Article

Female Breast Cancer and Trihalomethane Levels in Drinking Water in North Carolina

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Abstract

Some studies indicate that chlorination by-products in drinking water may contribute slightly to breast cancer risk. This ecologic study describes the association between total trihalomethane levels in publicly supplied water and the incidence of female invasive breast cancer. We included 71 North Carolina water suppliers serving at least 10,000 customers in the summer of 1995 as the units of analysis. We estimated incidence rates using 6,462 cases who were either white or black and between 35 and 84 years old and were linked by zip codes to the water supplier. We treated ecologic measurements of age, income, education, urban status, and race as potential confounders. Total trihalomethane levels were not associated materially with breast cancer risk, adjusting for potential confounders. The rate ratio for 80.0 parts per billion (ppb) or more vs less than 40.0 ppb total trihalomethanes was 1.1 [95% confidence interval (CI) = 0.9-1.2]. When stratified by race, the observed association for the aforementioned total trihalomethane category was not very different in black women (rate ratio = 1.2; 95% CI = 0.8-1.8) than in white women (rate ratio = 1.1; 95% CI = 0.9-1.3). These ecologic data are compatible with trihalomethanes in drinking water being either unrelated or weakly related to breast cancer risk.

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... Environmental pollutants encompass a variety of characteristics but here we focus at residential pollutants. Two studies [45,46] looked at residential pollutants, specifically residential magnetic field exposure and trihalomethane levels in public drinking water. The results showed that neither, magnetic field exposure or trihalomethane levels, had effects on breast cancer incidence in African American women (OR = 1.02; 95% CI = 0.89, 1.16) and (OR = 1.2; 95% CI = 0.8, 1.8), respectively. ...
... The results showed that neither, magnetic field exposure or trihalomethane levels, had effects on breast cancer incidence in African American women (OR = 1.02; 95% CI = 0.89, 1.16) and (OR = 1.2; 95% CI = 0.8, 1.8), respectively. The odds ratio of trihalomethane levels was at the highest parts per billion (ppb) ≥ 80; however, there was still little or no effect shown on breast cancer incidence [46]. Each study examined the exposure at least 8 years after the pollutants were exposed. ...
... The distribution of qualification differed substantially across criteria. All 18 studies included in the review clearly described their research question and objective, had similarity among populations and inclusion and exclusion criteria, clearly defined neighborhood and residential factors, and confounded variables in their analysis [18,20,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. In contrast, all but two studies [19,38] clearly defined the study population, in addition, only one study [45] blinded assessors for outcome variables. ...
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Background: Breast cancer was included as a priority in the Chilean health reform, providing universal and guaranteed access to diagnosis and treatment to all women aged 15 years or more. Aim: To analyze the incidence, staging and survival of breast cancer in a cohort of women. Material and Methods: Retrospective analysis of medical records of women operated for breast cancer between 1994 and 2005 in two public hospitals of Metropolitan Santiago. Incidence rates were calculated using statistical information provided by the Ministry of Health. Results: The clinical records of 1.485 women aged 18 to 99 years (median 55 years), were analyzed. The number of lesions detected in early stages (T1 N0), increased progressively over time. The number of lesions in advanced stages was constant along time, but its proportion decreased progressively. The overall fifteen years survival of operated women was 64%. Survival was significantly better among women without lymph node involvement. The incidence rates of breast cancer increased steadily during the study period. Mortality slightly increased during the nineties but is decreasing during the present decade, reaching a rate of 12.2 per 100.000 women during 2005. Conclussion: In this series of patients, the diagnosis of breast cancer in early stages increased in the last decade, resulting in better survival rates.
