Relative Risk Of Bladder Cancer Research Articles

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<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 risk of bladder cancer in young adult men with hyperlipidemia: A population-based cohort study.

A high-cholesterol diet increases the risk of bladder cancer. The purpose of this nationwide longitudinal population-based retrospective cohort study is to investigate whether hyperlipidemia is a risk factor for bladder cancer.Data from Taiwan National Health Insurance Database were analyzed. The primary study end point was the occurrence of newly diagnosed bladder cancer. The relative risk of bladder cancer in a hyperlipidemia cohort was compared with that in an age- and gender-matched non-hyperlipidemia cohort by using the Cox proportional hazards regression model. Cox regression analyses were further adjusted by the propensity score.Our data revealed that the hyperlipidemia cohort (n = 33,555) had a significantly higher subsequent risk of bladder cancer than did the non-hyperlipidemia cohort (n = 33,555) (adjusted hazard ratio [HR] = 1.37, P = .005) after propensity score adjustment. Subgroup analyses revealed that men in the hyperlipidemia cohort had a significantly higher subsequent risk of bladder cancer than did those in the non-hyperlipidemia cohort (adjusted HR = 1.36, P = .040). However, the risk of bladder cancer was not significantly different between women in the hyperlipidemia cohort and those in the non-hyperlipidemia cohort. Subgroup analyses further revealed that the risk of bladder cancer was significantly higher in men aged 20 to 39 years in the hyperlipidemia cohort than in those in the non-hyperlipidemia cohort (adjusted HR = 5.45, P = .029).In conclusion, hyperlipidemia is a risk factor for bladder cancer in young adult men.

Bayesian benchmark dose analysis for inorganic arsenic in drinking water associated with bladder and lung cancer using epidemiological data

Abundant epidemiological evidence has shown that there is a strong causal relationship between long-term exposure to inorganic arsenic (iAs) through drinking water and a few types of cancer (e.g., lung and bladder cancer). Traditionally, a linear low-dose extrapolation assumption was applied in risk assessment for iAs which resulted in a relatively conservative cancer risk estimate. Growing biological evidence suggests that the mode of action of iAs-induced cancer follows a threshold process (e.g., sufficient concentration of trivalent arsenic is required to disrupt normal cellular function). In this study, we applied the benchmark dose (BMD) methodology to model the relationship between the relative risk of bladder and lung cancer and the iAs concentration in drinking water using the high-quality epidemiological data reported in recently published papers, with a special focus on the low exposure range (i.e., <150 μg/L). Because of its biological plausibility and statistical flexibility, the Hill model has been chosen to model the data under a Bayesian framework. A Bayesian hierarchal model together with a bootstrap method for exposure estimation were applied to quantify uncertainty from various sources, including the within-study, between-study, and exposure uncertainties. Dose-response assessment results obtained from a number of alternative model structures and methods consistently demonstrate a threshold type dose-response curve with a threshold in the range between 40–60 μg/L of iAs concentration in drinking water. The BMD for iAs in drinking water associated with 0.1 % increase in relative risk of bladder cancer is 42.2 μg/L (BMDL 39.2 μg/L); for 0.05 % increase, the BMD is 41.6 μg/L (BMDL 38.6 μg/L). For lung cancer, the two counterpart BMD estimates are 57.0 μg/L (BMDL 43.6 μg/L) and 55.7 μg/L (BMDL 42.5 μg/L) for 0.1 % and 0.05 % increase, respectively. These analyses provide additional statistical support for a non-linear dose response for cancer risk from inorganic arsenic which may have important policy implications.

Differential DNA methylation in blood as a mediator of the association between cigarette smoking and bladder cancer risk among postmenopausal women

