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F....-- be protected by copyright law (We 17 U.S. Code). .. Analysis of Known Risk Factors for Bladder Cancer in Pakistani Population Altaf HussainHashmi, Ali Anwar Naqvi and Adibul Hassan Rizvi Sindh Institute of Urology and TmsplpntPtioq Dow Medical College, Karachi. Abstract ., The association of aetiological agents indminated for bladder cancer are well recognised. They are divided into two groups, occupational and non-occupational.The commonest occupational agents are 2-naphthylamine, benzidine, aminobiphenyl, dichlorobenzidine, orthodianisidine and orthotolidine. Recognised non-occupational agents include tobacco, recurrent chronic bladder infectiodmfestatian,, coffee and drugs. This study was conducted to evaluate these factors in patients with bladder cancer in our population. Of 250 cases studied, 203 were males and 47 females with a male to femaleratio of 431. In.13.6%cases occupational factom were established with an average duration of exposure of 12 years. Majority(68%)of patientshadsmokingas the predominantnon-occupationalfactor.Inthisgroupaverage cigarettes smoked per daywas 23 with a range of 15 to 90. The duration of smoking ranged between 5 to 55 years with an average of 26 years. Sixty patients (24%)were neither smokers nor had any associated high risk occupation(JPMA45: 41,1995). Introduction The association between environmental agent that could cause the development of a malignancy was first describedby Percival Pott in 1775who reportedscrotalcancer in ckmney sweeps'. Seved carcinogenic agents causing bladder cancer both occupational and non-occupational are well nxogxused. The incidenceof bladder cancerattributedto occupational eqosure is between 8% and 200h*.The most common occupational carcinogens are 2- naphthylamine, benzidine, aminobiphenyl,dichlorobenzidine,orlhodianisidine, orthotolidine,phenacetin,chlornaphazineandcyclophos- phamideZ4.Epidemiologic studies by Case and co-workers showed that the mean latent period may be as long as 40 to 50 years, however, time period may be diminished in patients who havehigherexposureto carcinogens5.Mean latentperiod fortumours in the rubberand chemical industry was 25 years. Factors recognised as non-occupational carcinogens include tobacco6,excessiveexposureto motorvehicleexhaustfumes' chronicurinary tract infection', schistosomiasis*,saccharine', coffee" and drugs''.". Both retrospective and prospective studies have shown that there is an increased risk of developingbladder cancer in cigarettesmokers'.'". Thij study has analysed these risk factors in patients with bladder cancer in local population This evaluation is important since bladder cancer ranks loth amongst the commonestmalignanciesinmalesin Pakistanandisontopof the list ofurologicaImaIignancies". Patients and Methods The study isbased ondata collectedfrom 250 consecutive patients of carcinoma of urinary bladder admitted in the SindhInstituteofUrology~dTransplantationD, ow Medical College,Karachi,between 1988-1991.Diagnosticcriteriaand assessment included deiailed clinical history, clinical esamination, laboratory investigations, intravenous urography, ultrasound, esfoliative urinary cytology, CT scan (where indicated), cystoscopy and biopsy. Final diagnosis was established after histopathological examination of biopsied tissue. Theereafter a detailed history of known etiological factors was documented on a proforma to include the followingoccupationaland non-occupationalrisk factors. Occupational factors include chemicalslike petroleum