder cancer independently with sex, age, cigarette and alcohol use, physical activity, and dietary factors. Higher waist circumference, BMI, fasting blood glucose, and glycosylated hemoglobin were independently associated with increased risk of bladder cancer, with no evidence against non-linearity.ConclusionMetS might be an independent risk factor for bladder cancer. Our findings highlighted the importance of individualized management of MetS components for preventing bladder cancer.

DNA Damage and Oxidative Stress of Tobacco Smoke Condensate in Human Bladder Epithelial Cells.

Smoking is a major risk factor for bladder cancer (BC), with up to 50% of BC cases being attributed to smoking. There are 70 known carcinogens in tobacco smoke; however, the principal chemicals responsible for BC remain uncertain. The aromatic amines 4-aminobiphenyl (4-ABP) and 2-naphthylamine (2-NA) are implicated in BC pathogenesis of smokers on the basis of the elevated BC risk in factory workers exposed to these chemicals. However, 4-ABP and 2-NA only occur at several nanograms per cigarette and may be insufficient to induce BC. In contrast, other genotoxicants, including acrolein, occur at 1000-fold or higher levels in tobacco smoke. There is limited data on the toxicological effects of tobacco smoke in human bladder cells. We have assessed the cytotoxicity, oxidative stress, and DNA damage of tobacco smoke condensate (TSC) in human RT4 bladder cells. TSC was fractionated by liquid-liquid extraction into an acid-neutral fraction (NF), containing polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, phenols, and aldehydes, and a basic fraction (BF) containing aromatic amines, heterocyclic aromatic amines, and N-nitroso compounds. The TSC and NF induced a time- and concentration-dependent cytotoxicity associated with oxidative stress, lipid peroxide formation, glutathione (GSH) depletion, and apurinic/apyrimidinic (AP) site formation, while the BF showed weak effects. LC/MS-based metabolomic approaches showed that TSC and NF altered GSH biosynthesis pathways and induced more than 40 GSH conjugates. GSH conjugates of several hydroquinones were among the most abundant conjugates. RT4 cell treatment with synthetic hydroquinones and cresol mixtures at levels present in tobacco smoke accounted for most of the TSC-induced cytotoxicity and the AP sites formed. GSH conjugates of acrolein, methyl vinyl ketone, and crotonaldehyde levels also increased owing to TSC-induced oxidative stress. Thus, TSC is a potent toxicant and DNA-damaging agent, inducing deleterious effects in human bladder cells at concentrations of <1% of a cigarette in cell culture media.

C-reactive protein trajectories and the risk of all cancer types: A prospective cohort study.

A single CRP measurement is insufficient to examine the association of long‐term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new‐onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific‐site cancer. Four CRP trajectories patterns were identified: low‐stable pattern (n = 43 258), moderate‐increasing pattern (n = 2591), increasing‐decreasing pattern (n = 2068) and elevated‐decreasing pattern (n = 4359). Relative to the low‐stable pattern, the moderate‐increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing‐decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing‐decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated‐decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia.

Assessing arsenic in human toenail clippings using portable X-ray fluorescence

Arsenic is a toxic metalloid which has been associated with a wide range of health effects in humans including skin abnormalities and an elevated risk of skin, bladder, kidney, and lung cancer, diabetes, and cardiovascular disease. The measurement of arsenic concentration in nail clippings is often used in population studies as an indicator of arsenic exposure. Portable X-ray fluorescence (XRF) is an emerging technique for measuring arsenic in nail clippings. In the current study, single toenail clippings from 60 Atlantic Canadian participants were assessed for arsenic using a new portable XRF approach. A mono-energetic portable XRF system using doubly curved crystal optics was used to measure each clipping for a total of 900 s. Energy spectra from each clipping were analyzed for arsenic characteristic X-rays to provide a normalized arsenic signal. The same clippings were then analyzed for arsenic concentration using a “gold standard” method of inductively coupled plasma mass spectrometry (ICP-MS). Nail clipping arsenic concentrations measured by ICP-MS ranged from 0.030 μg/g to 2.57 μg/g, with a median result of 0.14 μg/g. Portable XRF results for arsenic were compared against ICP-MS arsenic concentrations, with a linear equation of best fit determined between the two variables. A correlation coefficient of r = 0.77 was found from the 59 nail clippings returning an ICP-MS arsenic concentration above the limit of quantitation. When the comparison was limited to the 20 clippings having an XRF normalized signal at least twice as large as the associated uncertainty of measurement, the correlation coefficient was r = 0.89. With the selection of an arsenic concentration of 0.1 μg/g as a cut-off value between “exposed” and “non-exposed” individuals, the XRF method provided a test sensitivity of 76% and a specificity of 81%. The corresponding positive predictive value was 88% and the negative predictive value was 65%. The portable XRF technique used in this study shows promise as a means of assessing arsenic concentration in toenail clippings.

