Parental occupational exposure to pesticides, animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C).

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

Prenatal exposure to nitrate in drinking water and the risk of congenital anomalies.

BACKGROUND: Nitrate is a common water contaminant that has been associated with birth defects, although the evidence is limited. The purpose of this study was to examine whether maternal consumption of nitrate through drinking water is associated with an increased risk of congenital anomalies. METHODS: The study included a total of 348,250 singletons births from the state of Missouri between January 1, 2004 and December 31, 2008. Individual-level birth defect data and maternal and child characteristics were obtained from the Missouri birth defects registry and state vital statistics records. Outcomes were linked with county-specific monthly estimates of the nitrate concentration in finished water, based on data collected for compliance with the Safe Drinking Water Standard. Poisson models were fit to examine the association between nitrate exposure and birth defects. Average nitrate exposure during the first trimester and over 12 months prior to birth were modeled as continuous variables. Sensitivity analyses included restriction of the sample to counties with <20% and <10% private well usage to reduce exposure misclassification as well as limiting the analyses to residents of rural counties only to account for potential confounding by urbanicity. RESULTS: Estimated water concentrations of nitrate were generally low and below the Environmental Protection Agency's maximum contaminant level of 10 mg/L. Nitrate exposure was associated with a significantly increased risk of limb deficiencies (RR for 1 mg/L (RR1) = 1.26, 95% CI = 1.05, 1.51) in models without well restriction. Nitrate was also weakly associated with an increased risk of congenital heart defects (RR1 = 1.13, 95%CI = 0.93, 1.51) and neural tube defects (RR1 = 1.18, 95%CI = 0.93, 1.51) in models with well restriction (<10%). CONCLUSION: The positive associations found between nitrate exposure via drinking water and congenital abnormalities are largely consistent with some previous epidemiologic studies. The results of this study should be interpreted with caution given limitations in our ability to estimate exposures and the lack information on some risk factors for congenital abnormalities. Our findings may have serious policy implications given that exposure levels in our study were well below current EPA standards for nitrate in drinking water.

Arsenic in drinking water and adverse birth outcomes in Ohio.

BACKGROUND: Arsenic in drinking water has been associated with adverse reproductive outcomes in areas with high levels of naturally occurring arsenic. Less is known about the reproductive effects of arsenic at lower levels. OBJECTIVES: This research examined the association between low-level arsenic in drinking water and small for gestational age (SGA), term low birth weight (term LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth (VPTB) in the state of Ohio. METHODS: Exposure was defined as the mean annual arsenic concentration in drinking water in each county in Ohio from 2006 to 2008 using Safe Drinking Water Information System data. Birth outcomes were ascertained from the birth certificate records of 428,804 births in Ohio from the same time period. Multivariable generalized estimating equation logistic regression models were used to assess the relationship between arsenic and each birth outcome separately. Sensitivity analyses were performed to examine the roles of private well use and prenatal care utilization in these associations. RESULTS: Arsenic in drinking water was associated with increased odds of VLBW (AOR 1.14 per µg/L increase; 95% CI 1.04, 1.24) and PTB (AOR 1.10; 95% CI 1.06, 1.15) among singleton births in counties where <10% of the population used private wells. No significant association was observed between arsenic and SGA, or VPTB, but a suggestive association was observed between arsenic and term LBW. CONCLUSIONS: Arsenic in drinking water was positively associated with VLBW and PTB in a population where nearly all (>99%) of the population was exposed under the current maximum contaminant level of 10µg/L. Current regulatory standards may not be protective against reproductive effects of prenatal exposure to arsenic.

Livestock and poultry density and childhood cancer incidence in nine states in the USA.

