BACKGROUND: Drinking water at US Marine Corps Base Camp Lejeune, North Carolina, was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. METHODS: A cohort cancer incidence study was conducted of Marines/Navy personnel who began service and were stationed at Camp Lejeune (N = 154,821) or Camp Pendleton, California (N = 163,484) between 1975 and 1985 and civilian workers employed at Camp Lejeune (N = 6,494) or Camp Pendleton (N = 5,797) between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Individual-level information on primary invasive cancers and in situ bladder cancer diagnosed between 1996 and 2017 was obtained from 54 US cancer registries. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing cancer incidence between the Camp Lejeune and Camp Pendleton cohorts, adjusted for sex, race, education, and rank (or blue-collar work), with age as the time variable. Precision of aHRs was evaluated using the 95% confidence interval (CI) ratio (CIR). RESULTS: Cancers among Camp Lejeune Marines/Navy personnel and civilian workers totaled 12,083 and 1,563, respectively. Cancers among Camp Pendleton Marines/Navy personnel and civilian workers totaled 12,144 and 1,416, respectively. Compared with Camp Pendleton, Camp Lejeune Marines/Navy personnel had aHRs  ≥ 1.20 with CIRs  ≤ 3 for all myeloid cancers (HR = 1.24; 95% CI: 1.03, 1.49), acute myeloid leukemia (HR = 1.38; 95% CI: 1.03, 1.85), myelodysplastic and myeloproliferative syndromes (HR = 1.68; 95% CI: 1.07, 2.62), polycythemia vera (HR = 1.41; 95% CI: 0.94, 2.11), and cancers of the esophagus (HR = 1.27; 95% CI: 1.03, 1.56), larynx (HR = 1.21; 95% CI: 0.98, 1.50), soft tissue (HR = 1.21; 95% CI: 0.92, 1.59), and thyroid (HR = 1.22; 95% CI: 1.03, 1.45). Lymphoma subtypes mantle cell and marginal zone B-cell and lung cancer subtypes adenocarcinoma and non-small cell lung cancer also had aHRs  ≥ 1.20 with CIRs  ≤ 3. Compared with Camp Pendleton, Camp Lejeune civilian workers had aHRs  ≥ 1.20 with CIRs  ≤ 3 for all myeloid cancers (HR = 1.40; 95% CI: 0.83, 2.36), squamous cell lung cancer (HR = 1.63; 95% CI: 1.10, 2.41), and female breast (HR = 1.21; 95% CI: 0.97, 1.52) and ductal cancer (HR = 1.32; 95% CI: 1.02, 1.71). CONCLUSION: Increased risks of several cancers were observed among Marines/Navy personnel and civilian workers exposed to contaminated drinking water at Camp Lejeune compared with Camp Pendleton. https://doi.org/10.1289/EHP14966.

BACKGROUND: Drinking water at U.S. Marine Corps Base (MCB) Camp Lejeune, North Carolina was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. METHODS: A cohort mortality study was conducted of Marines/Navy personnel who, between 1975 and 1985, began service and were stationed at Camp Lejeune (N = 159,128) or MCB Camp Pendleton, California (N = 168,406), and civilian workers employed at Camp Lejeune (N = 7,332) or Camp Pendleton (N = 6,677) between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Mortality follow-up was between 1979 and 2018. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing mortality rates between Camp Lejeune and Camp Pendleton cohorts. The ratio of upper and lower 95% confidence interval (CI) limits, or CIR, was used to evaluate the precision of aHRs. The study focused on underlying causes of death with aHRs ≥ 1.20 and CIRs ≤ 3. RESULTS: Deaths among Camp Lejeune and Camp Pendleton Marines/Navy personnel totaled 19,250 and 21,134, respectively. Deaths among Camp Lejeune and Camp Pendleton civilian workers totaled 3,055 and 3,280, respectively. Compared to Camp Pendleton Marines/Navy personnel, Camp Lejeune had aHRs ≥ 1.20 with CIRs ≤ 3 for cancers of the kidney (aHR = 1.21, 95% CI: 0.95, 1.54), esophagus (aHR = 1.24, 95% CI: 1.00, 1.54) and female breast (aHR = 1.20, 95% CI: 0.73, 1.98). Causes of death with aHRs ≥ 1.20 and CIR > 3, included Parkinson disease, myelodysplastic syndrome and cancers of the testes, cervix and ovary. Compared to Camp Pendleton civilian workers, Camp Lejeune had aHRs ≥ 1.20 with CIRs ≤ 3 for chronic kidney disease (aHR = 1.88, 95% CI: 1.13, 3.11) and Parkinson disease (aHR = 1.21, 95% CI: 0.72, 2.04). Female breast cancer had an aHR of 1.19 (95% CI: 0.76, 1.88), and aHRs ≥ 1.20 with CIRs > 3 were observed for kidney and pharyngeal cancers, melanoma, Hodgkin lymphoma, and chronic myeloid leukemia. Quantitative bias analyses indicated that confounding due to smoking and alcohol consumption would not appreciably impact the findings. CONCLUSION: Marines/Navy personnel and civilian workers likely exposed to contaminated drinking water at Camp Lejeune had increased hazard ratios for several causes of death compared to Camp Pendleton.

