During the years 1979-1981 a population-based case-control study of bladder cancer including papilloma was performed in greater Copenhagen. A total of 371 patients (280 males; 91 females), and a comparable age- and sex-stratified group of 771 controls (577 males; 194 females) remained for logistic regression analysis. Controls were selected at random from the general population of the study area. All persons were questioned about their drinking habits with respect to coffee, tea and other beverages, as well as their exposure to a number of known or suspected risk factors for bladder cancer. After adjustment for tobacco smoking, the relative risk of bladder cancer in relation to coffee drinking was not statistically significant among either men or women. A significant association was found between bladder cancer and tea drinking among men, but with no regular trend for increasing consumption. An association was found between risk of bladder cancer and both total daily liquid intake and non-cola soft drinks. This population-based case-control study provides no evidence of an isolated influence of coffee drinking or caffeine intake on bladder cancer risk.
A population based study of 388 cases of bladder cancer including papillomas and 787 controls in Greater Copenhagen confirmed the role of smoking in the aetiology of bladder cancer. Significantly increased relative risks were found for persons who had smoked only cigarettes (RR = 2.9; both sexes combined) and for mixed smokers including cigarettes (RR = 3.6; both sexes combined). Multiple logistic regression analysis showed significant influences of the amount (pack years) of cigarettes smoked and a reduced risk among persons who had stopped smoking. No significant effects of smoking pipe or cigars/cigarillos were apparent, and the present study does not confirm previous suggestions of associations between the smoking of cigars/cigarillos and bladder cancer in Denmark. Only a slight increase in relative risk with the amount smoked was found. The influence of smoking on bladder cancer risk was similar for tumours in stages T1 and T2-4 at diagnosis and also for tumours of grades 1-2 and grades 3-4 at diagnosis.
Urothelial cancer has been linked with tobacco, phenacetin-containing analgesics and some industrially-related carcinogens. Carotene has been suggested as reducing the risk of urothelial cancer but there is not much information on the relation between diet and the incidence of human urothelial cancer. Furthermore, the magnitude of the risk of urothelial cancer for pipe smokers remains unclear. In a 14-year follow-up of 16,477 Swedish twins the rate ratio of urothelial cancer (with 95% confidence interval) for subjects with a moderate/high intake of pork and beef respectively was 1.6 (1.0-2.7) and 1.6 (1.0-2.6). Meat consumption is widespread in Western populations. If the finding is supported by further data, a possible etiologic factor associated with the consumption of beef and pork would account for a substantial proportion of the cases of urothelial cancer. The rate ratio for men smoking a pipe/cigars, but not cigarettes, was 3.3 (95% confidence interval 1.5-7.4).
PURPOSE: We determined whether base and nucleotide excision repair is activated in bladder urothelium by chronic persistent low doses of ionizing radiation in male patients with benign prostate hyperplasia and females with chronic cystitis living more than 15 years in Cs contaminated areas after the Chernobyl accident in Ukraine. MATERIALS AND METHODS: Bladder urothelial biopsies from 204 patients were subjected to histological examination and biopsies from 35 were subjected to immunohistochemical study of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A endonuclease. RESULTS: Chronic proliferative atypical cystitis with multiple foci of dysplasia and carcinoma in situ were observed in 139 (89%) and in 91 (58%) of 156 group 1 patients from radio contaminated areas, respectively, as well as 10 small transitional cell carcinomas. Chronic cystitis with areas of dysplasia was detected in 9 of 48 patients (19%) in control group 2 from clean (without radio contamination) areas of Ukraine. Greatly elevated levels of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A were evident in the urothelium in group 1, accompanied by increased Cs in the urine. CONCLUSIONS: These findings support the hypothesis that significant activation of DNA damage repair (base and nucleotide excision repair) is induced by the oxidative stress generated by long-term low doses of ionizing radiation. The levels of DNA oxidative adducts pointing to mutagenic and carcinogenic potential were in line with the histopathologically diagnosed urothelial lesions.
A prospective study of all patients with superficial bladder cancer diagnosed in Northern Alberta (population 1.2 million) from 1977 to 1983 was performed to establish patterns of recurrence. Of the 761 patients with all stages of bladder cancer at diagnosis, 642 were deemed to be free of disease after primary treatment consisting of transurethral resection, fulguration, or laser surgery. Follow-up of these patients showed that approximately two-thirds of first recurrences occur within 18 months of diagnosis and that more of these patients have died of unrelated causes (n = 73) than of bladder cancer (n = 34). Censored disease-free interval comparisons showed that initial recurrences occurred sooner in patients with multifocal rather than unifocal disease and also sooner in females than in males. Known risk factors (occupational exposure to chemicals and cigarette smoking) and suspected risk factors (coffee consumption and artificial sweetener use) had no effect on disease-free interval and are not related to tumor multiplicity.
We have previously shown that bladder urothelium of people living in the cesium-137 ((137)Cs)-contaminated areas of Ukraine demonstrates accumulation of stable p53 and p53 mutational inactivation, preferentially through G:C to A:T transition mutations at CpG dinucleotides, with a codon 245 hot spot. In the present study, we analyzed immuno-histochemically the relationship between oxidative stress markers and over-expression of p53 and H-ras in urinary bladder urothelium from 42 men with benign prostatic hyperplasia. Bladder mapping biopsies were obtained from 15 patients from a highly radiocontaminated area (group I), 14 patients from the less contaminated city of Kiev (group II) and 13 patients as a control group from "clean" (without radiocontamination) areas of Ukraine (group III). Irradiation cystitis with multiple foci of severe dysplasia and carcinoma in situ were observed in 15 of 15 (100%, group I) and 9 of 14 (64%, group II) cases, with 4 small transitional-cell carcinomas incidentally detected in groups I and II. Markedly elevated levels of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and 8-hydroxy-2;-deoxyguanosine (8-OHdG) were noted in these bladder urothelial lesions from groups I and II, accompanied by strong over-expression of p53 and less H-ras expression. These findings support the hypothesis that iNOS, COX-2 and 8-OHdG in bladder urothelium are induced by long-term exposure to low-dose radiation with a close relationship to p53 over-expression that could predispose to bladder carcinogenesis.