BACKGROUND: Parental occupational and childhood exposures to farm animals have been positively associated with childhood brain tumors, whereas associations with childhood leukemia are equivocal. The developing immune system may be influenced by allergen, virus, or other exposures from animal sources, which may contribute to childhood cancer incidence. METHODS: Incident cancers (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], central nervous system [CNS], peripheral nervous system [PNS]) for children aged 0-4 diagnosed between 2003 and 2008 were obtained from nine National Cancer Institute Surveillance, Epidemiology and End Results (SEER) registries and were linked to U.S. Census of Agriculture data from 2002 and 2007 by county of diagnosis. Animal densities (animal units [AU]/km2; one animal unit is 1000 pounds of animal weight) were estimated for hogs, cattle, chickens (layers and broilers, separately), equine (horses, ponies, mules, burros, donkeys), goats, sheep, turkeys, and total animals. Animal density was examined in models as both continuous (AU per km2) and categorical variables (quartiles). Animal operation densities (per km2) by size of operation (cattle, hogs, chickens, sheep) were modeled continuously. Rate ratios and 95% confidence intervals were estimated using Poisson regression. RESULTS: We found positive associations between AML and broiler chicken densities (RRper 10AU/km2 = 1.14, 95% CI = 1.02-1.26). ALL rates increased with densities of hog operations (RRper operation/100km2 = 1.06, 95% CI = 1.02-1.11). PNS cancer rates were inversely associated with layer chicken density (RRper log of AU/km2 = 0.94, 95% CI = 0.89-0.99). No association was found between any cancer type and densities of cattle, equine, or goats. CONCLUSIONS: Although limited by the ecologic study design, some of our findings are novel and should be examined in epidemiological studies with individual level data.

Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study.

BACKGROUND: Inorganic arsenic is a lung, bladder, and skin carcinogen. One of the major sources of exposure to arsenic is through naturally contaminated drinking water. While positive associations have been observed between arsenic in drinking water and prostate cancer, few studies have explored this association in the United States. OBJECTIVES: To evaluate the association between inorganic arsenic concentrations in community water systems and prostate cancer incidence in Illinois using an ecologic study design. METHODS: Illinois Environmental Protection Agency data on arsenic concentrations in drinking water from community water systems throughout the state were linked with county-level prostate cancer incidence data from 2007 to 2011 from the Illinois State Cancer Registry. Incidence rates were indirectly standardized by age to calculate standardized incidence ratios (SIRs) for each county. A Poisson regression model was used to model the association between county-level SIRs and mean arsenic tertile (0.33-0.72, 0.73-1.60, and 1.61-16.23ppb), adjusting for potential confounders. RESULTS: For counties with mean arsenic levels in the second tertile, the SIR was 1.05 (95% CI: 0.96-1.16). For counties with mean arsenic levels in the third tertile, the SIR was 1.10 (95% CI: 1.03-1.19). There was a significant linear dose-response relationship observed between mean arsenic levels and prostate cancer incidence (p for trend=0.003). CONCLUSIONS: In this ecologic study, counties with higher mean arsenic levels in community water systems had significantly higher prostate cancer incidence. Individual-level studies of prostate cancer incidence and low-level arsenic exposure are needed.

A study update of mortality in workers at a phosphate fertilizer production facility.

OBJECTIVE: To evaluate the mortality experience among 3,199 workers employed 1951-1976 at a phosphate fertilizer production plant in central Florida with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Lung cancer and leukemia risks were further analyzed using conditional logistic regression. RESULTS: The mortality due to all-causes (SMR = 1.07, 95% confidence interval [CI] 1.02-1.13, observed deaths [n] = 1,473), all-cancers (SMR = 1.16, 95%CI 1.06-1.28, n = 431), and a priori outcomes of interests including lung cancer (SMR = 1.32, 95%CI = 1.13-1.53, n = 168) and leukemia (SMR = 1.74, 95%CI = 1.11-2.62, n = 23) were statistically significantly elevated. Regression modeling on employment duration or estimated radiation scores did not show exposure-response relation with lung cancer or leukemia mortality. CONCLUSION: SMR results showed increased lung cancer and leukemia mortality in a full cohort of the phosphate fertilizer production facility. There was, however, no exposure-response relation observed among cases and matched controls.

Ten-year cancer incidence in rescue/recovery workers and civilians exposed to the September 11, 2001 terrorist attacks on the World Trade Center.

BACKGROUND: Cancer incidence in exposed rescue/recovery workers (RRWs) and civilians (non-RRWs) was previously reported through 2008. METHODS: We studied occurrence of first primary cancer among World Trade Center Health Registry enrollees through 2011 using adjusted standardized incidence ratios (SIRs), and the WTC-exposure-cancer association, using Cox proportional hazards models. RESULTS: All-cancer SIR was 1.11 (95% confidence interval (CI) 1.03-1.20) in RRWs, and 1.08 (95% CI 1.02-1.15) in non-RRWs. Prostate cancer and skin melanoma were significantly elevated in both populations. Thyroid cancer was significantly elevated only in RRWs while breast cancer and non-Hodgkin's lymphoma were significantly elevated only in non-RRWs. There was a significant exposure dose-response for bladder cancer among RRWs, and for skin melanoma among non-RRWs. CONCLUSIONS: We observed excesses of total and specific cancers in both populations, although the strength of the evidence for causal relationships to WTC exposures is somewhat limited. Continued monitoring of this population is indicated. Am. J. Ind. Med. 59:709-721, 2016. © 2016 Wiley Periodicals, Inc.