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This article describes the disinfection by-product (DBP) characterization portion of a series of experiments designed for comprehensive chemical and toxicological evaluation of two drinking-water concentrates containing highly complex mixtures of DBPs. This project, called the Four Lab Study, involved the participation of scientists from four laboratories and centers of the U.S. Environmental Protection Agency (EPA) Office of Research and Development, along with collaborators from the water industry and academia, and addressed toxicologic effects of complex DBP mixtures, with an emphasis on reproductive and developmental effects that are associated with DBP exposures in epidemiologic studies. Complex mixtures of DBPs from two different disinfection schemes (chlorination and ozonation/postchlorination) were concentrated successfully, while maintaining a water matrix suitable for animal studies. An array of chlorinated/brominated/iodinated DBPs was created. The DBPs were relatively stable over the course of the animal experiments, and a significant portion of the halogenated DBPs formed in the drinking water was accounted for through a comprehensive qualitative and quantitative identification approach. DBPs quantified included priority DBPs that are not regulated but have been predicted to produce adverse health effects, as well as those currently regulated in the United States and those targeted during implementation of the Information Collection Rule. New by-products were also reported for the first time. These included previously undetected and unreported bromo- and chloroacids, iodinated compounds, bromo- and iodophenols, and bromoalkyltins.
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Background: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. Objectives: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. Methods: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. Results: Mean adult-lifetime residential levels ranged from 0.8 to 145.7μg/L for TTHM (median=30.8), from 0.2 to 62.4μg/L for chloroform (median=19.7) and from 0.3 to 126.0μg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24μg/L) vs. lowest (<8μg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31μg/L vs. <6μg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48μg/L vs. <22μg/L). Conclusions: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.
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Chemical disinfection of drinking water is a major public health triumph of the 20th century, resulting in significant decreases in morbidity and mortality from waterborne diseases. Disinfection by-products (DBP) are chemicals formed by the reaction of oxidizing disinfectants with inorganic and organic materials in the source water. To address potential health concerns that cannot be answered directly by toxicological research on individual DBPs or defined DBP mixtures, scientists residing within the various organizations of the U.S. Environmental Protection Agency's Office of Research and Development (the National Health and Environmental Effects Research Laboratory, the National Risk Management Research Laboratory, the National Exposure Research Laboratory, and the National Center for Environmental Assessment) engaged in joint investigation of environmentally realistic complex mixtures of DBP. Research on complex mixtures of DBP is motivated by three factors: (a) DBP exposure is ubiquitous to all segments of the population; (b) some positive epidemiologic studies are suggestive of potential developmental, reproductive, or carcinogenic health effects in humans exposed to DBP; and (c) significant amounts of the material that makes up the total organic halide portion of the DBP have not been identified. The goal of the Integrated Disinfection Byproducts Mixtures Research Project (the 4Lab Study) is provision of sound, defensible, experimental data on environmentally relevant mixtures of DBP and an improved estimation of the potential health risks associated with exposure to the mixtures of DBP formed during disinfection of drinking water. A phased research plan was developed and implemented. The present series of articles provides the results from the first series of experiments.
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Previous epidemiological studies in Massachusetts have reported a risk of adverse health outcomes in relation to disinfection by-product (DBP) exposures. Measurement error due to the use of indirect exposure surrogates can lead to misclassification bias in epidemiological studies; therefore, it is important to characterize exposure variability in these populations to assess the potential for exposure misclassification. We used 19,944 trihalomethane (THM) samples and 9291 haloacetic acid (HAA) samples collected in 201 public water systems (PWSs) in Massachusetts to examine temporal variability under different drinking water sources and disinfection types. Annual and seasonal variability was also examined in 46 PWSs with complete quarterly THM4 (i.e., the sum of 4 individual THMs) data from 1995 to 2004 and 19 PWSs with complete HAA5 (i.e., the sum of 5 individual HAAs) data from 2001 to 2004. The quarterly ratio of THM4 and HAA5 and correlations between THM4, HAA5 and individual DBP species were examined to determine the adequacy of using different exposure surrogates in epidemiological studies. Individual PWSs were used to examine monthly variability in relation to quarterly averages. Based on all available matched samples (n=9003) from 1995 to 2004 data, we found a correlation of 0.52 for THM4 and HAA5. The correlation was stronger among the 62 ground water systems (r(s)=0.62) compared to the 81 surface water (r(s)=0.45) and 40 mixed water (r(s)=0.39) systems. Mean THM4 levels were fairly stable over the 10-year study period for 46 PWSs including 39 PWSs that did not change disinfection. Large reductions (∼40 μg/L) in mean THM4 data were found among seven systems that switched from chlorination to alternative disinfectants. As expected, the highest mean THM4 values were detected for Quarter 3, while the lowest values were found in Quarter 1. The highest HAA5 values were detected in Quarters 2 and 3 and the lowest was found in Quarter 4. Data from four systems showed mean differences up to 66 μg/L (67% change) in successive months and by 46 μg/L compared to quarterly mean concentrations. Although longer-term disinfection by-product temporality may be minimal in this study population, the use of monthly average concentrations for exposure assessment may be needed for some PWSs to minimize misclassification of narrow critical periods of exposure in epidemiological studies.