ABSTRACTSmoking accounts for approximately 52% of bladder cancer incidence among postmenopausal women, but the underlying mechanism is poorly understood. Our study investigates whether changes in DNA methylation, as measured in blood, mediate the impact of smoking on bladder cancer risk among postmenopausal women. We conducted analyses among 206 cases and 251 controls that were current or never smokers at baseline from a previous case-control study of bladder cancer and genome-wide DNA methylation nested within the Women’s Health Initiative. Separate mediation analyses were conducted for three CpG sites demonstrating robust associations with smoking in prior methylome-wide association studies: cg05575921 (AhRR), cg03636183 (F2RL3), and cg19859270 (GPR15). We estimated causal effects using the regression-based, four-way decomposition approach, which addresses the interaction between smoking and each CpG site. The overall proportion of the excess relative risk mediated by cg05575921 was 92% (p-value = 0.004) and by cg19859270 was 79% (p-value = 0.02). The largest component of the excess relative risk of bladder cancer due to 30 pack-years of smoking history in current smokers was the mediated interaction for both cg05575921 (72%, p = 0.02) and cg19859270 (72%, p-value = 0.04), where the mediated interaction is the effect of smoking on bladder cancer that both acts through differential methylation and depends on smoking history. There was little evidence that smoking was mediated through cg03636183. Our results suggest that differential methylation of cg05575921 and cg19859270 mediate the effects of smoking on bladder cancer, potentially revealing downstream effects of smoking relevant for carcinogenesis.

Parity and bladder cancer risk: a dose-response meta-analysis

BackgroundMultiple studies have reported evidence of an inverse association between parity and bladder cancer risk. However, a comprehensive and quantitative assessment of this association has never been conducted. We conducted this study to clarify this issue.MethodsSystematic search of PubMed and Embase was performed to identify all the studies. Studies were selected based on strict screening with inclusion and exclusion criteria. Summary relative risks (RR) with 95% confidence intervals (CI) were calculated by using a fixed-effect model, and the generalized least squares trend estimation was employed to compute study-specific RR and 95% CI per live birth increase. Heterogeneity and publication bias were also evaluated.ResultsTwelve studies (6,214 cases and 2,693,350 non-cases) were eligible in this meta-analysis. The pooled RR of bladder cancer for parous versus nulliparous women was 0.76 (95% CI: 0.70–0.82). Results were similar in the studies that adjusted for BMI(RR = 0.66; 95% CI: 0.53–0.81), cigarette smoking (RR = 0.67; 95% CI: 0.57–0.79), and age (RR = 0.77; 95% CI: 0.71–0.84). The dose-response meta-analysis showed a lower bladder cancer risk (RR = 0.95; 95% CI: 0.92–0.98) for each live birth increase in parous women. No evidence of publication bias or significant heterogeneity was detected in the above-mentioned analyses.ConclusionsThe finding from current meta-analysis suggest that parity may be related to decreased risk of bladder cancer.

In Reply

The sensitivity analyses suggested in the Letter to the Editor by de Vries et al. was performed, but no material change in relative risk for bladder cancer was found. This is not surprising given the limited contribution of the studies excluded in the sensitivity analyses.

Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies

BackgroundIncreasing evidence suggests that a history of diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. We performed a systematic review with meta-analysis to explore this relationship.MethodsWe identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 29 February 2012, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model.ResultsA total of 36 studies (9 case–control studies, 19 cohort studies and 8 cohort studies of patients with diabetes) fulfilled the inclusion criteria. Analysis of all studies showed that DM was associated with an increased risk of bladder cancer (the summary RR = 1.35, 95% CI 1.17–1.56, p < 0.001, I2 = 94.7%). In analysis stratified by study design, diabetes was positively associated with risk of bladder cancer in case–control studies (RR = 1.45, 95% CI 1.13-1.86, p = 0.005, I2 = 63.8%) and cohort studies (RR = 1.35, 95% CI 1.12-1.62, p < 0.001, I2 = 94.3%), but not in cohort studies of diabetic patients (RR = 1.25, 95% CI 0.86–1.81, p < 0.001, I2 = 97.4%). The RRs of bladder cancer were 1.38 (1.08-1.78) for men and 1.38 (0.90-2.10) for women with diabetes, respectively. Noteworthy, the relative risk of bladder cancer was negatively correlated with the duration of DM, with the higher risk of bladder cancer found among patients diagnosed within less than 5 years.ConclusionsThese findings support the hypothesis that men with diabetes have a modestly increased risk of bladder cancer, while women with diabetes were not the case.

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

BackgroundIncreasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models.ResultsA total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I2 = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I2 = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14).ConclusionThese findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.

Cancer Risk for Patients Using Thiazolidinediones for Type 2 Diabetes: A Meta-Analysis

To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies. A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR). Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91-1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07-1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95-1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90-0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48-0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers. Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.

