Disinfection Byproducts and Bladder Cancer

Villanueva, Cristina M.; Cantor, Kenneth P.; Cordier, Sylvaine; Jaakkola, Jouni J. K.; King, Will D.; Lynch, Charles F.; Porru, Stefano; Kogevinas, Manolis

doi:10.1097/01.ede.0000121380.02594.fc

Cited by 479 publications

(284 citation statements)

References 36 publications

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“…2,3 Experimental evidence has suggested that the mechanisms behind DBP carcinogenicity may partially be explained by epigenetic alterations that result from chronic cytotoxicity mediated by a mixture of oxidative metabolites release, reductive free radicals, and cell integrity disruption. 5,32 For non-genotoxic compounds, cycles of mitotic regeneration in response to cytotoxicity may produce cumulative epigenetic changes.…”

Section: Discussionmentioning

confidence: 99%

“…Trihalometanes (THMs) are one of the most abundant classes in chlorinated waters; in the past, Spain has shown high levels of THMs compared to Northern Europe. 1 Lifetime exposure to DBPs has been related to bladder cancer 2,3 and, possibly, colorectal cancer 4 in epidemiological studies. However, the mechanisms involved in these deleterious effects are not clear.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

et al. 2015

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Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a casecontrol study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels 85 mg/L vs. >85 mg/L (N D 68 and N D 70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 mg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Db| 0.05) located in 11 genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

et al. 2015

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“…Several epidemiological studies suggest a link between consumption of chlorinated drinking water and reproductive and developmental outcomes, such as increased spontaneous abortions and intrauterine growth retardation [10][11][12][13][14], and bladder and gastrointestinal tract cancers [15][16][17][18][19][20][21]. At present, which by-products in chlorinated drinking water could be responsible for increasing cancer risk in human beings is not well established, because the potential synergistic interactions of chlorinated by-products and their role in the molecular mechanisms of carcinogenesis are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons

Canistro

Melega

Ranieri

et al. 2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Epidemiological studies have shown an association between consumption of disinfected drinking water and adverse health outcomes. The chemicals used to disinfect water react with occurring organic matter and anthropogenic contaminants in the source water, resulting in the formation of disinfection byproducts (DBPs). The observations that some DBPs are carcinogenic in animal models have raised public concern over the possible adverse health effects for humans. Here, the modulation of liver cytochrome P450-linked monooxygenases (MFO) and the genotoxic effects in erythrocytes of Cyprinus carpio fish exposed in situ to surface drinking water in the presence of disinfectants, such as sodium hypochlorite (NaClO), chlorine dioxide (ClO 2 ) and peracetic acid (PAA), were investigated in winter and summer. A complex induction/suppression pattern of CYP-associated MFOs in winter was observed for all disinfectants. For example, a 3.4-to 15-fold increase was recorded of the CYP2B1/2-linked dealkylation of penthoxyresorufin with NaClO (10 days) and PAA (20 days). In contrast, ClO 2 generated the most notable inactivation, the CYP2E1-supported hydroxylation of p-nitrophenol being decreased up to 71% after 10 days' treatment. In summer, the degree of modulation was modest, with the exception of CYP3A1/2 and CYP1A1 supported MFOs (62% loss after 20 days PAA).The micronucleus (MN) induction in fish circulating erythrocytes was also analysed as an endpoint of genotoxic potential in the same fish population. Significant increases of MN induction were detected at the latest sampling time on fish exposed to surface water treated with chlorinate-disinfectants, both in winter (NaClO) and summer (NaClO and ClO 2 ), while no effect was observed in fish exposed to PAA-treated water.These results show that water disinfection may be responsible for harmful outcomes in terms of MFO perturbation and DNA damage; if extrapolated to humans, they ultimately offer a possible rationale for the increased urinary cancer risk recorded in regular drinking water consumers.

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“…Exposure to disinfection by-products (DBPs) has been associated with an increased risk of bladder cancer (Villanueva et al, 2004), and, while there might also be an association with adverse reproductive outcomes, the nature of this potential effect remains unclear (Nieuwenhuijsen et al, 2000a;Graves et al, 2001;Bove et al, 2002). Many of the epidemiological studies have relied on approximate measures of DBP exposure, such as concentration in the study subject's municipal water source, potentially resulting in substantial exposure misclassification.…”

Section: Introductionmentioning

confidence: 99%

Predictors of use and consumption of public drinking water among pregnant women

Forssén

Herring

Savitz

et al. 2006

J Expo Sci Environ Epidemiol

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Disinfection by-products (DBPs) in drinking water may be associated with adverse pregnancy outcomes. However, the results from previous epidemiological studies are not consistent, perhaps in part due to individual variation in water use and consumption. This study was performed to evaluate and describe demographic and behavioral characteristics as predictors of ingested water, showering, bathing, and swimming among pregnant women. Water use and consumption data were collected through telephone interviews with 2297 pregnant women from three geographical sites in the southern United States. The data were analyzed according to demographic, health, and behavioral variables expected to be predictors of water use and thus potential confounding factors relating water use to pregnancy outcome. The candidate predictors were evaluated using backward elimination in regression models. Demographic variables tended to be more strongly predictive of the use and consumption of water than health and behavior-related factors. NonHispanic white women drank 0.4 (95% confidence interval (CI) 0.2; 0.7) liters more cold tap water per day than Hispanic women and 0.3 (95% CI 0.1; 0.4) liters more than non-Hispanic black women. Non-Hispanic white women also reported drinking a higher proportion of filtered tap water, whereas Hispanic women replaced more of their tap water with bottled water. Lower socioeconomic groups reported spending a longer time showering and bathing, but were less likely to use swimming pools. The results of this study should help researchers to anticipate and better control for confounding and misclassification in studies of exposure to DBPs and pregnancy outcomes.

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Disinfection Byproducts and Bladder Cancer

Abstract: These findings strengthen the hypothesis that the risk of bladder cancer is increased with long-term exposure to disinfection byproducts at levels currently observed in many industrialized countries.

Cited by 479 publications

References 36 publications

DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons

Predictors of use and consumption of public drinking water among pregnant women

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