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The relationship between chlorination by-products (CBPs) in drinking water and human health outcomes has been investigated in many epidemiological studies. In these studies, population exposure assessment to CBPs in drinking water is generally based on available CBP data (e.g., from regulatory monitoring, sampling campaigns specific to study area). Since trihalomethanes (THMs) and haloacetic acids (HAAs) are the most documented CBP classes in drinking water, they are generally used as indicators of CBP exposure. In this paper, different approaches to spatially assign available THM and HAA concentrations in drinking water for population exposure assessment purposes are investigated. Six approaches integrating different considerations for spatial variability of CBP occurrence within different distribution systems are compared. For this purpose, a robust CBP database (i.e., high number of sampling locations selected according to system characteristics) corresponding to nine distribution systems was generated. The results demonstrate the high impact of the structure of the distribution system (e.g., presence of intermediary water infrastructures such as re-chlorination stations or reservoirs) and the spatial variability of CBPs in the assigned levels for exposure assessment. Recommendations for improving the exposure assessment to CBPs in epidemiological studies using available CBP data from water utilities are also presented.
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Exposure to total trihalomethanes in drinking water has been associated with several adverse birth outcomes relating to fetal growth and prematurity. We carried out a systematic review and meta-analysis of epidemiologic studies featuring original peer-reviewed data on the association of total trihalomethane exposure and health outcomes related to fetal growth and prematurity. A comprehensive literature search yielded 37 studies, 15 of which were selected for the extraction of relative risks relating adverse birth outcomes to trihalomethane exposure. Sufficient data were available for meta-analyses to be carried out for 4 adverse birth outcomes: low birth weight (LBW), term low birth weight (term LBW), preterm delivery, and small for gestational age (SGA) (including intra uterine growth retardation). We found little or no evidence for associations between third trimester trihalomethane exposure and LBW (odds ratio per 10 microg total trihalomethane/L = 1.00 [95% confidence interval = 0.97-1.03]), term LBW (1.03 [0.93-1.15]), or preterm delivery (0.99 [0.98-1.00]), but some evidence for SGA (1.01 [1.00-1.02]). There was little or no evidence for associations between total trihalomethane concentration and adverse birth outcomes relating to fetal growth and prematurity, with the possible exception of SGA. We discuss these findings and the uncertainties-relating particularly to exposure-that may have affected them.
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Reactive chemicals have been used to disinfect drinking waters for over a century. In the 1970s, it was first observed that the reaction of these chemicals with the natural organic matter (NOM) in source waters results in the production of variable, complex mixtures of disinfection by-products (DBP). Because limited toxicological and epidemiological data are available to assess potential human health risks from complex DBP mixture exposures, methods are needed to determine when health effects data on a specific DBP mixture may be used as a surrogate for evaluating another environmental DBP mixture of interest. Before risk assessors attempt such efforts, a set of criteria needs to be in place to determine whether two or more DBP mixtures are similar in composition and toxicological potential. This study broadly characterizes the chemical and toxicological measures that may be used to evaluate similarities among DBP mixtures. Variables are discussed that affect qualitative and quantitative shifts in the types of DBP that are formed, including disinfectants used, their reactions with NOM and with bromide/iodide, pH, temperature, time, and changes in the water distribution system. The known toxicological activities of DBP mixtures and important single DBPs are also presented in light of their potential for producing similar toxicity. While DBP exposures are associated with a number of health effects, this study focuses on (1) mutagenic activity of DBP mixtures, (2) DBP cancer epidemiology, and (3) toxicology studies to evaluate similarity among DBP mixtures. Data suggest that further chemical characterization of DBP mixtures and more systematic study of DBP toxicology will improve the quality and usefulness of similarity criteria.