Abstract A76: Diabetes and risk of bladder cancer among postmenopausal women in the Iowa Women's Health Study

Abstract Several epidemiological studies investigated diabetes as a risk factor for bladder cancer. A meta-analysis of 16 studies reported a relative risk of bladder cancer of 1.24 in adults with diabetes. However, many of those studies did not adjust for potential confounders. The Iowa Women's Health Study (IWHS) was included in that meta-analysis, but during the follow-up (1986–1998), there were only 112 incident bladder cancer cases, 12 of which had diabetes reported at baseline. We updated the analysis of the association between diabetes and bladder cancer occurrence (n=265) in the IWHS with follow-up through 2008. Our goal was to more accurately estimate the risk of bladder cancer in relation to diabetes at baseline and during follow-up: 1987, 1989, 1992, and 1997. We also studied whether the association varied by the time between the self-reported onset of diabetes and bladder cancer (diabetes duration), and by obesity measures – body mass index (BMI) and waist-to-hip ratio (WHR). We used Cox proportional hazards regression to estimate hazard ratio (HR) of bladder cancer and 95% confidence interval (CI) for baseline diabetes, and extended Cox regression to conduct a time-dependent analysis for diabetes during follow-up. To examine an association of diabetes duration with bladder cancer incidence, we conducted a nested case-control analysis. For each case, 4 controls were randomly chosen among all IWHS participants who were alive and free of cancer on the date of cancer diagnosis. Controls were matched to cases by year of birth and were assigned an index date, equivalent to the diagnosis date of the matched case. Conditional logistic regression was used to estimate the odds ratio (OR) of bladder cancer. The cohort for the person-time analysis included 37,459 initially cancer-free post-menopausal women (mean age at baseline was 61.7 y, 99.9% were white). In the multivariate analysis diabetics at baseline had an HR=1.51 (95% CI, 0.91;2.50) compared to non-diabetics. The weaker association in the present than in an earlier analysis (HR=2.5, 95% CI, 1.3;4.5) could be due to a prolonged follow-up and non-differential misclassification of diabetes status and/or survival bias. In the time-dependent analysis accounting for incident diabetes after the baseline, the HR for bladder cancer was 1.77 (95% CI, 1.24;2.51) for yes versus no diabetes. The association did not markedly change after excluding women with an onset of diabetes before 30 years of age or with diabetes duration &amp;lt;2 y. There was no interaction between diabetes and smoking. After stratification by BMI, HRs of bladder cancer for diabetics versus non-diabetics were 1.29 (95%CI, 0.60;2.79), 1.52 (95%CI, 0.83;2.79), and 2.60 (95%CI, 1.46;4.61) for BMI&amp;lt;25, 25–30 and &amp;gt;30 kg/m2, respectively. Associations between diabetes and bladder cancer were stronger for higher WHR. Finally, in the nested case-control analysis, the HRs of bladder cancer for patients with diabetes duration &amp;lt;5, 5–10, and &amp;gt;10 y were 1.65 (95%CI, 0.76; 3.60), 2.18 (95%CI, 0.85;5.60), 3.37 (95%CI, 0.88;12.87) (p-trend=0.03). In summary, we have confirmed a statistically significant positive association between diabetes and bladder cancer risk among white post-menopausal women. It may be explained by the mitogenic properties of insulin and/or increased likelihood of urinary tract infections in diabetics. The association was stronger with longer diabetes duration and with increasing adiposity. The latter association may reflect more severe diabetes among obese individuals and its larger influence on bladder carcinogenesis. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A76.

Bladder Cancer Working Group Report

EPIDEMIOLOGY OF BLADDER CANCER: Bladder cancer is the 7th most common cancer in men and the 17th most common in women in the world. The incidence of bladder cancer varies considerably among countries, with the highest incidence rates seen in Western countries and the lowest rates in Asian countries. In recent years, the mortality rate due to bladder cancer has been stable or decreased gradually. LIFESTYLE AND UROTHELIAL CARCINOMA: Occupational risks, environmental risks, dietary habits and cigarette smoking are lifestyle factors known to influence the development of urothelial carcinoma. Although the relative risk of bladder cancer associated with occupations is small, the public health impact may be significant. The Western pattern of diet is associated with a significant increase in the risk of bladder cancer. It has been found that smoking accounts for more than 50% of bladder cancers in men and 30% in women. Urological patients' awareness of smoking as a risk factor for bladder cancer is lower than their awareness regarding other smoking-related disease entities. Counseling patients regarding the risk of tobacco is a role for urologists. GENETIC SUSCEPTIBILITY TO UROTHELIAL CARCINOMA: Recent single-nucleotide polymorphism genetic studies in relation to bladder carcinogenesis have revealed several associated genetic polymorphisms of detoxification or DNA repair genes, such as NAT2, GST and OGG1. That information is important in relation to environmental risk factors and ethnic differences and will help predict the prognosis of patients with bladder cancer. Further studies are needed to confirm potential gene-gene and gene-environmental interactions leading to bladder carcinogenesis.

