Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort.

BACKGROUND: Pollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied. OBJECTIVE: We described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators. METHODS: Participants' geocoded addresses at enrollment (1995-1996) were linked to CWS service area boundaries and monitoring data (N = 115,206, 92%); we computed average (1990-2015) concentrations of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE). We used generalized linear regression to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption at follow-up (2017-2019) were also described. RESULTS: Medians (interquartile ranges) of average concentrations of all contaminants were below regulatory limits: arsenic: 1.03 (0.54,1.71) µg/L, uranium: 3.48 (1.01,6.18) µg/L, GA: 2.21 (1.32,3.67) pCi/L, nitrate: 0.54 (0.20,1.97) mg/L, HAA5: 8.67 (2.98,14.70) µg/L, and TTHM: 12.86 (4.58,21.95) µg/L. Among those who lived within a CWS boundary and self-reported drinking water information (2017-2019), approximately 74% self-reported their water source as municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Spatially linked water source was largely consistent with self-reported source at follow-up (2017-2019). Relative to non-Hispanic white participants, average arsenic, uranium, GA, and nitrate concentrations were higher for Black, Hispanic and Native American participants. Relative to participants living in census block groups in the lowest socioeconomic status (SES) quartile, participants in higher SES quartiles had lower arsenic/uranium/GA/nitrate, and higher HAA5/TTHM. Non-metropolitan participants had higher arsenic/uranium/nitrate, and metropolitan participants had higher HAA5/TTHM. IMPACT: Though average water contaminant levels were mostly below regulatory limits in this large cohort of California women, we observed heterogeneity in exposures across sociodemographic subgroups and neighborhood characteristics. These data will be used to support future assessments of drinking water exposures and disease risk.

Residential proximity to toxic metal-emitting industrial sites and toenail metal concentrations in a United States-wide prospective cohort.

BACKGROUND: Industrial facilities across the United States (US) release millions of pounds of toxic chemicals, including metals. Exposure to toxic metals has been associated with adverse health outcomes, but there is limited evidence on the association between living near metal-releasing facilities and the body burden of emitted compounds. OBJECTIVE: To investigate the association between residential proximity to toxic metal-emitting industrial facilities and toenail metal concentrations and to evaluate whether associations differed by race. METHODS: In a sample of 1556 non-Hispanic Black (32.5%) and non-Hispanic White (67.5%) women from the Sister Study, we used the US Environmental Protection Agency Toxics Release Inventory to identify metal-emitting facilities within 3, 5, and 10 km of participants' baseline residences. We measured toenail concentrations (µg/g) of arsenic, cadmium, cobalt, chromium, and lead. Using multivariable linear regression, we examined associations between residential proximity to and emissions from metal-emitting facilities and toenail metal concentrations, stratifying by race. We explored modification of race-stratified associations by neighborhood deprivation, using the Area Deprivation Index (ADI). RESULTS: Black participants were more likely to reside within 3 km of chromium-releasing facilities and 5 and 10 km of all observed metal-emitting sites. Living near metal-releasing facilities was not associated with higher toenail metal concentrations overall. Among Black women, higher chromium emissions exposure was associated with higher toenail chromium levels (ßTertile3vs.non-exposed = 2.36 µg/g, 95% CI = 0.63, 4.10). An association with lead was observed among Black women residing in the most deprived areas (≥75th ADI percentile: ß = 3.08 µg/g, 95% CI = 1.46, 4.71). No associations were observed for White participants. CONCLUSIONS: Despite low exposure prevalence, our findings suggest that living near chromium- and lead-releasing facilities, especially at shorter distances, may be associated with higher corresponding toenail metal levels among Black women, particularly those residing in the most disadvantaged areas.

Residential proximity to dioxin-emitting facilities and risk of non-Hodgkin lymphoma in the NIH-AARP Diet and Health Study.