A population-based cohort study examining the association of documented bladder diverticulum and bladder cancer risk in urology patients.

ObjectivesStudies have shown a high risk of tumor development within a bladder diverticulum (BD). We were interested in the relationship between BD and the development of bladder cancer. Herein, we attempted to investigate whether there exists an association between documented BD and subsequent risk of bladder cancer.MethodsWe identified 10,662 hospitalized urology patients, including 2,134 documented BD patients (study cohort) and 8,528 non-BD subjects (comparison cohort) from Taiwan’s National Health Insurance database. Only urology patients were enrolled in the study to minimize selection bias. The two cohorts were frequency-matched 1:4 by age, sex and index-year. Patients with less than one year of follow-up were excluded to avoid inverting cause and effect. Risks of developing bladder cancer were estimated using the Cox proportional hazard regression model.ResultsThere was an increased bladder cancer risk in the documented BD patients. The incidence of bladder cancer in documented BD patients was 2.60-fold higher than that in the comparison group, and the overall risk-factor-adjusted hazard ratio was 2.63 (95% CI, 1.74–3.97). Moreover, stratified analysis by sex also showed that documented BD patients were at higher risk of subsequent bladder cancer than the comparison cohort. The effect of BD on the risk of bladder cancer was higher in males than in females and was more profound in patients without comorbidities than in those with comorbidities.ConclusionIn this population-based longitudinal study, urology patients with documented BD might have an elevated risk of subsequent bladder cancer. Based on the limitations of the retrospective study design, further studies are required.

1685-P: Type 1 Diabetes Mellitus and Incident Bladder Cancer: A Systematic Review and Meta-analysis

Background: A credible body of epidemiologic evidence documents elevated bladder cancer risk among patients with type 2 diabetes, but risk among those with type 1 diabetes (T1DM) has received less attention. We sought to identify and quantitatively synthesize epidemiologic data on the association between T1DM and incident bladder cancer. Methods: We searched Medline, Embase, Cochrane, and Web of Science through June 5, 2018, to identify non-redundant English language reports of original human data estimating the association between T1DM and incident bladder cancer addressing age as potential confounder. Additional citations were identified through hand searching efforts including a Google Scholar search, contacting authors, and retrieving citations in selected studies. Candidate reports were critically appraised by two independent reviewers, with conflicts resolved by consensus. Harmonized estimates of the T1DM-bladder cancer association were extracted from qualifying reports and synthesized by random effects meta-analysis. Findings: Among 7,673 reports identified in the search, 59 warranted critical full text review, and 4 described 7 non-redundant studies satisfying inclusion criteria (N=362 T1DM patients). Estimate of the overall summary odds ratio association was 1.07 (95% CI: 0.87-1.32; I2: 69.1%, p heterogeneity= 0.001; 7 studies). Gender-specific summary estimates were 1.40 (95% CI: 0.95-2.05; I2: 73.9%, p heterogeneity= 0.002; 6 studies) for females, and 0.95 (95% CI: 0.71-1.26; I2: 61.4%, p heterogeneity= 0.024; 6 studies) for males. Interpretation: Available data reveal a modest positive association between incident bladder cancer and T1DM that does not achieve statistical significance. Etiologic interpretation is precluded by indicators of heterogeneity and design limitations of contributing studies, primarily confounding by smoking and error in measurement of diabetes in referent groups. Disclosure H.B. Oskoui: None. D.D. Bogumil: None. L. Kysh: None. M. Barrett: None. K. Siegmund: None. V.K. Cortessis: None.

Evaluation of Hospital-Based Hematuria Diagnosis and Subsequent Cancer Risk Among Adults in Denmark