Radiation Therapy for Prostate Cancer Increases Subsequent Risk of Bladder and Rectal Cancer: A Population Based Cohort Study

Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer. We estimated the risk of secondary bladder cancer and rectal cancer after prostate radiotherapy using a contemporary population based cohort. We identified 243,082 men in the Surveillance, Epidemiology and End Results database who underwent radical prostatectomy or radiotherapy for prostate cancer between 1988 and 2003. We estimated the incidence rate, standardized incidence ratio and age adjusted incidence rate ratio of subsequent bladder cancer and rectal cancer associated with radical prostatectomy, external beam radiotherapy, brachytherapy, and a combination of external beam radiotherapy and brachytherapy. The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively. Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively. The relative risk of rectal cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.26, 1.08 and 1.21, respectively. The standardized incidence ratio for rectal cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.91, 0.99, 0.68 and 0.86, respectively. Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population. The risk of rectal cancer is increased in patients who receive external beam radiotherapy compared to radical prostatectomy. Patients should be counseled appropriately regarding these risks.

Body Mass Index, Physical Activity, and Bladder Cancer in a Large Prospective Study

Increased body size and lack of physical activity are associated with increased risk of several cancers, but the relations of body mass index (BMI) and physical activity to bladder cancer are poorly understood. We investigated the associations between BMI, physical activity, and bladder cancer in the NIH-AARP Diet and Health Study, a prospective cohort of 471,760 U.S. men and women, followed from 1995 to 2003. During 3,404,642 person-years of follow-up, we documented 1,719 incident cases of bladder cancer. Compared with normal weight, obesity was associated with an up to 28% increased risk for bladder cancer. The multivariate relative risks of bladder cancer for BMI values of 18.5 to 24.9 (reference), 25.0 to 29.9, 30.0 to 34.9, and >or=35 kg/m2 were 1.0, 1.15, 1.22, and 1.28 (95% confidence interval, 1.02-1.61; P trend = 0.028). The association between BMI and bladder cancer was consistent among subgroups defined by gender, education, smoking status, and other potential effect modifiers. In contrast, physical activity showed no statistically significant relation with bladder cancer. After multivariate adjustment, including BMI, the relative risks of bladder cancer for increasing frequency of physical activity [0 (reference), <1, 1-2, 3-4, and >or=5 times a week] were 1.0, 0.85, 0.89, 0.91, and 0.87 (95% confidence interval, 0.74-1.02; P trend = 0.358), respectively. In conclusion, these findings provide support for a modest adverse effect of adiposity on risk for bladder cancer. In contrast, our results do not suggest a relation between physical activity and bladder cancer.

Bladder Cancer Risk Following Primary and Adjuvant External Beam Radiation for Prostate Cancer

Purpose Increased rates of secondary bladder malignancies have been reported after external beam radiation therapy (EBRT) for gynecological malignancies with relative risks of 2 to 4. This study was designed to determine if there was an increase in bladder cancer after EBRT for prostate cancer. Materials and Methods We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder cancer were identified. Comparative incidence rates were obtained from the national Surveillance, Epidemiology and End Results database. Subset analysis included patients treated with adjuvant radiation and those residing locally. Medical histories of patients with bladder cancer were reviewed. Results A total of 1,743 patients received EBRT for prostate cancer at our institution. In more than 12,353 man-years of followup no increase in bladder cancer risk was encountered. Subset analysis of men who received adjuvant radiation demonstrated that the relative risk of bladder cancer was increased but was not statistically significant. When the analysis was restricted to patients residing in the local area, the number of patients in whom subsequent bladder cancer developed was similar to Surveillance, Epidemiology and End Results rates. However, in the adjuvant radiation subset there was a statistically significant increase in subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT often present with low grade disease but many have recurrence and progression. Conclusions This retrospective review suggests there is not evidence of increased risk of bladder cancer after radiation therapy, assuming unbiased followup and complete ascertainment of cases. The natural history of bladder cancer in this population does not seem to be altered by a history of radiation.