BACKGROUND: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are persistent organic pollutants emitted from industrial sources. Residential proximity to these emissions has been associated with risk of non-Hodgkin lymphoma (NHL) in a limited number of studies. METHODS: We evaluated associations between residential proximity to PCDD/F-emitting facilities and NHL in the NIH-AARP Diet and Health Study (N = 451,410), a prospective cohort enrolled in 1995-1996 in 6 states and 2 U.S. cities. We linked enrollment addresses with a U.S. Environmental Protection Agency database of 4,478 historical PCDD/F sources with estimated toxic equivalency quotient (TEQ) emissions. We evaluated associations between NHL and exposures during a historical period prior to enrollment (1980-1995) using an average emissions index, weighted by toxicity, distance, and wind direction (AEI-W [g TEQ/km2]) within 3-, 5- and 10 km of residences. We also evaluated proximity-only metrics indicating the presence/absence of one or more facilities within each distance, and metrics calculated separately for each facility type. We used Cox regression to estimate associations (hazard ratio, HR; 95 % confidence interval, 95 %CI) with NHL and major subtypes, adjusting for demographic, lifestyle, and dietary factors. RESULTS: A total of 6,467 incident cases of NHL were diagnosed through 2011. Participants with an AEI-W ≥ 95th percentile had elevated risk of NHL compared to those unexposed at 3 km (HR = 1.16; 95 %CI = 0.89-1.52; p-trend = 0.24), 5 km (HR = 1.20;95 %CI = 0.99-1.46;p-trend = 0.05) and 10 km (HR = 1.15; 95 %CI = 0.99-1.34; p-trend = 0.04). We found a positive association at 5 km with follicular lymphoma (HR≥95vs.0 = 1.62; 95 %CI = 0.98-2.67; p-trend = 0.05) and a suggestive association for diffuse large B-cell lymphoma (HR≥95vs.0 = 1.40; 95 %CI = 0.91-2.14; p-trend = 0.11). NHL risk was also associated with high emissions from coal-fired power plants within 10 km (HR≥95vs.0 = 1.42; 95 %CI = 1.09-1.84; p-trend = 0.05). CONCLUSIONS: Residential proximity to relatively high dioxin emissions from industrial sources may increase the risk of NHL and specific subtypes.

Long-term exposure to ambient fine particulate matter and risk of liver cancer in the NIH-AARP Diet and Health Study.

BACKGROUND: Fine particulate matter (PM2.5) exposure has been associated with liver cancer incidence and mortality in a limited number of studies. We sought to evaluate this relationship for the first time in a U.S. cohort with historical exposure assessment. METHODS: We used spatiotemporal prediction models to estimate annual average historical PM2.5 concentrations (1980-2015) at residential addresses of 499,729 participants in the NIH-AARP Diet and Health Study, a cohort in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, Georgia, and Detroit, Michigan) enrolled in 1995-1996 and followed up through 2017. We used a time-varying Cox model to estimate the association for liver cancer and the predominant histologic type, hepatocellular carcinoma (HCC), per 5 µg/m3 increase in estimated outdoor PM2.5 levels, incorporating a 5-year average, lagged 10 years prior to cancer diagnosis and adjusting for age, sex, race/ethnicity, education level and catchment state. We also evaluated PM2.5 interactions with hypothesized effect modifiers. RESULTS: We observed a non-significantly increased risk of liver cancer associated with estimated PM2.5 exposure (Hazard ratio [HR] = 1.05 [0.96-1.14], N = 1,625); associations were slightly stronger for HCC, (84 % of cases; HR = 1.08 [0.98-1.18]). Participants aged 70 or older at enrollment had an increased risk of liver cancer versus other age groups (HR = 1.50 [1.01-2.23]); p-interaction = 0.01) and risk was elevated among participants who did not exercise (HR = 1.81 [1.22-2.70]; p-interaction = 0.01). We found no evidence of effect modification by sex, smoking status, body mass index, diabetes status, or alcohol consumption (p-interaction > 0.05). CONCLUSIONS: Our findings in this large cohort suggest that residential ambient PM2.5 levels may be associated with liver cancer risk. Further exploration of the variation in associations by age and physical activity are important areas for future research.

Fine Particulate Matter, Noise Pollution, and Greenspace and Prostate Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Cohort.