OBJECTIVE: To report multiple cause of death (MCOD) occurrence among patients in the United States with amyotrophic lateral sclerosis (ALS). METHODS: Using death certificate data for all ALS deaths from 50 U.S. states and the District of Columbia, 2011-2014, we tabulated MCOD, used association rules mining (ARM) to determine if MCOD occurred together, and calculated standardized mortality odds ratios (SMOR) for select causes, comparing ALS with other U.S. decedents. RESULTS: Among 24,328 death certificates, there were 25,704 MCOD, excluding ALS. ALS was listed as the sole cause of death in n = 11,263 (46%). The most frequent causes of death co-occurring with ALS were respiratory failure (n = 6503; 25.3%), cardiovascular disease (n = 6077; 12.6%), pneumonia (n = 1345; 5.2%), and pneumonitis (n = 856; 3.3%). The SMORs among ALS decedents compared with non-ALS decedents for falls and accidents were 3.4 (95% CI 2.6, 4.3) and 3.0 (95% CI 2.2, 4.2), respectively. From ARM analysis, falls and accidents were both associated with injuries. The most common causes identified were weakly to very strongly associated with being an ALS decedent compared with other U.S. deaths, with SMOR point estimates ranging from 1.3 to 51.1. INTERPRETATION: This study provides information about the natural history of ALS. With knowledge that some causes of death may be preventable, healthcare providers may be able to optimize patient care and possibly postpone mortality and reduce morbidity. Moreover, this study located gaps in data; medical certifiers completing death certificates for ALS decedents should ensure all MCOD data are recorded.

CONTEXT: Lead exposure can harm nearly every organ in the human body. Millions of US children are exposed to lead hazards. Identifying lead-exposed children using blood lead testing is essential for connecting them to appropriate follow-up services. However, blood lead testing is not consistently conducted for at-risk children. Thus, determining which policies help improve blood lead testing rates is essential. OBJECTIVE: This analysis provides critical evidence to better understand which state-level policies are more effective at increasing childhood blood lead testing rates. These include metrics, incentives, other managed care organization guidance, provider guidelines, mandatory reporting of results to state health departments, data sharing between Medicaid and other state agencies, and proof of testing for school enrollment. DESIGN: This analysis included 33 states with complete data on the number of children tested for blood lead in 2017-2018 as reported to the Centers for Disease Control and Prevention. Linear regression modeling was conducted to examine associations between testing rates and the aforementioned policies. Fully adjusted models included percentages of the population living in pre-1980 housing, younger than 6 years with Medicaid coverage, and foreign-born. RESULTS: Strongest unadjusted and adjusted regression coefficients were observed for requiring proof of testing for school enrollment (β = .12, P = .03) and metrics (β = .06, P = .01), respectively. CONCLUSION: Policies associated with higher childhood blood lead testing rates can be used by policy makers; local, state, and federal public health agencies; professional organizations; nonprofit organizations; and others to inform development and implementation of additional policies to increase childhood blood lead testing.