Agricultural crop density and risk of childhood cancer in the midwestern United States: an ecologic study.

BACKGROUND: There is limited evidence for an association between agricultural pesticide exposure and certain types of childhood cancers. Numerous studies have evaluated exposure to pesticides and childhood cancer and found positive associations. However, few studies have examined the density of agricultural land use as a surrogate for residential exposure to agricultural pesticides and results are mixed. We examined the association of county level agricultural land use and the incidence of specific childhood cancers. METHODS: We linked county-level agricultural census data (2002 and 2007) and cancer incidence data for children ages 0-4 diagnosed between 2004 and 2008 from cancer registries in six Midwestern states. Crop density (percent of county area that was harvested) was estimated for total agricultural land, barley, dry beans, corn, hay, oats, sorghum, soybeans, sugar beets, and wheat. Rate ratios and 95% confidence intervals were estimated using generalized estimating equation Poisson regression models and were adjusted for race, sex, year of diagnosis, median household income, education, and population density. RESULTS: We found statistically significant exposure-response relationships for dry beans and total leukemias (RR per 1% increase in crop density = 1.09, 95% CI = 1.03-1.14) and acute lymphoid leukemias (ALL) (RR = 1.10, 95% CI = 1.04-1.16); oats and acute myeloid leukemias (AML) (RR = 2.03, 95% CI = 1.25, 3.28); and sugar beets and total leukemias (RR = 1.11, 95% CI = 1.04, 1.19) and ALL (RR = 1.11, 95% CI = 1.02, 1.21). State-level analyses revealed some additional positive associations for total leukemia and CNS tumors and differences among states for several crop density-cancer associations. However, some of these analyses were limited by low crop prevalence and low cancer incidence. CONCLUSIONS: Publicly available data sources not originally intended to be used for health research can be useful for generating hypotheses about environmental exposures and health outcomes. The associations observed in this study need to be confirmed by analytic epidemiologic studies using individual level exposure data and accounting for potential confounders that could not be taken into account in this ecologic study.

Respiratory disease mortality among US coal miners; results after 37 years of follow-up.

OBJECTIVES: To evaluate respiratory related mortality among underground coal miners after 37 years of follow-up. METHODS: Underlying cause of death for 9033 underground coal miners from 31 US mines enrolled between 1969 and 1971 was evaluated with life table analysis. Cox proportional hazards models were fitted to evaluate the exposure-response relationships between cumulative exposure to coal mine dust and respirable silica and mortality from pneumoconiosis, chronic obstructive pulmonary disease (COPD) and lung cancer. RESULTS: Excess mortality was observed for pneumoconiosis (SMR=79.70, 95% CI 72.1 to 87.67), COPD (SMR=1.11, 95% CI 0.99 to 1.24) and lung cancer (SMR=1.08; 95% CI 1.00 to 1.18). Coal mine dust exposure increased risk for mortality from pneumoconiosis and COPD. Mortality from COPD was significantly elevated among never [corrected] smokers and former smokers (HR=1.84, 95% CI 1.05 to 3.22; HRK=1.52, 95% CI 0.98 to 2.34, respectively) but not current smokers (HR=0.99, 95% CI 0.76 to 1.28). Respirable silica was positively associated with mortality from pneumoconiosis (HR=1.33, 95% CI 0.94 to 1.33) and COPD (HR=1.04, 95% CI 0.96 to 1.52) in models controlling for coal mine dust. We saw a significant relationship between coal mine dust exposure and lung cancer mortality (HR=1.70; 95% CI 1.02 to 2.83) but not with respirable silica (HR=1.05; 95% CI 0.90 to 1.23). In the most recent follow-up period (2000-2007) both exposures were positively associated with lung cancer mortality, coal mine dust significantly so. CONCLUSIONS: Our findings support previous studies showing that exposure to coal mine dust and respirable silica leads to increased mortality from malignant and non-malignant respiratory diseases even in the absence of smoking.