Data on the long-term risk of urologic and nonurologic cancer after hematuria diagnosis are sparse. Such data can improve understanding of hematuria and cancer and can provide insight into the clinical course of patients with hematuria. To assess the risk of urologic or nonurologic cancer after a hospital-based diagnosis of hematuria. This cohort study used population-based, nationwide health care databases covering all hospitals in Denmark. The data set included records of all adults (n = 134 173) with an inpatient, outpatient, or emergency department diagnosis of hematuria. The study was conducted from January 1, 1995, to December 31, 2013. Follow-up ended on December 31, 2013. Data analysis was performed from January 16, 2017, to September 18, 2018. Cumulative risk of cancer was computed, and observed cancer incidence was compared with incidence expected in the general population, using standardized incidence ratios. Of the 134 173 patients included, 52 367 (39.0%) were women, 81 806 (61.0%) were men, and the median (interquartile range) age was 59 (44-72) years. Within 3 months after hematuria diagnosis, 2647 patients (1.9%) received an invasive bladder cancer diagnosis, 1077 (0.8%) a noninvasive bladder cancer diagnosis, 569 (0.4%) a kidney cancer diagnosis, and 908 (1.1%) a prostate cancer diagnosis. The 3-month cumulative incidence (or absolute risk) of any cancer diagnosis was 4.81% (95% CI, 4.70%-4.93%), the 1-year risk was 6.65% (95% CI, 6.51%-6.78%), and the 5-year risk was 12.34% (95% CI, 12.15%-12.53%). The cumulative incidence of bladder cancer only increased from 1.20% (95% CI, 1.11%-1.30%) after 1 year to 1.36% (95% CI, 1.26%-1.46%) after 5 years of follow-up in women and from 2.93% (95% CI, 2.82%-3.05%) to 3.31% (95% CI, 3.19%-3.44%) in men. For noninvasive bladder cancer, the standardized incidence ratio in the 1 year to less than 5 years of follow-up was 5.39 (95% CI, 4.58-6.30) in patients without initial cystoscopy and was 0.16 (95% CI, 0.04-0.42) in patients with cystoscopy within 3 months after hospital-based diagnosis of hematuria. For kidney cancer, the standardized incidence ratio in the 1 year to less than 5 years of follow-up was 2.63 (95% CI, 2.15-3.18) in patients without cystoscopy and 1.20 (95% CI, 0.87-1.61) in patients with cystoscopy within 3 months after hospital-based diagnosis of hematuria. After 1 year, the risk of gynecologic and colorectal cancers was as expected or even lower, whereas the risk of hematologic malignant neoplasms remained slightly elevated. Increased risk of bladder and kidney cancers even more than 1 year after hospital-based hematuria diagnosis, as well as the slightly elevated risk of invasive bladder cancer after 5 years, may indicate that it is a marker of greater cancer risk; these findings could inform follow-up recommendations for hematuria.

Potential effect modifiers of the arsenic-bladder cancer risk relationship.

Populations exposed to arsenic in drinking water have an increased bladder cancer risk and evidence suggests that several factors may modify arsenic metabolism, influencing disease risk. We evaluated whether the association between cumulative lifetime arsenic exposure from drinking water and bladder cancer risk was modified by factors that may impact arsenic metabolism in a population-based case-control study of 1,213 cases and 1,418 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between cumulative arsenic intake and bladder cancer stratified by age, sex, smoking status, body mass index (BMI), alcohol consumption and folate intake. P-values for interaction were computed using a likelihood ratio test. We observed no statistically significant multiplicative interactions although some variations in associations were notable across risk factors, particularly for smoking and BMI. Among former smokers and current smokers, those with the highest cumulative arsenic intake had elevated risks of bladder cancer (OR = 1.4, 95% CI: 0.96-2.0 and OR = 1.6, 95% CI: 0.91-3.0, respectively; while the OR among never smokers was 1.1, 95% CI: 0.6-1.9, p-interaction = 0.49). Among those classified as normal or overweight based on usual adult BMI, the highest level of cumulative arsenic intake was associated with elevated risks of bladder cancer (OR = 1.3, 95% CI: 0.89-2.0 and OR = 1.6, 95% CI: 1.1-2.4, respectively), while risk was not elevated among those who were obese (OR = 0.9, 95% CI: 0.4-1.8) (p-interaction = 0.14). Our study provides some limited evidence of modifying roles of age, sex, smoking, BMI, folate and alcohol on arsenic-related bladder cancer risk that requires confirmation in other, larger studies.

Association between lncRNA H19 (rs217727, rs2735971 and rs3024270) polymorphisms and the risk of bladder cancer in Chinese population.

The Long non-coding RNA (lncRNA) H19 is involved in carcinogenesis, progression, and metastasis. However, the association between genetic variants in H19 and bladder cancer susceptibility has not been reported. This case-control study assessed the association between H19 genetic variants and susceptibility to bladder cancer in a Chinese Han population. In this study, 200 patients with bladder cancer and 200 healthy controls were surveyed and compared for frequencies of the genotypes of the H19 gene. Logistic regression analysis and the chi-square test were employed as statistical methods. Odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were calculated to estimate the strength of association between H19 polymorphisms and risk of bladder cancer. We analyzed the frequency of three lncRNA H19 SNPs in 200 bladder cancer patients and 200 healthy controls. Carriers of variant rs217727 heterozygous genotype showed increased bladder cancer risk (P=0.008). Further stratified analyses revealed that the association between bladder cancer risk and variant genotypes of rs217727 was more profound in smokers. Furthermore, decreased risk of invasive bladder cancer was found in carrying rs3024270 CC patients. Our results provided the evidence that rs217727 in H19 was associated with elevated risk of bladder cancer, which may be a potential biomarker for predicting bladder cancer susceptibility. Furthermore, invasive bladder cancer in carrying rs3024270 CC genotype maybe have a good prognosis.