BACKGROUND: Solvents contaminated drinking water supplies at Marine Corps Base Camp Lejeune during 1950s-1985. METHODS: We conducted a case-control study among Marines to evaluate associations between residential exposure to contaminated drinking water at Camp Lejeune and male breast cancer risk. The study included 71 male breast cancer cases and 373 controls identified from the Department of Veteran's Affairs (VA) cancer registry whose military personnel records were available. Controls were selected from cancers not known to be associated with solvent exposure and included 270 skin cancers, 71 mesotheliomas, and 32 bone cancers. Base assignment and risk factor information came from military personnel and VA records. Groundwater contaminant fate/transport and distribution system models provided monthly estimated residential contaminant levels. We conducted exact logistic regression using the 50(th) percentile level among exposed controls to create low and high exposure categories. We calculated 95 % confidence intervals (CIs) to indicate precision of effect estimates. Exploratory analyses used proportional hazards methods to evaluate associations between exposures and age at diagnosis. RESULTS: After adjusting for age at diagnosis, race, and service in Vietnam, the odds ratio (OR) for ever stationed at Camp Lejeune was 1.14 (95 % CI: 0.65, 1.97). Adjusted ORs for high residential cumulative exposures to tetrachloroethylene (PCE), t-1,2 dichloroethylene (DCE), and vinyl chloride were 1.20 [95 % CI: 0.16-5.89], 1.50 [95 % CI: 0.30-6.11], 1.19 [95 % CI: 0.16-5.89], respectively, with a monotonic exposure response relationship for PCE only. However these results were based on two or three cases in the high cumulative exposure categories. Ever stationed at Camp Lejeune and high cumulative exposures to trichloroethylene (TCE), PCE, DCE and vinyl chloride were associated with earlier age at onset for male breast cancer; hazard ratios ranged from 1.4-2.7 with wide confidence intervals for cumulative exposure variables. CONCLUSION: Findings suggested possible associations between male breast cancer and being stationed at Camp Lejeune and cumulative exposure to PCE, DCE, and vinyl chloride. TCE, PCE, DCE and vinyl chloride cumulative exposures showed possible associations with earlier age at onset of male breast cancer. However, this study was limited by small numbers of cases in high exposure categories.

BACKGROUND: Births during 1968-1985 at Camp Lejeune were exposed to drinking water contaminated with trichloroethylene (TCE), tetrachloroethylene (PCE), and benzene. METHODS: We conducted a cross-sectional study to evaluate associations between residential prenatal exposure to contaminated drinking water at Camp Lejeune during 1968-1985 and preterm birth, small for gestational age (SGA), term low birth weight (TLBW), and mean birth weight (MBW) deficit. Birth certificates identified mothers residing at Camp Lejeune at delivery. We analyzed exposure data for the entire pregnancy and individual trimesters. For each period examined, births were categorized as unexposed if mothers did not reside at Camp Lejeune or if their residence on base received uncontaminated drinking water. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels at residences. For PCE and TCE, the exposed group was divided into four levels: < median value, ≥ median value, ≥75th percentile, and ≥90th percentile. For benzene, the exposed group was categorized as <1 part per billion (ppb) versus ≥1 ppb because of sparse data. Magnitude of effect estimates and exposure response relationships were used to assess associations. Confidence intervals (CIs) indicated precision of estimates. RESULTS: For the highest TCE exposure category during the entire pregnancy, odds ratios (ORs) were 1.5 (95% CI: 1.2, 1.9) and 1.3 (95% CI: 0.8, 2.2) for SGA and TLBW, respectively, and reduced MBW beta = -78.3 g (95% CI: -115.0, -41.7). The OR =1.3 (95% CI: 1.0, 1.6) for preterm birth and the highest PCE exposure category during the entire pregnancy. Monotonic exposure-response relationships were observed for benzene exposure during the entire pregnancy and TLBW (highest category OR =1.5, 85% CI: 0.9, 2.3). Although a monotonic association between benzene and adjusted MBW difference was also observed (highest category beta = -36.2 g, 95% CI: -72.3, -0.1), the association disappeared when TCE was also added to the model. We found no evidence suggesting any other associations between outcomes and exposures. CONCLUSION: Findings suggested associations between in utero exposures to TCE and SGA, TLBW and reduced MBW; benzene and TLBW; and PCE and preterm birth.

