Subproductes de la desinfecció de l'aigua potable i càncer de bufeta urinària

Antecedents: La cloracio de laigua genera trihalometans (THM) i altres subproductes de la desinfeccio (DBP) amb propietats carcinogenes. Lexposicio a llarg termini a aquests compostos sha associat amb un increment del risc de cancer de bufeta, pero les evidencies no son concloents. Objectius: -Determinar lexposicio a THM com a indicadors del total de DBP en la poblacio destudi. -Estimar el risc de cancer de bufeta per exposicio a THM. Metodologia: (1) Meta-analisi destudis sobre consum individual daigua clorada i cancer de bufeta. Es va fer una cerca bibliografica i es van seleccionar estudis que avaluaven cancer de bufeta i consum individual daigua clorada a llarg termini, tot incloent sis estudis cas-control (6084 casos de cancer de bufeta, 10816 controls), i dos estudis cohort (121 casos) que complien els criteris dinclusio. Es van extreure les odds ratios (OR) o els riscs relatius (RR), mes els intervals de confianca al 95% (95%CI) per sexe i categoria dexposicio. Es va fer una meta-analisi per les diferents categories dexposicio. (2) Analisi de dades combinades (pooled analysis) de sis estudis cas-control de cancer de bufeta, que proporcionaven dades quantitatives sobre nivells dexposicio a THM i consum individual daigua. Shan inclos dos estudis dels EEUU, i un de Canada, Franca, Italia, i Finlandia respectivament. Es van extreure de les bases de dades originals variables dexposicio i covariables, combinant-se tot seguint definicions comunes. Lanalisi inclou 2806 casos i 5254 controls. Es va calcular lexposicio acumulada a THM (mg). Les OR i 95%CI es van estimar a traves de regressio logistica tot ajustant per estudi i factors confusors potencials. (3) Estudi multicentric cas-control de cancer de bufeta. La poblacio destudi prove de 18 hospitals participants a Asturies, Alacant, Barcelona i Tenerife. Sha avaluat lexposicio a THM de la poblacio destudi a traves dentrevistes personals a 1226 casos i 1271 controls, determinacions de THM a mostres daigua, i recull de dades retrospectives de THM a traves de questionaris a empreses daigua i ajuntaments. Es calculen les OR i 95%CI a traves de regressio logistica per categories dexposicio a THM tot ajustant per area i factors de confusio potencials. Lanalisi es limita als individus amb informacio dexposicio =70% de la finestra dexposicio, tot excloent-se individus amb qualitat global de lentrevista questionable o insatisfactoria. Resultats: (1) Haver consumit alguna vegada aigua clorada sassocia amb un increment del risc de cancer de bufeta en homes (OR combinada=1.4, 95%CI=1.1-1.9) i dones (OR combinada=1.2, 95%CI=0.7-1.8). (2) Les OR ajustades en homes exposats a >15 mg THM, comparats amb els exposats a 1000 mg (p trend <0.001). En les dones, lexposicio a THM no sassocia amb un increment del risc. (3) Les arees destudi amb major exposicio son Alacant i Barcelona amb nivells mitjans de THM al 1999 de 85.9 i 63.5 mg/l respectivament. Tenerife presenta els nivells mes baixos (8.0 mg/l) i Asturies nivells intermedis-baixos (22.3 mg/l). La OR en homes per exposicio mitjana a THM per ingestio >35 mg/dia en relacio a 0 mg/dia era de 1.55, 95%CI=1.02-2.35. Els homes que han estat a la piscina >630 hores al llarg de la vida tenen una OR de 2.08 (95%CI=1.06-4.09) respecte els que mai havien nedat. Conclusions principals: 1. Algunes poblacions espanyoles estan altament exposades als subproductes de la cloracio, tant en lactualitat com en el passat 2. Els resultats conjunts reforcen la hipotesi que lexposicio a THM a llarg termini, a nivells que sobserven en molts paisos industrialitzats, sassocia amb un increment del risc de cancer de bufeta. 3. El genere resulta ser modificador de lefecte, amb una major associacio observada en homes. 