Multiple imputation for assessment of exposures to drinking water contaminants: evaluation with the Atrazine Monitoring Program.

BACKGROUND: Drinking water may contain pollutants that harm human health. The frequency of pollutant monitoring may occur quarterly, annually, or less frequently, depending upon the pollutant, the pollutant concentration, and community water system. However, birth and other health outcomes are associated with narrow time-windows of exposure. Infrequent monitoring impedes linkage between water quality and health outcomes for epidemiological analyses. OBJECTIVES: To evaluate the performance of multiple imputation to fill in water quality values between measurements in community water systems (CWSs). METHODS: The multiple imputation method was implemented in a simulated setting using data from the Atrazine Monitoring Program (AMP, 2006-2009 in five Midwestern states). Values were deleted from the AMP data to leave one measurement per month. Four patterns reflecting drinking water monitoring regulations were used to delete months of data in each CWS: three patterns were missing at random and one pattern was missing not at random. Synthetic health outcome data were created using a linear and a Poisson exposure-response relationship with five levels of hypothesized association, respectively. The multiple imputation method was evaluated by comparing the exposure-response relationships estimated based on multiply imputed data with the hypothesized association. RESULTS: The four patterns deleted 65-92% months of atrazine observations in AMP data. Even with these high rates of missing information, our procedure was able to recover most of the missing information when the synthetic health outcome was included for missing at random patterns and for missing not at random patterns with low-to-moderate exposure-response relationships. CONCLUSIONS: Multiple imputation appears to be an effective method for filling in water quality values between measurements.

A study of adverse birth outcomes and agricultural land use practices in Missouri.

BACKGROUND: Missouri is an agriculturally intensive state, primarily growing corn and soybeans with additional rice and cotton farming in some southeastern counties. Communities located in close proximity to pesticide-treated fields are known to have increased exposure to pesticides and may be at increased risk of adverse birth outcomes. The study aims were to assess the relationship between county-level measures of crop-specific agricultural production and adverse birth outcomes in Missouri and to evaluate the most appropriate statistical methodologies for doing so. METHODS: Potential associations between county level data on the densities of particular crops and low birth weight and preterm births were examined in Missouri between 2004-2006. Covariates considered as potential confounders and effect modifiers included gender, maternal race/ethnicity, maternal age at delivery, maternal smoking, access to prenatal care, quarter of birth, county median household income, and population density. These data were analyzed using both standard Poisson regression models as well as models allowing for temporal and spatial correlation of the data. RESULTS: There was no evidence of an association between corn, soybean, or wheat densities with low birth weight or preterm births. Significant positive associations between both rice and cotton density were observed with both low birth weight and preterm births. Model results were consistent using Poisson and alternative models accounting for spatial and temporal variability. CONCLUSIONS: The associations of rice and cotton with low birth weight and preterm births warrant further investigation. Study limitations include the ecological study design and limited available covariate information.

Community drinking water quality monitoring data: utility for public health research and practice.

CONTEXT: Environmental Public Health Tracking (EPHT) tracks the occurrence and magnitude of environmental hazards and associated adverse health effects over time. The EPHT program has formally expanded its scope to include finished drinking water quality. OBJECTIVES: Our objective was to describe the features, strengths, and limitations of using finished drinking water quality data from community water systems (CWSs) for EPHT applications, focusing on atrazine and nitrogen compounds in 8 Midwestern states. METHODS: Water quality data were acquired after meeting with state partners and reviewed and merged for analysis. RESULTS: Data and the coding of variables, particularly with respect to censored results (nondetects), were not standardized between states. Monitoring frequency varied between CWSs and between atrazine and nitrates, but this was in line with regulatory requirements. Cumulative distributions of all contaminants were not the same in all states (Peto-Prentice test P < .001). Atrazine results were highly censored in all states (76.0%-99.3%); higher concentrations were associated with increased measurement frequency and surface water as the CWS source water type. Nitrate results showed substantial state-to-state variability in censoring (20.5%-100%) and in associations between concentrations and the CWS source water type. CONCLUSIONS: Statistical analyses of these data are challenging due to high rates of censoring and uncertainty about the appropriateness of parametric assumptions for time-series data. Although monitoring frequency was consistent with regulations, the magnitude of time gaps coupled with uncertainty about CWS service areas may limit linkage with health outcome data.