BACKGROUND: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. METHODS: We conducted a retrospective cohort mortality study of 4,647 civilian, full-time workers employed at Camp Lejeune during 1973-1985 and potentially exposed to contaminated drinking water. We selected a comparison cohort of 4,690 Camp Pendleton workers employed during 1973-1985 and unexposed to contaminated drinking water. Mortality follow-up period was 1979-2008. Cause-specific standardized mortality ratios utilized U.S. age-, sex-, race-, and calendar period-specific mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune and Camp Pendleton workers and assess the effects of estimated cumulative contaminant exposures within the Camp Lejeune cohort. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels in drinking water serving workplaces at Camp Lejeune. The confidence interval (CI) indicated precision of effect estimates. RESULTS: Compared to Camp Pendleton, Camp Lejeune workers had mortality hazard ratios (HRs) >1.50 for kidney cancer (HR = 1.92, 95% CI: 0.58, 6.34), leukemias (HR = 1.59, 95% CI: 0.66, 3.84), multiple myeloma (HR = 1.84, 95% CI: 0.45, 7.58), rectal cancer (HR = 1.65, 95% CI: 0.36, 7.44), oral cavity cancers (HR = 1.93, 95% CI: 0.34, 10.81), and Parkinson's disease (HR = 3.13, 95% CI: 0.76, 12.81). Within the Camp Lejeune cohort, monotonic exposure-response relationships were observed for leukemia and vinyl chloride and PCE, with mortality HRs at the high exposure category of 1.72 (95% CI: 0.33, 8.83) and 1.82 (95% CI: 0.36, 9.32), respectively. Cumulative exposures were above the median for most deaths from cancers of the kidney, esophagus, rectum, prostate, and Parkinson's disease, but small numbers precluded evaluation of exposure-response relationships. CONCLUSION: The study found elevated HRs in the Camp Lejeune cohort for several causes of death including cancers of the kidney, rectum, oral cavity, leukemias, multiple myeloma, and Parkinson's disease. Only 14% of the Camp Lejeune cohort died by end of follow-up, producing small numbers of cause-specific deaths and wide CIs. Additional follow-up would be necessary to comprehensively assess drinking water exposure effects at the base.

BACKGROUND: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. METHODS: We conducted a retrospective cohort mortality study of Marine and Naval personnel who began service during 1975-1985 and were stationed at Camp Lejeune or Camp Pendleton, California during this period. Camp Pendleton's drinking water was uncontaminated. Mortality follow-up was 1979-2008. Standardized Mortality Ratios were calculated using U.S. mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune (N = 154,932) and Camp Pendleton (N = 154,969) cohorts and assess effects of cumulative exposures to contaminants within the Camp Lejeune cohort. Models estimated monthly contaminant levels at residences. Confidence intervals (CIs) indicated precision of effect estimates. RESULTS: There were 8,964 and 9,365 deaths respectively, in the Camp Lejeune and Camp Pendleton cohorts. Compared to Camp Pendleton, Camp Lejeune had elevated mortality hazard ratios (HRs) for all cancers (HR = 1.10, 95% CI: 1.00, 1.20), kidney cancer (HR = 1.35, 95% CI: 0.84, 2.16), liver cancer (HR = 1.42, 95% CI: 0.92, 2.20), esophageal cancer (HR = 1.43 95% CI: 0.85, 2.38), cervical cancer (HR = 1.33, 95% CI: 0.24, 7.32), Hodgkin lymphoma (HR = 1.47, 95% CI: 0.71, 3.06), and multiple myeloma (HR = 1.68, 95% CI: 0.76, 3.72). Within the Camp Lejeune cohort, monotonic categorical cumulative exposure trends were observed for kidney cancer and total contaminants (HR, high cumulative exposure = 1.54, 95% CI: 0.63, 3.75; log10 beta = 0.06, 95% CI: -0.05, 0.17), Hodgkin lymphoma and trichloroethylene (HR, high cumulative exposure = 1.97, 95% CI: 0.55, 7.03; beta = 0.00005, 95% CI: -0.00003, 0.00013) and benzene (HR, high cumulative exposure = 1.94, 95% CI: 0.54, 6.95; beta = 0.00203, 95% CI: -0.00339, 0.00745). Amyotrophic Lateral Sclerosis (ALS) had HR = 2.21 (95% CI: 0.71, 6.86) at high cumulative vinyl chloride exposure but a non-monotonic exposure-response relationship (beta = 0.0011, 95% CI: 0.0002, 0.0020). CONCLUSION: The study found elevated HRs at Camp Lejeune for several causes of death including cancers of the kidney, liver, esophagus, cervix, multiple myeloma, Hodgkin lymphoma and ALS. CIs were wide for most HRs. Because <6% of the cohort had died, long-term follow-up would be necessary to comprehensively assess effects of drinking water exposures at the base.