BACKGROUND: Greenspace is hypothesized as being protective against cancer, whereas noise pollution and fine particulate matter (<2.5 µm in diameter, PM2.5) are both potential risk factors. Findings from recent studies of greenspace and PM2.5 with prostate cancer are not conclusive and the association between noise exposure and cancer has not been evaluated in a U.S. study. METHODS: We assessed PM2.5, noise, and greenspace exposure using spatiotemporal models and satellite-based estimates at enrollment addresses for N = 43,184 male participants of the prospective Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial cohort (enrolled 1994-2001). We used Cox regression models adjusted for age, race and ethnicity, study center, family history of prostate cancer, and Area Deprivation Index to estimate associations between ambient PM2.5 (µg/m3), greenspace (index range from -1 to 1), and noise pollution (loudest 10% of total existing sound, decibels) and incident prostate cancer risk through December 2017. RESULTS: A total of 6,327 cases of prostate cancer were diagnosed among male participants during follow-up. PM2.5 and noise exposures were moderately positively correlated (Spearman ρ = 0.46), and PM2.5 and greenspace were not correlated (ρ = 0.10); greenspace and noise were inversely correlated (ρ = -0.32). In single-pollutant and multipollutant models mutually adjusted for coexposures, we found no associations with prostate cancer risk. CONCLUSIONS: We did not find evidence that PM2.5, greenspace, and noise pollution were associated with prostate cancer risk in this large, geographically spread cohort. IMPACT: This study contributes to a small body of existing literature investigating these biologically plausible associations.

Sociodemographic inequities in the burden of carcinogenic industrial air emissions in the United States.

BACKGROUND: Industrial facilities are not located uniformly across communities in the United States, but how the burden of exposure to carcinogenic air emissions may vary across population characteristics is unclear. We evaluated differences in carcinogenic industrial pollution among major sociodemographic groups in the United States and Puerto Rico. METHODS: We evaluated cross-sectional associations of population characteristics including race and ethnicity, educational attainment, and poverty at the census tract level with point-source industrial emissions of 21 known human carcinogens using regulatory data from the US Environmental Protection Agency. Odds ratios and 95% confidence intervals comparing the highest emissions (tertile or quintile) to the referent group (zero emissions [ie, nonexposed]) for all sociodemographic characteristics were estimated using multinomial, population density-adjusted logistic regression models. RESULTS: In 2018, approximately 7.4 million people lived in census tracts with nearly 12 million pounds of carcinogenic air releases. The odds of tracts having the greatest burden of benzene, 1,3-butadiene, ethylene oxide, formaldehyde, trichloroethylene, and nickel emissions compared with nonexposed were 10%-20% higher for African American populations, whereas White populations were up to 18% less likely to live in tracts with the highest emissions. Among Hispanic and Latino populations, odds were 16%-21% higher for benzene, 1,3-butadiene, and ethylene oxide. Populations experiencing poverty or with less than high school education were associated with up to 51% higher burden, irrespective of race and ethnicity. CONCLUSIONS: Carcinogenic industrial emissions disproportionately impact African American and Hispanic and Latino populations and people with limited education or experiencing poverty thus representing a source of pollution that may contribute to observed cancer disparities.

Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California.

Rationale: Particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 µm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.

Ambient fine particulate matter and breast cancer incidence in a large prospective US cohort.

BACKGROUND: Fine particulate matter (PM2.5) has been inconsistently associated with breast cancer incidence, however, few studies have considered historic exposure when levels were higher. METHODS: Outdoor residential PM2.5 concentrations were estimated using a nationwide spatiotemporal model for women in the National Institutes of Health-AARP Diet and Health Study, a prospective cohort located in 6 states (California, Florida, Louisiana, New Jersey, North Carolina, and Pennsylvania) and 2 metropolitan areas (Atlanta, GA, and Detroit, MI) and enrolled in 1995-1996 (n = 196 905). Annual average PM2.5 concentrations were estimated for a 5-year historical period 10 years prior to enrollment (1980-1984). We used Cox regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between a 10 µg/m3 increase in PM2.5 and breast cancer incidence overall and by estrogen receptor status and catchment area. RESULTS: With follow-up of participants through 2017, a total of 15 870 breast cancer cases were identified. A 10 ug/m3 increase in PM2.5 was statistically significantly associated with overall breast cancer incidence (HR = 1.08, 95% CI = 1.02 to 1.13). The association was evident for estrogen receptor-positive (HR = 1.10, 95% CI = 1.04 to 1.17) but not estrogen receptor-negative tumors (HR = 0.97, 95% CI = 0.84 to 1.13; Pheterogeneity = .3). Overall breast cancer hazard ratios were more than 1 across the catchment areas, ranging from a hazard ratio of 1.26 (95% CI = 0.96 to 1.64) for North Carolina to a hazard ratio of 1.04 (95% CI = 0.68 to 1.57) for Louisiana (Pheterogeneity = .9). CONCLUSIONS: In this large US cohort with historical air pollutant exposure estimates, PM2.5 was associated with risk of estrogen receptor-positive breast cancer. State-specific estimates were imprecise but suggest that future work should consider region-specific associations and the potential contribution of PM2.5 chemical constituency in modifying the observed association.