Measuring dosage: a key factor when assessing the relationship between prenatal case management and birth outcomes.

To assess whether a measure of prenatal case management (PCM) dosage is more sensitive than a dichotomous PCM exposure measure when evaluating the effect of PCM on low birthweight (LBW) and preterm birth (PTB). We constructed a retrospective cohort study (N = 16,657) of Iowa Medicaid-insured women who had a singleton live birth from October 2005 to December 2006; 28 % of women received PCM. A PCM dosage measure was created to capture duration of enrollment, total time with a case manager, and intervention breadth. Propensity score (PS)-adjusted odds ratios (ORs), and 95 % confidence intervals (95 % CIs) were calculated to assess the risk of each outcome by PCM dosage and the dichotomous PCM exposure measure. PS-adjusted ORs of PTB were 0.88 (95 % CI 0.70-1.11), 0.58 (95 % CI 0.47-0.72), and 1.43 (95 % CI 1.23-1.67) for high, medium, and low PCM dosage, respectively. For LBW, the PS-adjusted ORs were 0.76 (95 % CI 0.57-1.00), 0.64 (95 % CI 0.50-0.82), and 1.36 (95 % CI 1.14-1.63), for high, medium, and low PCM dosage, respectively. The PCM dichotomous participation measure was not significantly associated with LBW (OR = 0.95, 95 % CI 0.82-1.09) or PTB (0.97, 95 % CI 0.87-1.10). The reference group in each analysis is No PCM. PCM was associated with a reduced risk of adverse pregnancy outcomes for Medicaid-insured women in Iowa. PCM dosage appeared to be a more sensitive measure than the dichotomous measure of PCM participation.

Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: a nested case-control study.

BACKGROUND: The US Food and Drug Administration has issued safety alerts about leukotriene receptor-modifying agents and suicidality/suicide, but because these were based on case reports, there is controversy about the association. OBJECTIVE: We conducted a nested case-control study to determine the association between leukotriene-modifying agents (LTMAs) and attempted suicide among asthmatic children and young adults. METHODS: Cases and control subjects were from a cohort of asthmatic patients aged 5 to 24 years who were new users of LTMAs or other asthma medications. Data were from an insurance claims database. Cases were defined as those with a suicide attempt (SA) occurring after exposure to asthma medication. Control subjects were persons at risk and were selected by using incidence density sampling in a 10:1 match. Conditional logistic regression was used to determine the association between LTMA exposure and the risk of attempted suicide adjusted for important covariates. RESULTS: We identified 344 cases and 3438 matched control subjects. Cases were more likely than control subjects to have risk factors for suicide. We found that current use of any LTMA was not associated with increased risk of an SA; in fact, the direction of effect was the opposite (adjusted odd ratio, 0.70; 95% CI, 0.36-1.39). CONCLUSION: In this analysis we found that use of LTMAs was not associated with an increased risk of SAs in children, adolescents, and young adults with asthma. Further research needs to be conducted to more fully understand the association between LTMAs and suicide, particularly in subpopulations.

Prenatal exposure to tap water containing nitrate and the risk of small-for-gestational-age: A nationwide register-based study of Danish births, 1991-2015.

BACKGROUND: Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. METHODS: We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991-2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. RESULTS: In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2-5 mg/L) (OR = 1.04, 95% CI: 1.03-1.06) and third category (>5-25 mg/L) (OR = 1.02, 95% CI: 1.00-1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01-1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). CONCLUSIONS: Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

OBJECTIVES: Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. METHODS: A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. RESULTS: Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. CONCLUSIONS: These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 µg/m(3) Cd.

Association between World Trade Center exposure and excess cancer risk.