BACKGROUND: Drinking water supplies at Marine Corps Base Camp Lejeune were contaminated with trichloroethylene, tetrachloroethylene, benzene, vinyl chloride and trans-1,2-dichloroethylene during 1968 through 1985. METHODS: We conducted a case control study to determine if children born during 1968-1985 to mothers with residential exposure to contaminated drinking water at Camp Lejeune during pregnancy were more likely to have childhood hematopoietic cancers, neural tube defects (NTDs), or oral clefts. For cancers, exposures during the first year of life were also evaluated. Cases and controls were identified through a survey of parents residing on base during pregnancy and confirmed by medical records. Controls were randomly sampled from surveyed participants who had a live birth without a major birth defect or childhood cancer. Groundwater contaminant fate and transport and distribution system models provided estimates of monthly levels of drinking water contaminants at mothers' residences. Magnitude of odds ratios (ORs) was used to assess associations. Confidence intervals (CIs) were used to indicate precision of ORs. We evaluated parental characteristics and pregnancy history to assess potential confounding. RESULTS: Confounding was negligible so unadjusted results were presented. For NTDs and average 1st trimester exposures, ORs for any benzene exposure and for trichloroethylene above 5 parts per billion were 4.1 (95% CI: 1.4-12.0) and 2.4 (95% CI: 0.6-9.6), respectively. For trichloroethylene, a monotonic exposure response relationship was observed. For childhood cancers and average 1st trimester exposures, ORs for any tetrachloroethylene exposure and any vinyl chloride exposure were 1.6 (95% CI: 0.5-4.8), and 1.6 (95% CI: 0.5-4.7), respectively. The study found no evidence suggesting any other associations between outcomes and exposures. CONCLUSION: Although CIs were wide, ORs suggested associations between drinking water contaminants and NTDs. ORs suggested weaker associations with childhood hematopoietic cancers.

This report augments guidelines published in 1990 for investigating clusters of health events (CDC. Guidelines for investigating clusters of health events. MMWR 1990;39[No. RR-11]). The 1990 Guidelines considered any noninfectious disease cluster, injuries, birth defects, and previously unrecognized syndromes or illnesses. These new guidelines focus on cancer clusters. State and local health departments can use these guidelines to develop a systematic approach to responding to community concerns regarding cancer clusters. The guidelines are intended to apply to situations in which a health department responds to an inquiry about a suspected cancer cluster in a residential or community setting only. Occupational or medical treatment-related clusters are not included in this report. Since 1990, many improvements have occurred in data resources, investigative techniques, and analytic/statistical methods, and much has been learned from both large- and small-scale cancer cluster investigations. These improvements and lessons have informed these updated guidelines. These guidelines utilize a four-step approach (initial response, assessment, major feasibility study, and etiologic investigation) as a tool for managing a reported cluster. Even if a cancer cluster is identified, there is no guarantee that a common cause or an environmental contaminant will be implicated. Identification of a common cause or an implicated contaminant might be an expected outcome for the concerned community. Therefore, during all parts of an inquiry, responders should be transparent, communicate clearly, and explain their decisions to the community.

