Is Bladder Cancer More Common among Opium Addicts? ASGARI MA*, KAVIANI A, GACHKAR L, HOSSEINI-NASSAB SR Department of Urology, Shaheed Modarress Hospital, Shaheed Beheshti University of Medical Sciences, Tehran, Iran ABSTRACT Purpose: Many environmental and occupational risk factors have been proposed for bladder cancer, among which opium consumption has been considered in few studies. We designed a study to determine the relationship between opium consumption and bladder cancer. Materials and Methods: In a retrospective, case-control study, male patients with bladder cancer, who had been referred to our hospital in a three-year period, were selected. Data regarding age, gender, smoking, and opium consumption were collected from patients' records and compared with data of a control group, consisting of patients with benign prostatic hyperplasia (BPH). Results: Fifty-two male patients with bladder tumor (group 1) were compared with 108 patients with BPH (group 2). Of the patients with bladder cancer, 36 (68%) were smokers, of whom 12 were also opium addicts. In general, 13 (25.5%) patients were opium consumers (one opium consumer was not smoker). From 108 patients with BPH, 25 (23%) were smokers, of whom, 5 were also opium addicts. Mean duration of cigarette smoking was 31 ± 13.6 and 20.2 ± 14.7 years in patients with bladder cancer and BPH, respectively. The duration of opium consumption was 11.9 ± 1.4 and 6.2 ± 1.3 years in groups 1 and 2, respectively. The duration of cigarette smoking and opium consumption in group 1 was greater than that in group 2. In addition, smoking increases the risk of bladder cancer 3.8-fold (OR = 8.3, 95% CI = 1.8-7.8). Simultaneous cigarette smoking and opium consumption increases the risk of bladder cancer 6.2-fold (OR = 6.2, 95% CI = 2.04-18.7). Conclusion: There are few studies regarding the carcinogenic effect of opium on bladder. We demonstrated that, the incidence of bladder cancer in smokers, who are simultaneously opium consumers, was higher than in patients who were only smokers. Simultaneous opium addiction and cigarette smoking may have some roles in the pathogenesis of bladder tumor. However, further studies with large sample sizes are warranted. KEY WORDS: bladder cancer, risk factors, cigarette smoking, opium addiction 253 Urology Journal UNRC/IUA Vol. 1, No. 4, 253-255 Autumn 2004 Printed in IRAN Introduction Bladder cancer is the fourth common cancer in men and the eighth in women.(1) The known risk factors are smoking, little water consumption, Aristolochia (a Chinese herb using to lose weight), exposure to aromatic amines, immuno- suppressives, cyclophosphamide, radiotherapy, arsenic, chronic cystitis, and with in all probabil- ity, tea and coffee.(2) Few researchers have also proposed opium as a risk factor for bladder can- cer, but there is not enough evidence of carcino- genic effect of opium in bladder malignancies. We designed this study to determine the relationship between opium consumption and bladder cancer. Materials and Methods In a case-control study, all of the male patients with a pathological diagnosis of bladder cancer or Received December 2003 Accepted November 2004 *Corresponding author: Department of Urology, Shaheed Modarress Hospital, Sa'adatabad Ave., Tehran, Iran. Tel: +98 912 118 6460 Bladder Cancer and Opium Addiction BPH, who had undergone surgery in Shaheed Modarress Medical Center, between 1997 and 2000, were reviewed. Data regarding age, gender, cigarette smoking, and opium consumption, and the duration of smoking or addiction were collect- ed from patients' records. Patients with bladder cancer and BPH were considered as subjects (group 1, 52 cases) and controls (group 2, 108 cases), respectively. Females were excluded from this study in order to achieve more matched groups. The age range was 48 to 75 years and mean age was 67.5 ± 7.4 and 65.3 ± 9.8 years in group 1 and 2, respectively. The statistical analy- sis was done using Chi-Square and Odds Ratio tests. The P value less than 0.05 was considered significant. Results The mean age was 61.2 ± 16.6 (median 61.5) years in the patients with bladder cancer and 67.0 ± 7.4 (median 65.5) years in those with BPH. Without considering opium consumers, 36 patients (68%) with bladder cancer and 25 with BPH (23%) were smokers (P <0.01). The probabil- ity of cigarette smoking in patients with bladder cancer (with and without opium consumption) was 7.5-fold greater than that in patients with BPH (OR = 7.5; 95% CI = 3.6-15.6). The rate of simultaneous cigarette smoking and opium consumption was 23.3% and 4.6% in groups 1 and 2, respectively (P <0.001, table 1). In comparison with control group, the probabili- ty of simultaneous cigarette smoking and opium consumption in patients with bladder tumor (group 1) was 6.2-fold greater (OR = 6.2; 95% CI = 2.04-18.7). Excluding opium consumers, the rate of cigarette smoking was 46.1% and 17.3% in groups 1 and 2, respectively (P <0.001) and the probability of cigarette smoking in patients with bladder tumor was 3.8-fold greater in comparison with control group (OR = 8.3; 95% CI = 1.8-7.8). Regular cigarette smoking duration was signifi- cantly longer in patients with bladder cancer than in control group (P <0.005, table 1). Also, opium positives in group 1 had a longer history of opium consumption (P <0.0001, table 1). The likelihood of bladder cancer in association with simultaneous cigarette smoking and opium consumption is twice in comparison with only smoking. There was not any significant relation- ship between opium consumption and bladder tumor. Discussion The prevalence of cigarette smoking and opium consumption is relatively high in Iran.