Dataset Information

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

ABSTRACT:

Background

By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants.

Objectives

In this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes.

Methods

We analyzed data from two large case-control studies-the New England Bladder Cancer Study (n/n=989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study (n/n=706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis.

Results

Of the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte-specific protein 1 (LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in meta-analysis. In the highest exposure category, we observed OR=1.66 (95% CI: 1.17, 2.34, p-trend=0.005) for those with the rs907611-GG genotype and p-interaction=0.02. No other genetic variants tested showed consistent evidence of interaction.

Discussion

We found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895.

SUBMITTER: Beane Freeman LE

PROVIDER: S-EPMC9088962 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

Beane Freeman Laura E LE Kogevinas Manolis M Cantor Kenneth P KP Villanueva Cristina M CM Prokunina-Olsson Ludmila L Florez-Vargas Oscar O Figueroa Jonine D JD Ward Mary H MH Koutros Stella S Baris Dalsu D Garcia-Closas Montserrat M Schwenn Molly M Johnson Allison A Serra Consol C Tardon Adonina A Garcia-Closas Reina R Carrato Alfredo A Malats Nuria N Karagas Margaret R MR Rothman Nathaniel N Silverman Debra T DT

Environmental health perspectives 20220510 5

<h4>Background</h4>By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants.<h4>Objectives</h4>In this stu ...[more]

PMID: 35536285

Similar Datasets

Project description:BackgroundDrinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive.ObjectiveWe conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns.MethodsWe included all births during 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and <5, 5-15, and >15μg TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.ResultsBased on 623,468 births and a prevalence of congenital malformation of ∼2 cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system (OR=1.82; 95% CI: 1.07, 3.12), urinary system (OR=2.06; 95% CI: 1.53, 2.78), genitals (OR=1.77; 95% CI: 1.38, 2.26), and limbs (OR=1.34; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite.DiscussionTTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. https://doi.org/10.1289/EHP9122.

Project description:BackgroundKnowledge about human exposure and health effects associated with non-routinely monitored disinfection by-products (DBPs) in drinking water is sparse.ObjectiveTo provide insights to estimate exposure to regulated and non-regulated DBPs in drinking water.MethodsWe collected tap water from homes (N = 42), bottled water (N = 10), filtered tap water with domestic activated carbon jars (N = 6) and reverse osmosis (N = 5), and urine (N = 39) samples of participants from Barcelona, Spain. We analyzed 11 haloacetic acids (HAAs), 4 trihalomethanes (THMs), 4 haloacetonitriles (HANs), 2 haloketones, chlorate, chlorite, and trichloronitromethane in water and HAAs in urine samples. Personal information on water intake and socio-demographics was ascertained in the study population (N = 39) through questionnaires. Statistical models were developed based on THMs as explanatory variables using multivariate linear regression and machine learning techniques to predict non-regulated DBPs.ResultsChlorate, THMs, HAAs, and HANs were quantified in 98-100% tap water samples with median concentration of 214, 42, 18, and 3.2 μg/L, respectively. Multivariate linear regression models had similar or higher goodness of fit (R2) compared to machine learning models. Multivariate linear models for dichloro-, trichloro-, and bromodichloroacetic acid, dichloroacetonitrile, bromochloroacetonitrile, dibromoacetonitrile, trichloropropnanone, and chlorite showed good predictive ability (R 2 = 0.8-0.9) as 80-90% of total variance could be explained by THM concentrations. Activated carbon filters reduced DBP concentrations to a variable extent (27-80%), and reverse osmosis reduced DBP concentrations ≥98%. Only chlorate was detected in bottled water samples (N = 3), with median = 13.0 µg/L. Creatinine-adjusted trichloroacetic acid was the most frequently detected HAA in urine samples (69.2%), and moderately correlated with estimated drinking water intake (r = 0.48).SignificanceFindings provide valuable insights for DBP exposure assessment in epidemiological studies. Validation of predictive models in a larger number of samples and replication in different settings is warranted.Impact statementOur study focused on assessing and describing the occurrence of several classes of DBPs in drinking water and developing exposure models of good predictive ability for non-regulated DBPs.

Dataset Information

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

Background

Objectives

Methods

Results

Discussion

Publications

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets