Long-Term Exposure to Arsenic in Community Water Supplies and Risk of Cardiovascular Disease among Women in the California Teachers Study.

BACKGROUND: Inorganic arsenic in drinking water (wAs) is linked to atherosclerosis and cardiovascular disease. However, risk is uncertain at lower levels present in US community water supplies (CWS), currently regulated at the federal maximum contaminant level of 10µg/L. OBJECTIVES: We evaluated the relationship between long-term wAs exposure from CWS and cardiovascular disease in the California Teachers Study cohort. METHODS: Using statewide health care administrative records from enrollment through follow-up (1995-2018), we identified fatal and nonfatal cases of ischemic heart disease (IHD) and cardiovascular disease (CVD). Participants' residential addresses were linked to a network of CWS boundaries and annual wAs concentrations (1990-2020). Most participants resided in areas served by a CWS (92%). Exposure was calculated as a time-varying, 10-year moving average up to a participant's event, death, or end of follow-up. Using Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of IHD or CVD. We evaluated wAs exposure categorized by concentration thresholds relevant to regulation standards (<1.00, 1.00-2.99, 3.00-4.99, 5.00-9.99, ≥10µg/L) and continuously using a log2-transformation (i.e., per doubling). Models were adjusted for baseline age, neighborhood socioeconomic status, race/ethnicity, body mass index (BMI), and smoking status. We also stratified analyses by age, BMI, and smoking status. RESULTS: Our analysis included 98,250 participants, 6,119 IHD cases, and 9,936 CVD cases. The HRs for IHD at concentration thresholds (reference, <1µg/L) were 1.06 (95% CI: 1.00, 1.12), 1.05 (95% CI: 0.94, 1.17), 1.20 (95% CI: 1.02, 1.41), and 1.42 (95% CI: 1.10, 1.84) for 1.00-2.99µg/L, 3.00-4.99µg/L, 5.00-9.99µg/L, and ≥10µg/L, respectively. HRs for every doubling of wAs exposure were 1.04 (95% CI: 1.02, 1.06) for IHD and 1.02 (95% CI: 1.01, 1.04) for CVD. We observed statistically stronger risk among those ≤55 vs. >55 years of age at enrollment (pinteraction=0.006 and 0.012 for IHD and CVD, respectively). DISCUSSION: Long-term wAs exposure from CWS, at and below the regulatory limit, may increase cardiovascular disease risk, particularly IHD. https://doi.org/10.1289/EHP14410.

Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that have been linked to a number of health outcomes, including those related to immune dysfunction. However, there are limited numbers of epidemiological-based studies that directly examine the association between PFAS exposure and immune responses. METHODS: In this cross-sectional study nested in the California Teachers Study cohort, we measured nine PFAS analytes in serum. Of the 9 analytes, we further evaluated four (PFHxS [perfluorohexane sulfonate], PFNA [perfluorononanoic acid], PFOA [perfluorooctanoic acid], PFOS [perfluorooctanesulfonic acid]) that had detection levels of > 80 %, in relation to 16 systemic inflammatory/immune markers and corresponding immune pathways (Th1 [pro-inflammatory/macrophage activation], B-cell activation, and T-cell activation). Study participants (n = 722) were female, completed a questionnaire regarding various health measures and behaviors, and donated a blood sample between 2013-2016. The association between PFAS analytes and individual immune markers and pathways were evaluated by calculating odds ratios (OR) and 95 % confidence intervals (CI) in a logistic regression model. PFAS analytes were evaluated both as a dichotomous exposure (above or below the respective median) and as a continuous variable (per 1 unit increase [ng/mL]). RESULTS: The prevalence of detecting any PFAS analyte rose with increasing age, with the highest PFAS prevalence observed among those aged 75 + years and the lowest PFAS prevalence observed among those aged 40-49 years (study participant age range: 40-95 years). Significant associations with BAFF (B-cell activating factor) levels above the median were observed among participants with elevated (defined as above the median) levels of PFHxS (OR=1.53), PFOA (OR=1.43), and PFOS (OR=1.40). Similarly, there were statistically significant associations between elevated levels of PFHxS and TNFRII (tumor necrosis factor receptor 2) levels (OR=1.78) and IL2Rα (interleukin 2 receptor subunit alpha) levels (OR=1.48). We also observed significant inverse associations between elevated PFNA and sCD14 (soluble cluster of differentiation 14) (OR=0.73). No significant associations were observed between elevated PFNA and any immune marker. Evaluation of PFAS exposures as continuous exposures in association with dichotomized cytokines were generally consistent with the dichotomized associations. CONCLUSIONS: PFAS exposure was associated with altered levels of circulating inflammatory/immune markers; the associations were specific to PFAS analyte and immune marker. If validated, our results may suggest potential immune mechanisms underlying associations between the different PFAS analytes and adverse health outcomes.

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.

Association between pre-diagnosis recreational physical activity and risk of breast cancer recurrence: the California Teachers Study.

PURPOSE: Studies have reported inverse associations of pre-diagnosis recreational physical activity (RPA) level with all-cause and breast cancer (BCa)-specific mortality among BCa patients. However, the association between pre-diagnosis RPA level and BCa recurrence is unclear. We investigated the association between pre-diagnosis RPA level and risk of BCa recurrence in the California Teachers Study (CTS). METHODS: Stage I-IIIb BCa survivors (n = 6,479) were followed with median of 7.4 years, and 474 BCa recurrence cases were identified. Long-term (from high school to age at baseline questionnaire, or, age 55 years, whichever was younger) and baseline (past 3 years reported at baseline questionnaire) pre-diagnosis RPA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of BCa recurrence overall and by estrogen receptor (ER)/progesterone receptor (PR) status. RESULTS: Long-term RPA was not associated with BCa recurrence risk (ptrend = 0.99). The inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was marginally significant (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.79, 95% CI = 0.60-1.03; ptrend = 0.07). However, the association became non-significant after adjusting for post-diagnosis RPA (ptrend = 0.65). An inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was observed in ER-PR- cases (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.31, 95% CI = 0.13-0.72; ptrend = 0.04), but not in ER+ or PR+ cases (ptrend = 0.97). CONCLUSIONS: Our data indicates that the benefit of baseline RPA on BCa recurrence may differ by tumor characteristics. This information may be particularly important for populations at higher risk of ER-PR- BCa.

Construction of residential histories to estimate long-term environmental exposures in the California Teachers Study cohort.

Environmental epidemiologic studies using geospatial data often estimate exposure at a participant's residence upon enrollment, but mobility during the exposure period can lead to misclassification. We aimed to mitigate this issue by constructing residential histories for participants in the California Teachers Study through follow-up (1995-2018). Address records have been collected from the US Postal Service, LexisNexis, Experian, and California Cancer Registry. We identified records of the same address based on geo-coordinate distance (≤250 m) and street name similarity. We consolidated addresses, prioritizing those confirmed by participants during follow-up questionnaires, and estimating the duration lived at each address using dates associated with records (e.g., date-first-seen). During 23 years of follow-up, about half of participants moved (48%, including 14% out-of-state). We observed greater mobility among younger women, Hispanic/Latino women, and those in metropolitan and lower socioeconomic status areas. The cumulative proportion of in-state movers remaining eligible for analysis was 21%, 32%, and 41% at 5, 10, and 20 years post enrollment, respectively. Using self-reported information collected 10 years after enrollment, we correctly identified 94% of movers and 95% of non-movers as having moved or not moved from their enrollment address. This dataset provides a foundation for estimating long-term environmental exposures in diverse epidemiologic studies in this cohort. IMPACT: Our efforts in constructing residential histories for California Teachers Study participants through follow-up (1995-2018) benefit future environmental epidemiologic studies. Address availability during the exposure period can mitigate misclassification due to residential changes, especially when evaluating long-term exposures and chronic health outcomes. This can reduce differential misclassification among more mobile subgroups, including younger women and those from lower socioeconomic and urban areas. Our approach to consolidating addresses from multiple sources showed high accuracy in comparison to self-reported residential information. The residential dataset produced from this analysis provides a valuable tool for future studies, ultimately enhancing our understanding of environmental health impacts.

Mental health and social connection among older lesbian and bisexual women.

OBJECTIVE: To assess differences in psychosocial and mental health outcomes between older lesbian and bisexual women compared to heterosexual women. DESIGN: Cross sectional study. SETTING: The study was carried out in the California Teachers Study, a prospective cohort study. PARTICIPANTS: Self-identified heterosexual (n = 35,846), lesbian (n = 710), and bisexual (n = 253) women 50 years of age and older were enrolled. MEASUREMENTS: Validated questionnaires were used to measure social connection, overall happiness, and depression. Logistic regression modeling was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing lesbian and bisexual women separately to heterosexual women in relation to psychosocial and mental health outcomes. RESULTS: After controlling for age and marital status, older bisexual women were significantly more likely to report lack of companionship (OR = 2.00; 95% CI, 1.30-3.12) and feeling left out (OR = 2.33; 95% CI, 1.36-3.97) compared to older heterosexual women. The odds of reporting feeling isolated from others was significantly higher in lesbian (OR = 1.56; 95% CI, 1.06-2.30) and bisexual women (OR = 2.30; 95% CI, 1.37-3.87) than in heterosexual women. The OR (95% CI) for reporting not being very happy overall was 1.96 (CI, 1.09-3.52) in bisexual women and 1.40 (0.92-2.14) in lesbian women compared to heterosexual women. The likelihood of reporting diagnosed depression was significantly higher in lesbian women (OR = 1.65; 95% CI, 1.38-1.97) and bisexual women (OR = 2.21; 95% CI, 1.67-2.93) compared to heterosexual women. CONCLUSION: Inclusion of lesbian and bisexual women in aging research is essential to understand their unique mental and other health needs, including those specific to bisexual women.

Insights from Adopting a Data Commons Approach for Large-scale Observational Cohort Studies: The California Teachers Study.

BACKGROUND: Large-scale cancer epidemiology cohorts (CEC) have successfully collected, analyzed, and shared patient-reported data for years. CECs increasingly need to make their data more findable, accessible, interoperable, and reusable, or FAIR. How CECs should approach this transformation is unclear. METHODS: The California Teachers Study (CTS) is an observational CEC of 133,477 participants followed since 1995-1996. In 2014, we began updating our data storage, management, analysis, and sharing strategy. With the San Diego Supercomputer Center, we deployed a new infrastructure based on a data warehouse to integrate and manage data and a secure and shared workspace with documentation, software, and analytic tools that facilitate collaboration and accelerate analyses. RESULTS: Our new CTS infrastructure includes a data warehouse and data marts, which are focused subsets from the data warehouse designed for efficiency. The secure CTS workspace utilizes a remote desktop service that operates within a Health Insurance Portability and Accountability Act (HIPAA)- and Federal Information Security Management Act (FISMA)-compliant platform. Our infrastructure offers broad access to CTS data, includes statistical analysis and data visualization software and tools, flexibly manages other key data activities (e.g., cleaning, updates, and data sharing), and will continue to evolve to advance FAIR principles. CONCLUSIONS: Our scalable infrastructure provides the security, authorization, data model, metadata, and analytic tools needed to manage, share, and analyze CTS data in ways that are consistent with the NCI's Cancer Research Data Commons Framework. IMPACT: The CTS's implementation of new infrastructure in an ongoing CEC demonstrates how population sciences can explore and embrace new cloud-based and analytics infrastructure to accelerate cancer research and translation.See all articles in this CEBP Focus section, "Modernizing Population Science."

Using Marketing Automation to Modernize Data Collection in the California Teachers Study Cohort.

BACKGROUND: Like other cancer epidemiologic cohorts, the California Teachers Study (CTS) has experienced declining participation to follow-up questionnaires; neither the reasons for these declines nor the steps that could be taken to mitigate these trends are fully understood. METHODS: The CTS offered their 6th study questionnaire (Q6) in the fall of 2017 using an integrated, online system. The team delivered a Web and mobile-adaptive questionnaire to 45,239 participants via e-mail using marketing automation technology. The study's integrated platform captured data on recruitment activities that may influence overall response, including the date and time invitations and reminders were e-mailed and the date and time questionnaires were started and submitted. RESULTS: The overall response rate was 43%. Participants ages 65 to 69 were 25% more likely to participate than their younger counterparts (OR = 1.25; 95% CI, 1.18-1.32) and nonwhite participants were 28% less likely to participate than non-Hispanic white cohort members (OR = 0.72; 95% CI, 0.68-0.76). Previous questionnaire participation was strongly associated with response (OR = 6.07; 95% CI, 5.50-6.70). Invitations sent after 2 pm had the highest response (OR = 1.75; 95% CI, 1.65-1.84), as did invitations sent on Saturdays (OR = 1.48; 95% CI, 1.36-1.60). CONCLUSIONS: An integrated system that captures paradata about questionnaire recruitment and response can enable studies to quantify the engagement patterns and communication desires of cohort members. IMPACT: As cohorts continue to collect scientific data, it is imperative to collect and analyze information on how participants engage with the study.See all articles in this CEBP Focus section, "Modernizing Population Science."