4. Trobem una associacio entre assistencia a piscines i risc de cancer de bufeta. Aquests resultats shan dinterpretar amb precaucio donat que es el primer estudi que avalua aquestes vies dexposicio i calen estudis confirmatius. Background: Chlorination of drinking water generates trihalomethanes (THM) and other carcinogenic disinfection by-products (DBP). Long-term exposure to these compounds has been associated with an increased bladder cancer risk, although evidence is not conclusive yet. Objectives: -Assess the THM exposure in the study population, as a marker of total DBP level. -Estimate the bladder cancer risk associated to THM exposure. Methodology: (1) Meta-analysis of studies on chlorinated drinking water consumption and bladder cancer. We did a bibliographic search and selected studies evaluating individual long-term patterns of chlorinated drinking water consumption and bladder cancer. Six case-control studies were included (6.084 bladder cancer cases, 10.816 controls) and two cohort studies (124 cases) fulfilling the inclusion criteria. Odds ratios (OR) or relative risks (RR) plus 95% confidence intervals (95% CI) by sex and exposure category were extracted. We performed meta-analysis for the different exposure categories. (2) Pooled analysis of six case-control studies on bladder cancer and chlorination by-products, providing quantitative data about THM exposure levels and individual water consumption. Two studies were included from the USA, and one each from Canada, France, Italy and Finland. We extracted from the original databases exposure variables and covariates, combined using common definitions. The analysis included 2806 cases and 5254 controls. We calculated cumulative THM exposure (mg). OR and 95%CI were estimated using logistical regression adjusting by study and potential confounders. (3) Spanish case-control study of bladder cancer. Study subjects come from the 18 participating hospitals in Asturias, Alacant, Barcelona and Tenerife. THM exposure in the study population was assessed through personal interviews to 1226 cases and 1271 controls, THM measurements in 105 water samples from the study areas, and collection of retrospective THM levels through questionnaires to water companies and local authorities. OR and 95%CI were calculated using logistic regression adjusting by area and potential confounders. Analysis was limited to those subjects with exposure information =70% from the exposure window and subjects with unsatisfactory or questionable overall quality of interview were excluded. Results: (1) Ever consumption of chlorinated drinking water was associated with an increased bladder cancer risk in men (combined OR=1.4, 95%CI=1.1-1.9) and women (combined OR=1.2, 95%CI=0.7-1.8). (2) The adjusted odds ratio (OR) in men exposed >15 mg/l THM, compared to those with lower or no exposure, was 1.31 (95%CI=1.15-1.50). A monotonic increase in risk with increasing exposure was observed with an OR of 1.51 (95%CI=1.23-1.84) for exposure >1000 mg/l (p trend<0.001). Among women, THM exposure was not associated with risk. (3) The study areas with highest exposure were Alacant and Barcelona, with average THM levels in 1999 of 85.9 and 63.5 mg/l respectively. Tenerife showed the lowest levels (8.0 mg/l) and Asturias showed intermediate-low levels (22.3 mg/l). OR among men for an average THM ingestion exposure >35 mg/day related to 0 mg/day was 1.55, 95% CI= 1.02-2.35 (p trend=0.030). Those men swimming in the pool >630 hours in their lifetime had an OR of 2.08 (95% CI=1.06-4.09) in relation to those who had never swam. Main Conclusions: 1. Some Spanish areas are highly exposed to chlorination by-products, both currently and in the past. 2. The combined results strengthen the hypothesis that long-term exposure to THM at levels currently observed in many industrialized countries are associated with an increased bladder cancer risk. 3. Gender acts as an effect modifier, with a higher association observed among men 4. We find an association between swimming pool attendance and an increased bladder cancer risk. These results should be cautiously interpreted, since its the first study assessing these exposure routs and theres a need for specific studies to confirm these results.

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