Associations between per- and polyfluoroalkyl substances, liver function, and daily alcohol consumption in a sample of U.S. adults.

BACKGROUND AND AIM: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and in the serum of the U.S. POPULATION: We sought to evaluate the association of PFAS independently and jointly with alcohol intake on liver function biomarkers in a sample of the U.S. general population. METHODS: Using data from the National Health and Nutrition Examination Survey (2003-2016; N = 11,794), we examined the five most historically prevalent PFAS with >75% detection rates. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association between PFAS (quartiles and log-transformed continuous, ng/mL) and high levels (>95th percentile) of liver injury biomarkers using logistic regression models adjusted for key confounders. We evaluated interactions between PFAS and alcohol consumption and sex via stratified analyses and conducted sub-analyses adjusting for daily alcohol intake among those with available drinking history (N = 10,316). RESULT: Serum perfluorooctanoic acid (PFOA) was positively associated with high levels of alanine transferase (ALT) without monotonic trend (ORQ4vsQ1 = 1.45, CI: 0.99-2.12; p-trend = 0.18), and with increased aspartate transaminase when modeled continuously (OR = 1.15, CI: 1.02-1.30; p-trend = 0.03). Perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were both inversely associated with alkaline phosphatase while a trend was evident only for PFHxS (p = 0.02). A non-monotonic inverse association was observed with PFOA (p-trend = 0.10). The highest quartile of PFOS was associated with high total bilirubin (TB; ORQ4vsQ1 = 1.57, CI: 1.01-2.43, p-trend = 0.02). No significant associations were found between any PFAS and γ-glutamyl transpeptidase. We found no associations for perfluorodecanoic acid and perfluorononanoic acid. We observed some suggestive interactions with alcohol intake, particularly among heavy drinkers. CONCLUSION: Consistent with other studies, serum levels of PFOA, PFHxS and PFNA were positively associated with high levels of ALT, and we also observed weak positive associations between some PFAS and TB. Associations observed among heavy drinkers warrant additional evaluation.

Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a US cohort.

BACKGROUND: Ethylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers. METHODS: Using the US Environmental Protection Agency's Toxics Release Inventory, we estimated historical exposures for National Institutes of Health-AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction-adjusted average airborne emissions index (AEI=∑[lbs EtO/km2]). We estimated risk (hazard ratio [HR], 95% confidence interval [CI]) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945). RESULTS: We observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR[≤10vs>10] = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR[≤10vs>10] = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR[≤10vs>10] = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HR[Q4vs0] = 1.60, 95% CI = 0.98 to 2.61; HR[Q4vs0] = 1.28, 95% CI = 0.92 to 1.79; HR[Q4vs0] = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk. CONCLUSIONS: A novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.

Residential proximity to dioxin emissions and risk of breast cancer in the sister study cohort.