A meta-analysis on the association between bladder cancer and occupation

To date, many epidemiological studies have been conducted to examine the association between occupation and bladder cancer incidence. However, results from these studies often have been inconsistent, and significant associations have rarely been found, possibly owing to the lack of adequate statistical power in these studies. This meta-analysis summarizes the relevant literature regarding occupation and bladder cancer incidence to increase the statistical power to detect associations. The Medline and Embase databases were searched to retrieve epidemiological studies published up until May 2008. Individual risk estimates for subjects with an employment history in the occupation of interest were extracted from each included publication. For each occupation, a summary relative risk (SRR) was calculated by means of a random effects model. Significantly increased risks with an SRR greater than 1.20 were identified for miners [SRR=1.31, 95% confidence interval (CI) 1.09-1.57], bus drivers (SRR=1.29, 95% CI 1.08-1.53), rubber workers (SRR=1.29, 95% CI 1.06-1.58), motor mechanics (SRR=1.27, 95% CI 1.10-1.46), leather workers (SRR=1.27, 95% CI 1.07-1.49), blacksmiths (SRR=1.27, 95% CI 1.02-1.58), machine setters (SRR=1.24, 95% CI 1.09-1.42), hairdressers (SRR=1.23, 95% CI 1.11-1.37) and mechanics (SRR=1.21, 95% CI 1.12-1.31). In conclusion, the studies reviewed provide consistent support for a small but significant increased risk of bladder cancer among workers in these nine occupations. Although the relative risk of bladder cancer associated with these occupations is small, the public health impact may be significant, considering the substantial number of people who were and are employed in these occupations.

Coffee and alcohol consumption and bladder cancer

Epidemiological studies on coffee, alcohol and bladder cancer risk published up to 2007 were reviewed. Coffee drinkers have a moderately higher relative risk of bladder cancer compared to non-drinkers. The association may partly be due to residual confounding by smoking or dietary factors, but the interpretation remains open to discussion, although the absence of dose and duration-risk relations weighs against the presence of a causal association. Most studies of alcohol and bladder cancer found no association, with some studies finding a direct and other an inverse one. This again may be due to differential confounding effect of tobacco smoking--the major risk factor for bladder cancer--in various populations. Thus, epidemiological findings on the relation between alcohol drinking and bladder cancer exclude any meaningful association.

Bladder Cancer in Perfluorooctanesulfonyl Fluoride Manufacturing Workers

To determine whether bladder cancer is associated with exposure to perfluorooctane sulfonate (PFOS) in an occupational cohort. Incidence of bladder cancer was ascertained by postal questionnaire to all living current and former employees of the facility (N = 1895) and death certificates for deceased workers (N = 188). Exposure to PFOS was estimated with work history records and weighted with biological monitoring data. Standardized incidence ratios (SIRs) were estimated using U.S. population-based rates as a reference. Bladder cancer risk within the cohort was evaluated using Poisson regression by cumulative PFOS exposure. Questionnaires were returned by 1,400 of the 1895 cohort members presumed alive. Eleven cases of primary bladder cancer were identified from the surveys (n = 6) and death certificates (n = 5). The SIRs were 1.28 (95% confidence interval [CI] = 0.64-2.29) for the entire cohort and 1.74 (95% CI = 0.64-3.79) for those ever working in a high exposed job. Compared with employees in the lowest cumulative exposure category, the relative risk of bladder cancer was 0.83 (95% CI = 0.15-4.65), 1.92 (95% CI = 0.30-12.06), and 1.52 (95% CI = 0.21-10.99). The results offer little support for an association between bladder cancer and PFOS exposure, but the limited size of the population prohibits a conclusive exposure response analysis.

A Prospective Cohort Study of Bladder Cancer Risk in Relation to Active Cigarette Smoking and Household Exposure to Secondhand Cigarette Smoke

Active cigarette smoking is a major risk factor for bladder cancer. Secondhand exposure to cigarette smoke may also contribute to bladder carcinogenesis. The authors conducted a prospective cohort study to examine the influence of both active smoking and household exposure to secondhand smoke (SHS) on subsequent bladder cancer risk. The study population included persons from two cohorts established from private censuses conducted in Washington County, Maryland, in 1963 (n = 45,749; 93 cases) and 1975 (n = 48,172; 172 cases). Poisson regression models were fitted to estimate the relative risk of bladder cancer associated with active and passive smoke exposure in the two cohorts (referent category: never smokers who did not live with any smokers). Current smokers had an elevated risk of bladder cancer in both the 1963 cohort (relative risk (RR) = 2.7, 95% confidence limits (CL): 1.6, 4.7) and the 1975 cohort (RR = 2.6, 95% CL: 1.7, 3.9) after adjustment for age, education, and marital status. Among nonsmoking women, current household SHS exposure was associated with bladder cancer risk in the 1963 cohort (RR = 2.3, 95% CL: 1.0, 5.4) but not in the 1975 cohort (RR = 0.9, 95% CL: 0.4, 2.3). This study further solidifies the evidence that active smoking is causally associated with bladder cancer. Additional studies are needed to determine whether passive smoking is a risk factor for bladder cancer.

NAT2 slow acetylation and bladder cancer in workers exposed to benzidine: Carreón T, Ruder AM, Schulte PA, Hayes RB, Rothman N, Waters M, Grant DJ, Boissy R, Bell DA, Kadlubar FF, Hemstreet GP III, Yin S, LeMasters GK, Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, OH

This study expands a previous study of NAT2 polymorphisms and bladder cancer in male subjects occupationally exposed only to benzidine. The combined analysis of 68 cases and 107 controls from a cohort of production workers in China exposed to benzidine included 30 new cases and 67 controls not previously studied. NAT2 enzymatic activity phenotype was characterized by measuring urinary caffeine metabolite ratios. PCR-based methods identified genotypes for NAT2 , NAT1 and GSTM1 . NAT2 phenotype and genotype data were consistent. A protective association was observed for the slow NAT2 genotype (bladder cancer OR = 0.3; 95% CI = 0.1 = 1.0) after adjustment for cumulative benzidine exposure and lifetime smoking. Individuals carrying NAT1wt/*10 and NAT1*10/*10 showed higher relative risks of bladder cancer (OR = 2.8, 95% CI = 0.8–10.1 and OR = 2.2, 95% CI = 0.6–8.3, respectively). No association was found between GSTM1 null and bladder cancer. A metaanalysis risk estimate of case-control studies of NAT2 acetylation and bladder cancer in Asian populations without occupational arylamine exposures showed an increased risk for slow acetylators. The lower limit of the confidence interval (OR = 1.4; 95% CI = 1.0–2.0) approximated the upper confidence interval for the estimate obtained in our analysis. These results support the earlier finding of a protective association between slow acetylation and bladder cancer in benzidine-exposed workers, in contrast to its established link as a risk factor for bladder cancer in people exposed to 2-naphthylamine and 4-aminobiphenyl. Study findings suggest the existence of key differences in the metabolism of mono- and diarylamines.

Municipal distribution of bladder cancer mortality in Spain: Possible role of mining and industry

BackgroundSpain shows the highest bladder cancer incidence rates in men among European countries. The most important risk factors are tobacco smoking and occupational exposure to a range of different chemical substances, such as aromatic amines.MethodsThis paper describes the municipal distribution of bladder cancer mortality and attempts to "adjust" this spatial pattern for the prevalence of smokers, using the autoregressive spatial model proposed by Besag, York and Molliè, with relative risk of lung cancer mortality as a surrogate.ResultsIt has been possible to compile and ascertain the posterior distribution of relative risk for bladder cancer adjusted for lung cancer mortality, on the basis of a single Bayesian spatial model covering all of Spain's 8077 towns. Maps were plotted depicting smoothed relative risk (RR) estimates, and the distribution of the posterior probability of RR>1 by sex. Towns that registered the highest relative risks for both sexes were mostly located in the Provinces of Cadiz, Seville, Huelva, Barcelona and Almería. The highest-risk area in Barcelona Province corresponded to very specific municipal areas in the Bages district, e.g., Suría, Sallent, Balsareny, Manresa and Cardona.ConclusionMining/industrial pollution and the risk entailed in certain occupational exposures could in part be dictating the pattern of municipal bladder cancer mortality in Spain. Population exposure to arsenic is a matter that calls for attention. It would be of great interest if the relationship between the chemical quality of drinking water and the frequency of bladder cancer could be studied.