CONTEXT: The terrorist attacks of September 11, 2001, resulted in the release of known and suspected carcinogens into the environment. There is public concern that exposures may have resulted in increased cancers. OBJECTIVE: To evaluate cancer incidence among persons enrolled in the World Trade Center Health Registry. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 55,778 New York State residents enrolled in the World Trade Center Health Registry in 2003-2004, including rescue/recovery workers (n = 21,850) and those not involved in rescue/recovery (n = 33,928), who were followed up from enrollment through December 31, 2008. Within-cohort comparisons using Cox proportional hazards models assessed the relationship between intensity of World Trade Center exposure and selected cancers. MAIN OUTCOME MEASURES: Cases were identified through linkage with 11 state cancer registries. Standardized incidence ratios (SIRs) adjusted for age, race/ethnicity, and sex were computed with 2003-2008 New York State rates as the reference, focusing on cancers diagnosed in 2007-2008 as being most likely to be related to exposure during September 11 and its aftermath. The total and site-specific incidence rate differences (RDs) per 100,000 person-years between the study population and the New York State population in 2007-2008 also were calculated. RESULTS: There were 1187 incident cancers diagnosed, with an accumulated 253,269 person-years (439 cancers among rescue/recovery workers and 748 among those not involved in rescue/recovery). The SIR for all cancer sites combined in 2007-2008 was not significantly elevated (SIR, 1.14 [95% CI, 0.99 to 1.30]; RD, 67 [95% CI, -6 to 126] per 100,000 person-years among rescue/recovery workers vs SIR, 0.92 [95% CI, 0.83 to 1.03]; RD, -45 [95% CI, -106 to 15] per 100,000 person-years among those not involved in rescue/recovery). Among rescue/recovery workers, the SIRs had significantly increased by 2007-2008 for 3 cancer sites and were 1.43 (95% CI, 1.11 to 1.82) for prostate cancer (n = 67; RD, 61 [95% CI, 20 to 91] per 100,000 person-years), 2.02 (95% CI, 1.07 to 3.45) for thyroid cancer (n = 13; RD, 16 [95% CI, 2 to 23] per 100,000 person-years), and 2.85 (95% CI, 1.15 to 5.88) for multiple myeloma (n = 7; RD, 11 [95% CI, 2 to 14] per 100,000 person-years). No increased incidence was observed in 2007-2008 among those not involved in rescue/recovery. Using within-cohort comparisons, the intensity of World Trade Center exposure was not significantly associated with cancer of the lung, prostate, thyroid, non-Hodgkin lymphoma, or hematological cancer in either group. CONCLUSIONS: Among persons enrolled in the World Trade Center Health Registry, there was an excess risk for prostate cancer, thyroid cancer, and myeloma in 2007-2008 compared with that for New York State residents; however, these findings were based on a small number of events and multiple comparisons. No significant associations were observed with intensity of World Trade Center exposures. Longer follow-up for typically long-latency cancers and attention to specific cancer sites are needed.

Prenatal exposure to nitrate from drinking water and the risk of preterm birth: A Danish nationwide cohort study.

Evidence is emerging that preterm birth (PTB, birth before 37 completed weeks of gestation), a risk factor for neonatal mortality and future morbidity, may be induced by maternal nitrate ( N O 3 - ) exposure from drinking water. The objective of this study is to assess the association between maternal exposure to nitrate and the risk of PTB in a nationwide study of liveborn singletons. Methods: We estimated maternal nitrate exposure from household tap water for 1,055,584 births in Denmark to Danish-born parents during 1991-2015 by linkage of individual home address(es) with nitrate concentrations from a national monitoring database. Nitrate exposure during pregnancy was modeled using four categories and continuously. Logistic models adjusted for sex, birth year, birth order, urbanicity, and maternal age, smoking, education, income, and employment, with generalized estimating equations were used to account for sibling clusters. Results: A total of 1,009,189 births were included, comprising 51,747 PTB. An increase in the risk of PTB was seen across categories of exposure (P < 0.001) with an odds ratio (OR) in the uppermost category (>25 mg/L nitrate) of 1.05 (95% confidence interval [CI] = 1.00, 1.10). Evidence of an exposure-response relationship was observed in models using continuous nitrate (OR = 1.01 [95% CI = 1.00, 1.03] per 10 mg/L nitrate). In sensitivity analyses, results were robust to the addition of variables for short inter-pregnancy interval (<1 year between births), maternal pre-pregnancy body mass index, paternal socioeconomic status and age, season of birth, and inclusion of post-term births. Results were virtually unchanged when the analysis was restricted to women exposed to less than the current European Union standard of 50 mg/L. Conclusion: We observed an increasing risk of PTB with increases in nitrate in household tap water. These findings add to a growing body of evidence of adverse effects from nitrate in drinking water at levels below current regulatory levels.