Some dioxins are carcinogenic, but few studies have investigated the relationship between ambient polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and risk of breast cancer. We evaluated associations between proximity-based residential exposure to industrial emissions of PCDD/F and breast cancer risk in a large U.S. cohort. Sister Study participants at enrollment (2003-2009) were followed for incident breast cancer through September 2018. After restricting to participants with ≥10 years of residential history prior to enrollment (n = 35,908), we generated 10-year distance- and toxic equivalency quotient (TEQ)-weighted average emissions indices (AEI [g TEQ/km2]) within 3, 5, or 10 km of participants' residences, overall and by facility type. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between AEI quartiles (vs. zero AEI) and risk of breast cancer [invasive or ductal carcinoma in situ]. There were 2670 incident breast cancer cases over 11 years (median) of follow-up. Breast cancer risk was increased for those in the highest quartile [Q] of AEI exposure within 3 km (HRQ4:1.18, 95% CI: 0.99,1.40, Ptrend = 0.03). The HR was higher for the 10-year AEI at 3 km from municipal solid waste facilities (HR ≥ median.vs.0:1.50, 95% CI: 0.98, 2.29; Ptrend = 0.07). Risk was higher among ever smokers (vs. never smokers) in the top quartile of the 3 km AEI (HRQ4:1.41, 95% CI:1.12,1.77, Ptrend = 0.003; Pinteraction = 0.03) and higher risk for ER negative tumors was suggested (HRQ4:1.47, 95% CI: 0.95, 2.28, Ptrend = 0.07, Pheterogeneity = 0.17). Our findings suggest that residential exposure to PCDD/F emissions may confer an increased risk of breast cancer.

Geographic Patterns in U.S. Lung Cancer Mortality and Cigarette Smoking.

BACKGROUND: Despite the success of smoking cessation campaigns, lung cancer remains the leading cause of cancer death in the U.S. Variations in smoking behavior and lung cancer mortality are evident by sex and region. METHODS: Applying geospatial methods to lung cancer mortality data from the National Vital Statistics System and county-level estimates of smoking prevalences from the NCI's Small Area Estimates of Cancer-Related Measures, we evaluated patterns in lung cancer mortality rates (2005-2018) in relation to patterns in ever cigarette smoking prevalences (1997-2003). RESULTS: Overall, ever smoking spatial patterns were generally associated with lung cancer mortality rates, which were elevated in the Appalachian region and lower in the West for both sexes. However, we also observed geographic variation in mortality rates that is not explained by smoking. Using Lee's L statistic for assessing bivariate spatial association, we identified counties where the ever smoking prevalence was low and lung cancer rates were high. We observed a significant cluster of counties (n = 25; P values ranging from 0.001 to 0.04) with low ever smoking prevalence and high mortality rates among females around the Mississippi River region south of St. Louis, Missouri and a similar and smaller cluster among males in Western Mississippi (n = 12; P values ranging from 0.002 to 0.03) that has not been previously described. CONCLUSIONS: Our analyses identified U.S. counties where factors other than smoking may be driving lung cancer mortality. IMPACT: These novel findings highlight areas where investigation of environmental and other risk factors for lung cancer is needed.

Outdoor light at night and risk of endometrial cancer in the NIH-AARP diet and health study.

PURPOSE: Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. METHODS: We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95% CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. RESULTS: We observed no association for endometrial cancer overall (HRQ1vsQ5 0.92; 95% CI 0.78-1.08; p trend = 0.67) or endometrioid adenocarcinoma (HRQ1vsQ5 1.01; 95% CI 0.82-1.24; p trend = 0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (p interactions = 0.52 and 0.50, respectively). CONCLUSION: Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by the inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.

Drinking water sources and water quality in a prospective agricultural cohort.