products @]ant processing petroleum products), dyes like benzidine compounds used in textile printing, tailoring and hairdyesused by hairdressorsandrubberarticlecontaining0- nephthylamine. Non-occupatiod factors include cigarette smoking,drugs like phanacetin, cyclophosphamidsandchlornaphazin andchronic infectiodinfestationof bladder. Results Of the 250 wes,203 were males and 47 females with a male to female ratio of 4.3:1. Age distributionranged from 14 to 81 years and peak age group was between 51 to 60 years. Etiological factors were evaluated in each patient (Table I). Table 1. Erwiromnenralfactors for bladder w a r . OCCUpuiOlL3 Incriminated chemical agents No. % A. ( k c U p d O M 1 I. Chemicals P a l pump workers Sui gas workers 11. Dyes Textileprinting Tailoring Leatherwoks Hair dressing 111Rubber articles Rubber industry Petrochemical compounds Natural gas &Nidmcompound &midine compound Benzidine compound Benzidine compound f3 -naphthylamine 11 4.4 2 0.8 .. . 7 2.9 6 2.4 4 1.e I 0.4 3 1.2 B. Non-Occupationnl Cigiuette smoking 170 68 41 J.Pak.Med.Assoc Thirty-four (13.6%) had established oaxpational and I70 cancer of today represents the working practices of 25 years (68%) non- occupational factors. In the occupational group ago,thesamemay apply toourpatients.Withtheadventofthe 7.1%cases had exposure to benzidinecompoundsliketextile development of chemical industries in Pakistan,we need a printing, tailoring and hair dressing. Thirteen(5.1%) patients candidview speciallyof indusviesusing high risk chemicals. were exposed to petrochemicalcompounds and natural gas. Cigarette smoking has been identified as an important -** Three patients had long history of exposure to beta-naphthylamine in rubber industry. The duration of exposure varied risk factor for bladder cancer and the cause and effect relationshiphasbeenidentifiedby several Various from 3 to 15 years with an average duration of 12 years. measures have been used to assess the magnitude of the Majority of patients (68%) had one non- occupationalfactor, relationship between smokingand bladder cancer, i.e., num- i.e., smoking(Table I) while no otherfactorwas recognised berof cigarettessmokedanddumtionof cigarettesm~king'~~~. Thenumberofcigarettessmokedperdayvariedfrom15 Ourdatasupportsthe contentionsthatcigarettesmoking is the to 90, theaveragebeing 23 cigarettesperday.Sixtypercentof most consistent finding in the epidemiological studies of patients smoked upto 20 cigarettesper day while 12.2% were bladder cancer. heavy smokexs,i.e., more than30 cigarettesper day (Table II). In60patients no knownfactorscouldbeidentified.This The duration of smoking ranged between 5 to 55 years, the group which constitutes 24% of our patients needs further averagebeing 26 years. Majority (88.2%) of patients smoked evaluation for possible etiological factors prevalent locally. for 10to 40 years and small number (4.7%) for more than 40 This initial study highlights the need for a more detailed re years (Table III). Of the 80 patients with bladder cancer who multicentre study to identlfy etiological factors for bladder <as were non-smokers, only 20 (25%) had high risk occupations. cancer in Pakistan. :d ai Tabls 11. Number ofctgmnes smokedin non-occupational group. References he No of ctgarettalday No ofpatients 06 oftod C Y C S I Calalona, L. Bladder cancer in adult and pediatric urology Edited by J Y m <IO ke 11-20 21-30 :Id 31-40 Gillcnwater.J T. Grayhacli S.S.Howardsmd J.W. Ducken. SI. Lwis. Morby. 