Significant Bladder Cancer Risk Research Articles

The Long-Term Impact of 5-alpha Reductase Inhibitors on the Development of Bladder Cancer and the Need for Radical Cystectomy: A Nationwide Observational Study.

To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC. From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed. Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration. Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression.

PD29-06 ASSOCIATION BETWEEN AGENT ORANGE EXPOSURE AND RISK OF BLADDER CANCER: A NATIONWIDE COHORT STUDY

You have accessJournal of UrologyCME1 Apr 2023PD29-06 ASSOCIATION BETWEEN AGENT ORANGE EXPOSURE AND RISK OF BLADDER CANCER: A NATIONWIDE COHORT STUDY Stephen Williams, Jessica Janes, Lauren Howard, Amanda DeHoedt, Jacques Baillargeon, Yong-Fang Kuo, Douglas Tyler, Martha Terris, and Stephen Freedland Stephen WilliamsStephen Williams More articles by this author , Jessica JanesJessica Janes More articles by this author , Lauren HowardLauren Howard More articles by this author , Amanda DeHoedtAmanda DeHoedt More articles by this author , Jacques BaillargeonJacques Baillargeon More articles by this author , Yong-Fang KuoYong-Fang Kuo More articles by this author , Douglas TylerDouglas Tyler More articles by this author , Martha TerrisMartha Terris More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To date, limited data exist regarding the link between Agent Orange (AO) and bladder cancer (BC) risk and the Institute of Medicine (IOM) concluded the interplay between AO exposure and BC outcomes is an area of needed research. We examined the relationship between AO exposure and BC risk in Vietnam Veterans. METHODS: We performed a nationwide Veterans Affairs (VA) retrospective cohort study to determine BC risk according to AO exposure. A total of 19,323,708 Vietnam Veterans enrolled in the VA from 2000-2019 were identified. Due to limited numbers of female patients exposed to agent orange, the study was limited to males. AO exposed patients were matched on a 1:3 basis by age, gender, race, military branch, and year of service entry to non-AO exposed patients. Risk of BC was measured by incidence and aggressiveness by muscle-invasion status using natural language processing. Multivariable cox proportional-hazards regression was used to test the association between AO and BC incidence with time zero being entry into the VA system. Multivariable logistic regression was used to test the association between AO and BC aggressiveness among men with BC. RESULTS: After inclusion and exclusion criteria, there were 629,907 (25.0%) patients with AO exposure and 1,888,019 (75.0%) matched patients without AO exposure. AO exposure was associated with significant increased risk of BC, though effect was very slight (Hazard ratio (HR) 1.03; 95% Confidence Interval (CI) 1.01-1.05). When stratified by median age at VA entry, AO was not associated with significant BC risk among older patients but was associated with increased BC risk among younger patients (HR 1.07; 95% CI 1.04-1.10). Among veterans diagnosed with BC (n=50,781), AO was associated with lower risk of muscle-invasive BC (Odds ratio (OR) 0.91, 95% CI, 0.85-0.98). CONCLUSIONS: In the largest case matched study among Vietnam Veterans to date, there was an increased risk of BC, but not BC aggressiveness among AO exposed Veterans, though the increased risk was small. These findings suggest a link between AO exposure and risk of BC. Source of Funding: This study was conducted with the support of a Department of Defense Peer Reviewed Cancer Research Program (PRCRP) Career Development Award (W81XWH1710576) (SBW). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense or Veterans Affairs © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e826 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephen Williams More articles by this author Jessica Janes More articles by this author Lauren Howard More articles by this author Amanda DeHoedt More articles by this author Jacques Baillargeon More articles by this author Yong-Fang Kuo More articles by this author Douglas Tyler More articles by this author Martha Terris More articles by this author Stephen Freedland More articles by this author Expand All Advertisement PDF downloadLoading ...