We describe drinking water sources and water quality for a large agricultural cohort. We used questionnaire data from the Agricultural Health Study (N = 89,655), a cohort of licensed pesticide applicators and their spouses in Iowa (IA) and North Carolina (NC), to ascertain drinking water source at enrollment (1993-1997). For users of public water supplies (PWS), we linked participants' geocoded addresses to contaminant monitoring data [five haloacetic acids (HAA5), total trihalomethanes (TTHM), and nitrate-nitrogen (NO3-N)]. We estimated private well nitrate levels using random forest models accounting for well depth, soil characteristics, nitrogen inputs, and other predictors. We assigned drinking water source for 84% (N = 74,919) of participants. Among these, 69% of IA and 75% of NC participants used private wells; 27% in IA and 21% in NC used PWS. Median PWS nitrate concentrations (NO3-N) were higher in IA [0.9 mg/L, interquartile range (IQR): 0.4-3.1 mg/L] than NC (0.1 mg/L, IQR: 0.1-0.2 mg/L), while median HAA5 and TTHM concentrations were higher in NC (HAA5: 11.9 µg/L, IQR: 5.5-33.4 µg/L; TTHM: 37.7 µg/L, IQR: 10.7-54.7 µg/L) than IA (HAA5: 5.0 µg/L, IQR: 3.7-10.7 µg/L; TTHM: 13.0 µg/L, IQR: 4.2-32.4 µg/L). Private well nitrate concentrations in IA (1.5 mg/L, IQR: 0.8-4.9 mg/L) and NC (1.9 mg/L, IQR: 1.4-2.5 mg/L) were higher than PWS. More private wells in IA (12%) exceeded 10 mg/L NO3-N (regulatory limit for PWS) than NC (<1%). Due to the proximity of their drinking water sources to farms, agricultural communities may be exposed to elevated nitrate levels.

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

BACKGROUND: Disinfection byproducts (DBPs) and N-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited. OBJECTIVES: We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort. METHODS: Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (NO3-N) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS >10y at enrollment (n=10,501; cases=261), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible ≥95th percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (>½ MCL; 40µg/L TTHM; 30µg/L HAA5; 5mg/L NO3-N). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for DBPs or NO3-N. We evaluated associations for low-grade (cases=99) vs. high-grade (cases=114) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation. RESULTS: Higher average concentrations of DBPs (95th percentile: TTHM ≥93µg/L, HAA5 ≥49µg/L) were associated with endometrial cancer risk (TTHM: HR95vsQ1=2.19, 95% CI: 1.41, 3.40; HAA5: HR95vsQ1=1.84, 95% CI: 1.19, 2.83; ptrend<0.01). Associations were similarly observed for women greater than median years of PWS use with levels >½ MCL, in comparison with zero years (TTHM: HR36+vs0y=1.61, 95% CI: 1.18, 2.21; HAA5: HR38+vs0y=1.85, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: HRQ4vsQ1=2.12, 95% CI: 1.17, 3.83; p-trend=0.008) than for high-grade tumors (TTHM: HRQ4vsQ1=1.40, 95% CI: 0.80, 2.44; p-trend=0.339), but differences were not statistically significant (p-heterogeneity=0.43). Associations with TTHM were stronger among ever HRT users than non-HRT users (p-interaction<0.01). We observed no associations with NO3-N in drinking water or diet. DISCUSSION: We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.

Emissions of dioxins and dioxin-like compounds and incidence of hepatocellular carcinoma in the United States.

Ambient dioxin exposure from industrial sources, excluding exposures from occupations and accidental releases/contamination, may be associated with risk of developing hepatocellular carcinoma (HCC). The objective of this study was to examine the association between county-level ambient dioxin air emissions from industrial sources and HCC risk in the US. We obtained information on 90,359 incident HCC cases diagnosed between 2000 and 2016 from population-based cancer registries across the US in the Surveillance, Epidemiology, and End Results (SEER) database. Dioxin emissions from 1987 to 2007 from a nationwide spatial database of historical dioxin-emitting facilities were linked to the SEER county of residence at diagnosis using a geographic information system (GIS). Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between county-level dioxin emissions and HCC rates adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level information on health conditions, lifestyle factors, and socioeconomic status. There was no association between dioxin emissions based on the number of dioxin-emitting facilities within a county or average annual emissions within a county and HCC risk. In analyses by facility type, there were positive associations between county-level dioxin emissions from coal-fired power plants (adjusted IRR 1.09, 95% CI 1.01-1.17), but not with the number of these facilities. Similarly, positive associations for industrial boilers and sewage sludge incinerators were evident, but not consistent across both exposure metrics. Future research should incorporate individual-level data to further explore the findings suggested by these ecologic analyses.

Evaluation of a commercial database to estimate residence histories in the los angeles ultrafines study.