37 21.7 1991.pp. 1135-75 65 38.2 2 Wallace. D M A. Occupauonal urothclial cancer.Br I. Urol.. 1988.6I :I 75-62 47 27.6 3 Rubben, H . Lutzcycr, W. and Wallace. D.M.A. The epidemiology and 16 9.4 aetiology of bladder cancer m bladder cancer. Edited by E.I. Zingg. E.J.and 3- 41-50 ite >XI )r- 3 I .7 D.hi.A. Wallance. New York.Springer- Verlog. 1985.p~.1-21. 2 1.1 4. The BAUS subcommittee on industrial bladder cancer. Occupationalbladder cancer: Aguidcforclinicianr. Br. J. Urol.. 1988;61:183-191. 5. Case. R.A.M. Hosker. ME.. McDontld, D.B. d al. Tmoun of the urinary bladder in workman engaged in the manufacture and UY ofc a i n dye stuff Table 111. P m t i o n ofsmokingin ycan in non-occupiional group. urtermediaretnthcBritishchanicalindustry.Br. J h d . Med.. 1954:11~75-104 6 Amstrong. B. and Doll. R. Bladder cancer monality VI England and Wala in Duration in yean No. of patients %of total cases relation lo cigarette smoking and Saccharine consumption Br. J Prev. Soc Mal., 1974:28:233-40. <IO i a 10-20 14 21-30 31-40 E. 41-SO 14 54 82 31 7 7 Wynder. E.L. and Gold Smith R. The Epidemiology of bladder cancer' A second look Cancer. 1977;40:1246-68. 8 U?t. D C. and Zinckc. H. The muqueradc of bladder cancer in Situ as 65 38 2 intustitial cystitis.1. Uml.. 1974.1I I:60-61. 31 18.2 9. Cohen. S M..Arai. M..Jacobs. J.B. cI al. PromoungeITecu ofucchanne and 4 2 3 DL-Tryptophan in u r m q bladder carcinogcnais. Cancer Res.. 1). >%I 4 2.3 I9W.39:1207-17. IO. Cole. I? C o t k drinking and cancer of the lower urinary tract. Lancet. - Discussion 1971:I :1335-7. I I . Gonwa. T.A.. a r b - W.T.. Schey, H.M d al. Analgesi- arrocia(cd Historically in 1885bladdercancerwasthefirsttumour *' idcaitied where an BSSOC"InB~w~aOsestablisbdbuween chemicalsexposureand developmentof canad'. Sincethen nephropathy ud tnnsilional cell uninoaud t h c urinarytnd.Ann. Intcm. Mrd.. 198093249-52, 12. pMaL R M and Sobway. MS. D m cycbpboqh.mide induce bladder uma?Urology. I9m.4437. . 13. Hoover, R and Cole, P.Population umda in cigarette mokq and bladder . several chemicals used in various industries appeared as causativefactorsofbladdercancer.Thus8-20%ofthebladder cancer we= attributed to be caused by exposure to chemi- cancer. A m I.Epidaniol.. 1971:94:409-18. 14. Iafarcy, N.A. and Zaidi. S.H.M c.nScr in RkisIan. I. Pak M a l . AIOS.. 19m,37:178-83. 15. Alderson.M O c c u p a t i o ~ ~ l c u ~BcruJ..Uml.. 1986;13:119-61. &'6, while persuing occupations in gas, petrochrmical 16. Canwight. R. Occupational bladdu cancer and ciguc(tc smoking in West indusuy,rubberin dust^^,dyeingandtextileindustries, leather worksandtailoMg,etc. In thesestudiesthefrequencyof such Yorkshire. Scand. 1.Work Environ. Halth(Supp1.) 1982.8:79-82. 17. Cole.P. A population b a d study ofblddcr cancer. In honenvironmenul i n t d c t i a u m the etiology of CMCQ in Man. Scianifii Publication No. 7. occupational bladder cancer varied between geographical I973.p~.83-87. ngions,dependingupon~typeandconcenUabionwithinan 18. Gubcran. E.. Raymond. L. and Swoanem. P.M Incrcued nrk for male bladder cancer among a cohort ofmale and female hairdress- in Geneva. area of chemical industries. Our data of 13.6% of bladder InL I. Epidaniol.. 1985;14:549-54. callcer where occupational association was identified corroborates with Western repom. Since in the Western reports 19. M~rrcctL. .D ,Huge.P.and Meigs. I.W. Bladder cancer and occupational exposure lo leather. Br. I. Ind. Med., 1986;43:%- 100. 20. Anthony. H.M. and Thomas. G.M. Bladder tunours and smoking. InL 1. exposure period varied from 5 to 25 years, the urothelial Cancer. 1970:5.266-272. b VOl. 45. N0.2. February. 19% 42