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By international standards, water supplies in Perth, Western Australia, contain high trihalomethane (THM) levels, particularly the brominated forms. Geographic variability in these levels provided an opportunity to examine cross-city spatial relationships between THM exposure and rates of birth defects (BDs). Our goal was to examine BD rates by exposure to THMs with a highly brominated fraction in metropolitan locations in Perth, Western Australia. We collected water samples from 47 separate locations and analyzed them for total and individual THM concentrations (micrograms per liter), including separation into brominated forms. We classified collection areas by total THM (TTHM) concentration: low (< 60 microg/L), medium (> 60 to < 130 microg/L), and high (> or = 130 microg/L). We also obtained deidentified registry-based data on total births and BDs (2000-2004 inclusive) from post codes corresponding to water sample collection sites and used binomial logistic regression to compare the frequency of BDs aggregately and separately for the TTHM exposure groups, adjusting for maternal age and socioeconomic status. Total THMs ranged from 36 to 190 microg/L. A high proportion of the THMs were brominated (on average, 92%). Women living in high-TTHM areas showed an increased risk of any BD [odds ratio (OR) = 1.22; 95% confidence interval (CI), 1.01-1.48] and for the major category of any cardiovascular BD (OR = 1.62; 95% CI, 1.04-2.51), compared with women living in low-TTHM areas. Brominated forms constituted the significant fraction of THMs in all areas. Small but statistically significant increases in risks of BDs were associated with residence in areas with high THMs.
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Laboratory evidence suggests tap water disinfection by-products (DBPs) could have an effect very early in pregnancy, typically before clinical detectability. Undetected early losses would be expected to increase the reported number of cycles to clinical pregnancy. We investigated the association between specific DBPs (trihalomethanes, haloacetic acids, brominated-trihalomethanes, brominated-haloacetic acids, total organic halides, and bromodichloromethane) and time to pregnancy among women who enrolled in a study of drinking water and reproductive outcomes. We quantified exposure to DBPs through concentrations in tap water, quantity ingested through drinking, quantity inhaled or absorbed while showering or bathing, and total integrated exposure. The effect of DBPs on time to pregnancy was estimated using a discrete time hazard model. Overall, we found no evidence of an increased time to pregnancy among women who were exposed to higher levels of DBPs. A modestly decreased time to pregnancy (ie, increased fecundability) was seen among those exposed to the highest level of ingested DBPs, but not for tap water concentration, the amount absorbed while showering or bathing, or the integrated exposure. Our findings extend those of a recently published study suggesting a lack of association between DBPs and pregnancy loss.
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The 88 counties of Ohio were classified as either ground water or surface water counties based on the source of the drinking water used by a majority of the county residents included in the 1963 U.S. Public Health Service Inventory of Municipal Water Facilities. Average cancer mortality rates for surface and ground water counties were compared using analysis of covariance. Mortality rates for stomach, bladder, and all malignant neoplasms were higher for white males in counties served by surface water supplies than in counties served by ground water supplies. Mortality rates for stomach neoplasms were higher for white females in surface water counties. These differences in mortality rates were not attributable to other factors known to be associated with cancer death rates including urbanization, median income, population size, manufacturing activity, and agriculture-forestry-fishery activity.
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Individual epidemiological investigations into the association between chlorination by-products in drinking water and cancer have been suggestive but inconclusive. Enough studies exist to provide the basis for a meaningful meta-analysis. An extensive literature search was performed to identify pertinent case-control studies and cohort studies. Consumption of chlorinated water, surface water, or water with high levels of chloroform was used as a surrogate for exposure to chlorination by-products. Relative risk estimates were abstracted from the individual studies and pooled. A simple meta-analysis of all cancer sites yielded a relative risk estimate for exposure to chlorination by-products of 1.15 (95% CI: 1.09, 1.20). Pooled relative risk estimates for organ-specific neoplasms were 1.21 (95% CI: 1.09, 1.34) for bladder cancer and 1.38 (95% CI: 1.01, 1.87) for rectal cancer. When studies that adjusted for potential confounders were pooled separately, estimates of relative risks did not change substantially. The results of this meta-analysis suggest a positive association between consumption of chlorination by-products in drinking water and bladder and rectal cancer in humans.