BACKGROUND: Commercial databases can be used to identify participant addresses over time, but their quality and impact on environmental exposure assessment is uncertain. OBJECTIVE: To evaluate the performance of a commercial database to find residences and estimate environmental exposures for study participants. METHODS: We searched LexisNexis® for participant addresses in the Los Angeles Ultrafines Study, a prospective cohort of men and women aged 50-71 years. At enrollment (1995-1996) and follow-up (2004-2005), we evaluated attainment (address found for the corresponding time period) and match rates to survey addresses by participant characteristics. We compared geographically-referenced predictors and estimates of ultrafine particulate matter (UFP) exposure from a land use regression model using LexisNexis and survey addresses at enrollment. RESULTS: LexisNexis identified an address for 69% of participants at enrollment (N = 50,320) and 95% of participants at follow-up (N = 24,432). Attainment rate at enrollment modestly differed (≥5%) by age, smoking status, education, and residential mobility between surveys. The match rate at both survey periods was high (82-86%) and similar across characteristics. When using LexisNexis versus survey addresses, correlations were high for continuous values of UFP exposure and its predictors (rho = 0.86-0.92). SIGNIFICANCE: Time period and population characteristics influenced the attainment of addresses from a commercial database, but accuracy and subsequent estimation of specific air pollution exposures were high in our older study population.

Spatial Heterogeneity in Positional Errors: A Comparison of Two Residential Geocoding Efforts in the Agricultural Health Study.

Geocoding is a powerful tool for environmental exposure assessments that rely on spatial databases. Geocoding processes, locators, and reference datasets have improved over time; however, improvements have not been well-characterized. Enrollment addresses for the Agricultural Health Study, a cohort of pesticide applicators and their spouses in Iowa (IA) and North Carolina (NC), were geocoded in 2012-2016 and then again in 2019. We calculated distances between geocodes in the two periods. For a subset, we computed positional errors using "gold standard" rooftop coordinates (IA; N = 3566) or Global Positioning Systems (GPS) (IA and NC; N = 1258) and compared errors between periods. We used linear regression to model the change in positional error between time periods (improvement) by rural status and population density, and we used spatial relative risk functions to identify areas with significant improvement. Median improvement between time periods in IA was 41 m (interquartile range, IQR: -2 to 168) and 9 m (IQR: -80 to 133) based on rooftop coordinates and GPS, respectively. Median improvement in NC was 42 m (IQR: -1 to 109 m) based on GPS. Positional error was greater in rural and low-density areas compared to in towns and more densely populated areas. Areas of significant improvement in accuracy were identified and mapped across both states. Our findings underscore the importance of evaluating determinants and spatial distributions of errors in geocodes used in environmental epidemiology studies.

Impact of residential mobility on estimated environmental exposures in a prospective cohort of older women.

Longitudinal studies of environmental hazards often rely on exposure estimated at the participant's enrollment residence. This could lead to exposure misclassification if participants move over time. METHODS: We evaluated residential mobility in the Iowa Women's Health Study (age 55-69 years) over 19 years of follow-up (1986-2004). We assessed several environmental exposures of varying spatial scales at enrollment and follow-up addresses. Exposures included average nitrate concentrations in public water supplies, percent of agricultural land (row crops and pasture/hay) within 750 m, and the presence of concentrated animal feeding operations within 5 km. In comparison to gold standard duration-based exposures averaged across all residences, we evaluated the sensitivity and specificity of exposure metrics and attenuation bias for a hypothetical nested case-control study of cancer, which assumed participants did not move from their enrollment residence. RESULTS: Among 41,650 participants, 32% moved at least once during follow-up. Mobility was predicted by working outside the home, being a former/current smoker, having a higher education level, using a public drinking water supply, and town size of previous residence. Compared with duration-based exposures, the sensitivity and specificity of exposures at enrollment ranged from 94% to 99% and 97% to 99%, respectively. A hypothetical true odds ratio of 2.0 was attenuated 8% for nitrate, 9%-10% for agricultural land, and 6% for concentrated animal feeding operation exposures. CONCLUSIONS: Overall, we found low rates of mobility and mobility-related exposure misclassification in the Iowa Women's Health Study. Misclassification and attenuation of hypothetical risk estimates differed by spatial variability and exposure prevalence.