Vitamin D3 Intake Dose and Common Cancer: A Population-Based Case Control Study in a Chinese Population

Objectives: Epidemiological studies suggest that vitamin D status is associated inversely with risk of common cancers in western populations. This study aimed to investigate whether vitamin D is associated with risk of common cancers in Chinese population.Methods: A population-based retrospective case-control study was conducted analyzing data retrieved from the Catastrophic Illness Patient Databases (CIPD) and longitudinal health insurance database (LHID) from January 1, 2010 to December 31, 2011and January 1, 2000 to December 31, 2011, respectively. Cases were identified as subjects diagnosed with site-specific cancers (International Classification of Diseases, Ninth Revision,) and frequency matched to select controls. Use of vitamin D3 was compared between two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to vitamin D3 by logistic regression.Results: There were 1.21% (1961/161806) patients in cases and 0.67 % (1092/161806) patients in controls identified were vitamin D3 users. Overall risk of cancers associated with vitamin D3 users was 1.67 (95% CI:1.55 -1.81). Among these, the risk of kidney cancer and bladder cancer associated with intakes of vitamin D3 were significant (OR 2.59; 95% CI 1.81-3.70; OR 4.97; 95% CI 4.40-5.60) in an adjusted model. In further stratification analysis, we found a statistically significant risk of bladder cancer associated with high intake of vitamin D3. Except this, no statistically significant risk of other site-specific cancers associated with high intake of vitamin D3.Conclusion: Except bladder cancer in stratification analysis, we observed no statistically significant association between high intake of vitamin D3 and other site-specific cancers.

Interleukin-12 and Interleukin-6 Gene Polymorphisms and Risk of Bladder Cancer in the Iranian Population

Interleukin-12 (IL-12) as an antitumor and interleukin-6 (IL-6) as an inflammatory cytokine, are immunomodulatory products that play important roles in responses in cancers and inflammation. We tested the association between two polymorphisms of IL-12(1188A>C; rs3212227) and IL-6 (-174 C>G) and the risk of bladder cancer in 261 patients and 251 healthy individuals. We also investigated the possible association of these SNPs in patients with high-risk jobs and smoking habits with the incidence of bladder cancer. The genotype distributions of IL-6 (-174 C/G) genotype were similar between the cases and the control groups; however, among patients with smoking habits, the association between IL-6 gene polymorphism and incidence of bladder cancer was significant. After a control adjustment for age and sex, the following results were recorded: CC genotype (OR= 2.11, 95%CI=1.56-2.87, p=0.007), GC genotype (OR=2.18, 95%CI=1.16-4.12, p=0.014) and GC+ CC (OR=2.6, 95%CI=1.43-4.47, p=0.011). A significant risk of bladder cancer was observed for the heterozygous genotype (AC) of IL-12 (OR=1.47, 95%CI=1.01-2.14, p=0.045) in all cases, and among smokers (AC) (OR=3.13, 95%CI=1.82-5.37, p=0.00014), combined AC+CC (OR=3.05, 95%CI=1.8-5.18, p=0.000015). Moreover among high risk job patients, there was more than a 3-fold increased risk of cancer in the carriers of IL-12 beta heterozygous (OR=3.7, 95%CI=2.04-6.57, p=0.000056) and combined AC+CC(OR=3.29, 95%CI=1.58-5.86, p=0.00002) genotypes as compared with the AA genotype with low-risk jobs. As a conclusion, this study suggests that IL-12(3'UTR A>C) and IL-6 (-174 C>G) genotypes are significantly associated with an increased risk of bladder cancer in the Iranian population with smoking habits and/or performing high-risk jobs.

Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case-control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16-3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05-1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4-6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03-2.53) compared with those with 0-3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03-2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer.