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The practice of chlorination in preference to other methods of disinfection should not be phased out until there is stronger epidemiological and clinical evidence to support the charge that it produces serious health risks, and until the potential health effects of substitute disinfectants are carefully explored.
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A modification of the iterated reweighted least squares scheme of D. A. Williams conveniently accommodates extra-Poisson variation when fitting log-linear models to tables of frequencies or rates. The method is applied to the analysis of cancer death rates by age and birth cohort and to testing for mutagenic effects in a standard bioassay. A set of macros for implementing the two procedures with GLIM is given.
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Multivariant regression analysis indicates a statistically significant relation between cancer mortality rates in Louisiana and drinking water obtained from the Missippi River. This is true for total cancer, cancer of the urinary organs, and cancer of the gastrointestinal tract.
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Our review of the literature on the importance of inhalation and dermal exposures to volatile organic compounds in household water relative to ingestion exposures sought to answer two questions. First, how well do the inhalation and dermal doses predicted by simple models, complex simulations, and measurements agree with one another? And second, what are the implications for the cancer risk from chloroform in household water? The literature yields a coherent and credible range of dose estimates: the ratio of lifetime inhalation dose to lifetime ingestion dose is probably in the range of approximately 0.6 to approximately 1.5, but may be as high as approximately 5.7; and the ratio of lifetime dermal dose to lifetime ingestion dose is probably about approximately 0.3, but may be as high as approximately 1.8. However, because the U.S. Environmental Protection Agency's (EPA's) Cancer Potency Factor (CPF) for inhalation of chloroform is much higher than the CPF for ingestion, the ratios of incremental lifetime cancer risk from inhalation of chloroform to risk from ingestion are much larger than the corresponding ratios for dose. The incremental lifetime cancer risk from chloroform by all three pathways is probably approximately 9 to approximately 21 times the ingestion risk and may be as much as approximately 79 times the ingestion risk. As the EPA reviews the drinking water standard for total trihalomethanes, it is essential that the Agency take account of all exposure pathways in estimating cancer risk.
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In 1984 the North Carolina Medical Society's House of Delegates adopted Report S, which called for the North Carolina Legislature to fund a statewide cancer incident reporting system. The Cancer Committee continues to be advisory to the Division of Adult Health. A subcommittee of the Cancer Committee advises the Central Cancer Registry.
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Greenland S (Division of Epidemiology, UCLA School of Public Health, Los Angeles, California 90024, USA) and Morgenstern H. Ecological bias, confounding, and effect modification. International Journal of Epidemiology 1989, 18: 269–274. Ecological bias is sometimes attributed to confounding by the group variable (ie the variable used to define the ecological groups), or to risk factors associated with the group variable. We show that the group variable need not be a confounder (in the strict epidemiological sense) for ecological bias to occur: effect modification can lead to profound ecological bias, whether or not the group variable or the effect modifier are independent risk factors. Furthermore, an extraneous risk factor need not be associated with the study variable at the individual level in order to produce ecological bias. Thus the conditions for the production of ecological bias by a covariate are much broader than the conditions for the production of individual-level confounding by a covariate. We also show that standardization or ecological control of variables responsible for ecological bias are generally insufficient to remove such bias.
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Age-adjusted, sex-specific cancer incidence rates for the years 1969-1978 were determined for municipalities in Iowa having a population of 1000 or over and public water supply that had remained stable for a minimum of 14 years. The incidence rates for the municipalities were examined according to major source of water supply (surface or ground) and depth of well. As municipality size increased, incidence rates increased for cancer of the lung among males and females. A slight gradient of increasing cancer incidence was seen for cancer of the bladder among males and females. When stratified for population size, incidence rates for cancers of the lung and rectum among males and females were higher for municipalities on surface water compared with those on ground sources. Incidence rates for cancer of the prostate rose as well depth increased, while a trend was seen toward decreasing incidence rates for cancer of the colon among females as well depth increased. When time trends were examined, an increase in cancer rates over time was seen for several cancer sites, with the increase most noticeable in municipalities supplied by surface water or shallow wells. These results are not always consistent with the hypothesis of an association between cancer and chlorinated water.