OBJECTIVE: To examine the association between cumulative fiber exposure and health outcomes in workers (n = 336) with Libby amphibole exposure. METHODS: Exposure-response relationships were explored by the use of logistic regression, with cumulative fiber exposure modeled in categories and as a continuous variable. RESULTS: The use of spline functions with lifetime cumulative fiber exposure as a continuous variable showed that the odds of localized pleural thickening were significantly elevated at less than 1 f/cc-y. Odds of parenchymal abnormalities, restrictive spirometry, and chronic bronchitis were also significantly elevated at 108, 166, and 24 f/cc-y, respectively. CONCLUSIONS: The odds of several pulmonary health outcomes are correlated with cumulative exposure to Libby amphibole. That relatively low-lifetime cumulative exposures are associated with localized pleural thickening has implications for the non-cancer-risk assessment for Libby amphibole.

In a recent article, TP Clement (2010, hereafter referred to as TPC) discusses the complexities and limitations of "hindcasting" models and criticizes the use of complex models when undertaking investigations of subsurface reactive transport processes. TPC implies that complex numerical models that stimulate reactive transport processes in groundwater are likely if not always an inappropriate tool to apply to "hindcasting" investiagtions and that scientists and engineers who implement these investiagtions using such models are somehow not aware of teh technical and scientific complexities and limitations of such methods and approaches. To illustrate his point of view, TPC uses a case study of an ongoing health study of exposure to volatile organic compounds (VOCs) in drinking water at US Marine Corps Base Camp Lejeune, North Carolina (hereafter referred to as the case-control health study at Camp Lejeune). The article presents some thought-provoking points-of-view. However, we believe there is a lack of detail on several key issues that require specificity and clarification, particularly with respect to modleing approaches and methods, the physics of containment occurrence and reactive transport in teh subsurface, and agency policies for the review and dissemination of data and reports.

OBJECTIVE: To examine the relationship between cumulative fiber exposure (CFE) and mortality in a retrospective cohort study of vermiculite workers exposed to Libby amphibole (n = 1862). METHODS: Extended Cox regression was used to estimate the hazards associated with CFE as a time-dependent covariate of multiple-cause mortality. RESULTS: The Cox models for mesothelioma, asbestosis, lung cancer, and non-malignant respiratory disease were significant with rate ratios that increased monotonically with CFE. The model for deaths due to cardiovascular disease was also significant (rate ratio for CFE ≥44.0 f/cc-y vs <1.4 f/cc-y was 1.5; 95% confidence interval = 1.1 to 2.0). CONCLUSIONS: By using a within-cohort comparison, the results demonstrate a clear exposure-response relationship between CFE and mortality from asbestos-related causes. The finding of an association between CFE and cardiovascular mortality suggests persons exposed to Libby amphibole should be monitored for this outcome.

Two of three water-distribution systems that have historically supplied drinking water to family housing at U.S. Marine Corps Base Camp Lejeune, North Carolina, were contaminated with volatile organic compounds (VOCs). Scientific data relating to the harmful effects of VOCs on a child or fetus are limited. Therefore, the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) is conducting an epidemiological study to evaluate potential associations between in utero and infant (up to 1 year of age) exposures to VOCs in contaminated drinking water at Camp Lejeune and specific birth defects and childhood cancers. The study includes births that occurred during the period 1968-1985 to women who were pregnant while they resided in family housing at Camp Lejeune. To support the epidemiological study, water-modeling techniques are being used to reconstruct historical conditions of groundwater flow, contaminant fate and transport, and the distribution of drinking water contaminated with VOCs. Results for this phase of the study indicate that PCE concentrations in drinking water, delivered to the Tarawa Terrace housing area, exceeded the current maximum contaminant level for PCE of 5 micrograms per liter (µg/L) for 346 months-November 1957-February 1987; the maximum simulated PCE concentration in Tarawa Terrace drinking water was 183 µg/L during March 1984 compared to a measured concentration of 215 µg/L during February 1985.