(2) Although various studies have been done on the carcino- genic effect of opium in esophageal cancer in the northeast of Iran, studies regarding its relation- ship with bladder cancer are scarce. Investigations on the prevalence of esophageal cancer in the northeast of Iran have shown its association with opium, especially the burned form, (opium pyrolysates).(3-7) Cigarette and alco- hol are the most important risk factors of esophageal cancer; ethanol increases DNA alka- lization in mucosal cells and it has been reported that high doses of morphine can have the same effect in rats.(8) Accordingly, narcotic agents may have the same pathogenesis that can lead to malignancy. This study demonstrated that the number of smokers and opium addicts are higher in subject group. In addition, simultaneous cigarette smok- ing and opium consumption increases the likeli- hood of bladder tumor 2-fold in comparison with only smoking. However, due to the paucity of opium-only consumers (one patient), the correla- tion between opium and cancer could not be assessed in our study. Sadeghi and co-workers in Shiraz showed that of 3500 opium addicts, 15 had bladder cancer, while the prevalence of bladder cancer in the respective province was 6.6 in 100000. They concluded that, opium is a risk fac- tor for bladder cancer.(2) Nonetheless, 85% of patients had been smokers, and of 15 patients with bladder cancer, 14 were smokers, so that only simultaneous smoking and opium consump- tion could be considered as the risk factor for bladder caner. Documentation of the carcinogenic effect of opium on bladder tumor requires further studies with purely opium addict subjects, but due to the paucity of such a population, it is not viable unless through a great scale study. Also, animal experimental studies can shed light on this issue. 254 TABLE 1. Statistic data of the patients in groups 1 and 2 � ��������� �� ���� ���������� ���������� ��������� �� ������ ���������� ������� ��� ���� ���������������������������� ��� �� �� ��� �� �� ���������������� ��� ���� �� �� �� �� ����������� � � � ��� �� ��� ���� �� ������������������� � �� ���� �� �� � �� ������!��������������������� ��� ���� �� �� �� �� �������� �������� ������������ ������� ��� ���������������� �������� ��������� � ���������� � Asgari et al Conclusion It seems that simultaneous opium consumption and cigarette smoking plays a role in bladder tumor pathogenesis, but for clarifying the effect of opium, separately, further studies with greater subjects are needed. References 1. Messing EM. Urothelial tumors of the renal pelvis and ureter. In: Walsh PC, Retik AB, Vaughan ED Jr, et al, editors. Campbell's urology. 8th ed. Philadelphia: WB Saunders; 2002. p.2737-41. 2. Behmard S, Sadeghi A, Mohareri MR, Kadivar R. Positive association of opium addiction and cancer of the bladder. Results of urine cytology in 3,500 opium addicts. Acta cytol. 1981;25:142-6. 3. Ribeiro Pinto LF, Swann PF. Opium and oesophageal cancer: effect of morphine and opium on the metabolism of N-nitrosodimethylamine and N-nitrosodiethylamine in the rat. Carcinogenesis. 1997;18:365-9. 4. Friesen M, O'Neill IK, Malaveille C, Garren L, Hautefeuille A, Bartsch H. Substituted hydroxyphenan- threnes in opium pyrolysates implicated in oesophageal cancer in Iran: structures and in vitro metabolic activa- tion of a novel class of mutagens. Carcinogenesis. 1987;8:1423-32. 5. Ghadirian P, Stein GF, Gorodetzky C, et al. Oesophageal cancer studies in the Caspian littoral of Iran: some resid- ual results, including opium use as a risk factor. Int J Cancer. 1985;35:593-7. 6. Friesen M, O'Neill IK, Malaveille C, et al. Characterization and identification of 6 mutagens in opium pyrolysates implicated in oesophageal cancer in Iran. Mutat Res. 1985;150:177-91. 7. Malaveille C, Friesen M, Camus AM, et al. Mutagens pro- duced by the pyrolysis of opium and its alkaloids as pos- sible risk factors in cancer of the bladder and oesopha- gus. Carcinogenesis. 1982;3:577-85. 8. Hewer T, Rose E, Ghadirian P, et al. Ingested mutagens from opium and tobacco pyrolysis products and cancer of the oesophagus. Lancet. 1978;2 494-6. Editorial Comment As the authors acknowledged in this retrospec- tive study, the data regarding opium consumption were from the patients' record. Due to legal and social aspects of opium consumption, such retro- spectively collected data could not be accurate. Also due to the paucity of sample size, one can- not separate smokers from opium addicts. As a result, estimating the independent effect of opium on bladder cancer is not valuable. The results with wide confidence intervals are due to the little sample size. However, it should be noted that conducting a prospective and comprehensive research on the issue is not easily possible, and since there are few studies showing the associa- tion of simultaneous cigarette smoking and opium consumption with bladder cancer, the result achieved in this study are valuable. Ziaee SAM Urology/Nephrology Research Center 255