Water chlorination and other environmental factors in bladder cancer. Result of a multicentre study

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V. Serretta1, V. Altieri2, G. Morgia3, L. Cindolo4, R. Allegro1, A. Di Lallo5, D. Melloni6, C. Magno6, M. Motta7, L. Salzano4, A. Saita7, F.P. Selvaggi8, G. Annunziata8, G. Testa9, D. Sblendorio10, M. Pavone-Macaluso1, Gruppo Uro-Oncologico Campano11, and Gruppo Studi Tumori Urologici12
1University, Urology, Palermo, Italy, 2University, Urology, Napoli, Italy, 3University, Urology, Sassari, Italy, 4Civic Hospital Rummo, Urology, Benevento, Italy, 5Civic Hospital, Urology, Campobasso, Italy, University, Urology, Messina, Italy, 7University, Urology, Catania, Italy, 8University, Urology, Bari, Italy, 9-Civic ospital, Urology, Napoli, Italy, 10Civic Hospital, Urology, Carbonara (BA), Italy, 11Campania, Italy, 12Sicilia, Calabria, Campania, Molise, Puglia, Italy

 

INTRODUCTION & OBJECTIVES
Although the role of cigarette smoking and occupation in bladder cancer has been extensively studied, that of other environmental and lifestyle factors is not yet defined (1-4). Moreover, only few studies have evaluated the role of each factor in a multivariate analysis and have correlated them with relevant prognostic factors of
the tumor such as grade, stage, multiplicity and recurrence rate. These factors have been prospectively related to recurrence and progression rate.
There is a growing evidence that chlorination may play an important role in the development of bladder cancer. Community water supplies in Italy, like in many other countries, adopt chlorine as a disinfectant..
In Southern Italy, due to the variable quality of the water supply coming from municipality and from natural sources, a large amount of the population in the last 30 years adopted bottled mineral water as the main drinkable water supply. The present investigation is the preliminary pilot step of a larger case-control study in which two different cohorts of subjects drinking either bottled or municipal water will be compared.

MATERIALAND METHODS
The analysis was limited to patients affected by intermediate risk superficial TCCB. Patients with primary single Ta G1-2, Tis or T1G3 tumors were excluded. Forty Italian urological centres joined the study. Detailed information about age, sex, residence, employment, active and passive cigarette smoking, water resource, and hair-dye use, was obtained. Patients living in rural areas and small centres were compared with those living in cities with more than 15000 inhabitants.

For working activity 3 main categories were considered:
1. Agricolture, 2. Service, 3. Industry.

The information on water supply included the source of water, unique or mixed to other sources, and the length of consumption from each source. All patients underwent TUR and early intravesical chemotherapy within 6 hours. The drug adopted in all cases was epirubicin, 80 mg diluted in 50 ml of saline solution, maintained in the bladder for a hour. The distribution of the above mentioned environmental and life-style
factors was analyzed in relation to tumor characteristics such as multiplicity and previous recurrence rate.

RESULTS
Between May 2002 and December 2003, 577 patients have been recruited. The characteristics of the patients are reported in table I. The distribution of the risk factors considered in our study is shown in figure I. Cigarette smoking and hair dye use are analyzed in table II. Out of 577 patients, 427 (74.5%) were smokers or ex-smokers with a median number of 20 cigarettes per day. The median smoking period was 30 years. Forty-seven patients (8.2%) had been using hair dye for a median period of 10 years. The only water resource was municipal chlorinated water in 31.4% and bottled water in 44.5% of patients for a median period of 17 and 15 years respectively.
At multivariate statistical analysis (table III) a significant correlation was found between tumour multiplicity at first diagnosis and at subsequent recurrences and employment in agricolture or in industry at risk (p=0.03) and between number of recurrences and period of cigarette smoking (p=0.04). A significant correlation emerged between water source, cigarette smoking and bladder cancer (p=0.05). The municipal
water supply was, in fact, the only water source more frequently in non-smokers (36%) than in smokers (30%). This observation might imply water resource and chlorination as an enviromental risk factor.

CONCLUSIONS
Employment in industry and agricolture was related to multiplicity of the tumor at first diagnosis and at further recurrences (p=0.03). The number of previous recurrences (p= 0.04) was related to the lenght of the exposure to cigarette smoking. Drinkable water source seems to be implied as a risk factor in superficial bladder cancer in absence of cigarette smoking (p=0.05).

ACKNOWLEDGEMENTS
We wish to thank all the co-Authors of the present study: G Carrieri, PAnnese (Matera), A Zito (Torre del Greco), A Gallo (Napoli), V Cosentino (Gela), FP Selvaggi (Bari), L Borruso (Salemi, Trapani), S Chincoli (Trani, Bari), A Bartolotta (Partinico), G Vaccarella (Palermo), G Ruggero (Telese Terme, Benevento), F Vacirca, C Cammarata (Caltanissetta), A Armenio (Palermo), NS Simone (Caserta), F Falvo (Catanzaro), M
Gentile (Avellino), D Nicolosi (Catania), A Saracino (Bari), A Masala (Napoli), A Bizzini (Caltagirone), M Napoli (Trapani), A D’Elia (Castellaneta, Taranto), F Aragona (Catania), E Gange (Palermo), V Ricci Barbini (San Giovanni Rotondo, Foggia), A Spampinato (Taormina, Messina), G Curto (Palermo), G Raguso (Martina Franca, Taranto), Q Paola (Sciacca, Agrigento), A Crimi (Castellamare di Stabia, Napoli), V Cicalese
(Avellino), and the all members of the GUOC and GSTU. The study was supported in part by an unrestricted grant from Pfizer Italia Srl.

REFERENCES
1. Siernietycki S, Dewar R, Nadon L: Occupational risk factors for bladder cancer: results from a case-control study in Montreal, Quebec, Canada. Ann, J. Epidemiology, 140: 1061-80, 1994 - 2. Freedman DM, Cantor KP, Lee NL, Chen LS, Lei HH, Ruhl CE, Wang SS: Bladder cancer and drinking water: a population-based casecontrol study in Washington County, Maryland (United States). Cancer Causes and Control, 8: 738-744, 1997 - 3. McGeehin MA, Reif JS, Becher JC, Mangione EJ: Case-control study of bladder cancer and water disinfection methods in Colorado. Am J Epidemiol, 38: 492-501, 1993 - 4. Cantor KP, Lynch CF, Hildeshiem M: Chlorinated drinking water and risk of bladder, colon and rectal cancers: a case-control study in Iowa, USA Epidemiology: abstract 6 (Suppl.): S30, 1995


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