XRCC1 Genetic Polymorphisms and Bladder Cancer Susceptibility: A Meta-analysis

To examine the association between three x-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms (Arg(194)Trp, Arg(280)His, and Arg(399)Gln) and bladder cancer susceptibility. A comprehensive search was conducted to identify all case-control studies of XRCC1 polymorphisms and bladder cancer risk. Statistical analysis was performed with the software program Review Manage, version 4.2. A total of 10 eligible reports, including 3749 cases and 3947 controls, were identified. For Arg(194)Trp (six studies, 3091 cases, 3219 controls), no evidence indicated that individuals carrying the variant genotypes (Trp/Trp + Arg/Trp), relative to those carrying the wild homozygote Arg/Arg genotype, had a decreased risk of bladder cancer (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.77 to 1.05; P = 0.17). For Arg(280)His (three studies, 2547 cases, 1784 controls), individuals with His/His+Arg/His genotypes had no significant risk of bladder cancer, compared with those with the Arg/Arg genotype (OR 0.99, 95% CI 0.55 to 1.77; P = 0.97). For Arg(399)Gln (10 studies, 3729 cases, 3927 controls), the Gln/Gln genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype (OR 0.95, 95% CI 0.82 to 1.10; P = 0.48). Similarly, no associations were found in the recessive and dominant modeling (Gln/Gln versus Arg/Gln+Arg/Arg: OR 0.92, 95% CI 0.80 to 1.05; P = 0.23; Arg/Gln+Gln/Gln versus Arg/Arg: OR 1.04, 95% CI 0.95 to 1.14; P = 0.36). No association was found between the polymorphisms in XRCC1 (Arg(194)Trp, Arg(280)His, Arg(399)Gln) and bladder cancer susceptibility.

Lifestyle issues and genitourinary tumours.

A variety of lifestyle factors, including physical activity, artificial sweeteners, alcohol consumption and smoking, have been reported to contribute to the risk of developing urological malignancies. A great number of epidemiological studies suggest that sports and physical activity may have a preventive influence on genitourinary tumours, especially on the incidence of prostate cancer. Smoking appears to be the most relevant lifestyle factor significantly increasing both incidence and mortality from bladder cancer. Furthermore, there is evidence implicating an association between tobacco use and kidney cancer. In contrast, prostate and testicular cancers are unlikely to be linked to tobacco use. As far as alcohol is concerned, most studies indicate that neither amount nor type of alcohol seems to be clearly associated with a risk of developing urological malignancies. However, some more recent cohort studies suggest a moderately increased risk for prostate and bladder cancer for specific types of alcohol. On the other hand, there is evidence that moderate alcohol consumption may even protect women from developing renal cancer. Since the introduction of artificial sweeteners, reports of potential cancer risks have circulated periodically through the mass media. The wide distribution of these agents and the fact that mostly combinations of the different compounds are added to a broad variety of food, drinks, drugs, and hygiene products complicates a systematic analysis of their potential impact on the development of urological malignancies. Nevertheless, so far not a single study has convincingly demonstrated a statistically significant risk of bladder cancer due to the consumption of artificial sweeteners. This survey demonstrates that the individual assessment of lifestyle factors not only may identify groups with an increased risk for urological malignancies but also clearly displays a potential for tumour prevention.

Tobacco Use, Occupation, Coffee, Various Nutrients, and Bladder Cancer2

In a Canadian population-based case-control study of 480 males and 152 female case-control pairs, the relative risk for development of bladder cancer for ever used versus never used cigarettes was 3.9 for males and 2.4 for females, with a dose-response relationship in both sexes. A reduced risk was associated with the use of filter cigarettes compared to nonfilter cigarettes. After control for cigarette usage, a significant risk was noted for male pipe smokers. For male ex-smokers the risk after 15 years of no smoking was less than one-half that of current male smokers. Bladder cancer risk was found for workers in the chemical, rubber, photographic, petroleum, medical, and food processing industries among males and for workers occupationally exposed to dust or fumes among both sexes. Bladder cancer risk was elevated for males consuming all types of coffee, regular coffee, and instant coffee and for females consuming instant coffee, but no dose-response relationship was found. Risk was found for males consuming water from nonpublic supples but not for females. No risk was observed in males or females consuming nitrate-containing foods, beverages other than coffee, or fiddlehead greens. Hair dye usage in females and phenacetin usage in males and females carried no risk. Divergent findings by area for aspirin suggested that an overall association was not causal. Reevaluation of the data on artificial sweeteners confirmed a significant bladder cancer risk in males and a dose-response relationship. The cumulated population attributable risk for bladder cancer was 90% for males from cigarette smoking, industrial exposure, and exposure to nonpublic water supplies and 29% for females from cigarette smoking, industrial exposure, and instant coffee consumption.