Urinary biomonitoring of glyphosate exposure among male farmers and nonfarmers in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study.

Glyphosate is the most widely applied herbicide worldwide. Glyphosate biomonitoring data are limited for agricultural settings. We measured urinary glyphosate concentrations and assessed exposure determinants in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study. We selected four groups of BEEA participants based on self-reported pesticide exposure: recently exposed farmers with occupational glyphosate use in the last 7 days (n = 98), farmers with high lifetime glyphosate use (>80th percentile) but no use in the last 7 days (n = 70), farming controls with minimal lifetime use (n = 100), and nonfarming controls with no occupational pesticide exposures and no recent home/garden glyphosate use (n = 100). Glyphosate was quantified in first morning void urine using ion chromatography isotope-dilution tandem mass spectrometry. We estimated associations between urinary glyphosate concentrations and potential determinants using multivariable linear regression. Glyphosate was detected (≥0.2 µg/L) in urine of most farmers with recent (91 %) and high lifetime (93 %) use, as well as farming (88 %) and nonfarming (81 %) controls; geometric mean concentrations were 0.89, 0.59, 0.46, and 0.39 µg/L (0.79, 0.51, 0.42, and 0.37 µg/g creatinine), respectively. Compared with both control groups, urinary glyphosate concentrations were significantly elevated among recently exposed farmers (P < 0.0001), particularly those who used glyphosate in the previous day [vs. nonfarming controls; geometric mean ratio (GMR) = 5.46; 95 % confidence interval (CI): 3.75, 7.93]. Concentrations among high lifetime exposed farmers were also elevated (P < 0.01 vs. nonfarming controls). Among recently exposed farmers, glyphosate concentrations were higher among those not wearing gloves when applying glyphosate (GMR = 1.91; 95 % CI: 1.17, 3.11), not wearing long-sleeved shirts when mixing/loading glyphosate (GMR = 2.00; 95 % CI: 1.04, 3.86), applying glyphosate exclusively using broadcast/boom sprayers (vs. hand sprayer only; GMR = 1.70; 95 % CI: 1.00, 2.92), and applying glyphosate to crops (vs. non-crop; GMR = 1.72; 95 % CI: 1.04, 2.84). Both farmers and nonfarmers are exposed to glyphosate, with recency of occupational glyphosate use being the strongest determinant of urinary glyphosate concentrations. Continued biomonitoring of glyphosate in various settings is warranted.

Pesticide use and inflammatory bowel disease in licensed pesticide applicators and spouses in the Agricultural Health Study.

BACKGROUND: Pesticide exposure has been linked to some autoimmune diseases and colorectal cancer, possibly via alteration of gut microbiota or other mechanisms. While pesticides have been linked to gut dysbiosis and inflammation in animal models, few epidemiologic studies have examined pesticides in relation to inflammatory bowel disease (IBD). OBJECTIVES: We evaluated use of pesticides and incident IBD in 68,480 eligible pesticide applicators and spouses enrolled in the Agricultural Health Study. METHODS: Self-reported IBD cases were identified from follow-up questionnaires between enrollment (1993-1997) and 2022. We evaluated IBD incidence in relation to self-reported ever use of 50 pesticides among applicators and spouses. We also explored associations with intensity-weighted lifetime days (IWLD) of pesticide use among male applicators. Covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression. RESULTS: We identified 454 IBD cases, including 227 among male applicators. In analyses with applicators and spouses combined, associations were positive (HR > 1.2) for ever vs. never use of five organochlorine insecticides, three organophosphate insecticides, one fungicide, and five herbicides. HRs were highest for dieldrin (HR = 1.59, 95%CI: 1.03, 2.44), toxaphene (HR = 1.61, 95%CI: 1.17, 2.21), parathion (HR = 1.42, 95%CI: 1.03, 1.95), and terbufos (HR = 1.53, 95%CI: 1.19, 1.96). We had limited power in many IWLD of pesticide use analyses and did not find clear evidence of exposure-response trends; however, we observed elevated HRs in all tertiles of IWLD use of terbufos compared to never use (T1 vs. never use HR = 1.52, 95%CI: 1.03, 2.24; T2 vs. never use HR = 1.53, 95%CI: 1.04, 2.26; T3 vs. never use HR = 1.51, 95%CI: 1.03, 2.23). CONCLUSIONS: Exposure to specific pesticides was associated with elevated hazards of IBD. These findings may have public health importance given the widespread use of pesticides and the limited number of known modifiable environmental risk factors for IBD.

An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort.

BACKGROUND: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. OBJECTIVE: We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. METHODS: Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. RESULTS: Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [rate ratios (RR)=1.24; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (RRQ4=1.20; 95% CI: 0.95, 1.52; p-trend=0.19), particularly among those <60 years old (RRQ4=3.04; 95% CI: 1.61, 5.75; p-trend<0.001; p-interaction=0.04). Among applicators <50 years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (RR=2.43; 95% CI: 1.10, 5.38; p-interaction=0.60). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (RRT3: 2.54; 95% CI: 0.97, 6.62; p-trend=0.31). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (RRT3=3.04; 95% CI: 1.45, 6.36; p-trend=0.07) and kidney (RRQ4=1.62; 95% CI: 1.15, 2.29; p-trend<0.005) cancers. DISCUSSION: We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684.

Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study.

BACKGROUND: Nitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD). OBJECTIVES: We investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation. METHODS: We performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993-1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999-2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake. RESULTS: We identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C

Occupational farm work activities influence workers' indoor home microbiome.

BACKGROUND: Farm work entails a heterogeneous mixture of exposures that vary considerably across farms and farmers. Farm work is associated with various health outcomes, both adverse and beneficial. One mechanism by which farming exposures can impact health is through the microbiome, including the indoor home environment microbiome. It is unknown how individual occupational exposures shape the microbial composition in workers' homes. OBJECTIVES: We investigated associations between farm work activities, including specific tasks and pesticide use, and the indoor microbiome in the homes of 468 male farmers. METHODS: Participants were licensed pesticide applicators, mostly farmers, enrolled in the Agricultural Lung Health Study from 2008 to 2011. Vacuumed dust from participants' bedrooms underwent whole-genome shotgun sequencing for indoor microbiome assessment. Using questionnaire data, we evaluated 6 farm work tasks (processing of either hay, silage, animal feed, fertilizer, or soy/grains, and cleaning grain bins) and 19 pesticide ingredients currently used in the past year, plus 7 banned persistent pesticide ingredients ever used. RESULTS: All 6 work tasks were associated with increased microbial diversity levels, with a positive dose-response for the total number of tasks performed (P = 0.001). All tasks were associated with altered microbial compositions (weighted UniFrac P = 0.001) and with higher abundance of specific microbes, including soil-based commensal microbes such as Haloterrigena. Among the 19 pesticides, current use of glyphosate and past use of lindane were associated with increased microbial diversity (P = 0.02-0.04). Ten currently used pesticides and all 7 banned pesticides were associated with altered microbial composition (P = 0.001-0.04). Six pesticides were associated with differential abundance of certain microbes. DISCUSSION: Different farm activities and exposures can uniquely impact the dust microbiome inside homes. Our work suggests that changes to the home microbiome could serve as one pathway for how occupational exposures impact the health of workers and their cohabitating family members, offering possible future intervention targets.

Glyphosate Use and Mosaic Loss of Chromosome Y among Male Farmers in the Agricultural Health Study.

BACKGROUND: Glyphosate is the most commonly used herbicide worldwide and has been implicated in the development of certain hematologic cancers. Although mechanistic studies in human cells and animals support the genotoxic effects of glyphosate, evidence in human populations is scarce. OBJECTIVES: We evaluated the association between lifetime occupational glyphosate use and mosaic loss of chromosome Y (mLOY) as a marker of genotoxicity among male farmers. METHODS: We analyzed blood-derived DNA from 1,606 farmers ≥50 years of age in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. mLOY was detected using genotyping array intensity data in the pseudoautosomal region of the sex chromosomes. Cumulative lifetime glyphosate use was assessed using self-reported pesticide exposure histories. Using multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between glyphosate use and any detectable mLOY (overall mLOY) or mLOY affecting ≥10% of cells (expanded mLOY). RESULTS: Overall, mLOY was detected in 21.4% of farmers, and 9.8% of all farmers had expanded mLOY. Increasing total lifetime days of glyphosate use was associated with expanded mLOY [highest vs. lowest quartile; OR=1.75 (95% CI: 1.00, 3.07), ptrend=0.03] but not with overall mLOY; the associations with expanded mLOY were most apparent among older (≥70 years of age) men [OR=2.30 (95% CI: 1.13, 4.67), ptrend=0.01], never smokers [OR=2.32 (95% CI: 1.04, 5.21), ptrend=0.04], and nonobese men [OR=2.04 (95% CI: 0.99, 4.19), ptrend=0.03]. Similar patterns of associations were observed for intensity-weighted lifetime days of glyphosate use. DISCUSSION: High lifetime glyphosate use could be associated with mLOY affecting a larger fraction of cells, suggesting glyphosate could confer genotoxic or selective effects relevant for clonal expansion. As the first study to investigate this association, our findings contribute novel evidence regarding the carcinogenic potential of glyphosate and require replication in future studies. https://doi.org/10.1289/EHP12834.

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.

Tumor-Associated and Systemic Autoimmunity in Pre-Clinical Breast Cancer among Post-Menopausal Women.

Autoantibodies to tumor-associated antigens (anti-TAA) are potential biomarkers for breast cancer, but their relationship systemic autoimmunity as ascertained though antinuclear antibodies (ANA) is unknown and warrants consideration given the common occurrence of autoimmunity and autoimmune diseases among women. The relationship between anti-TAAs and ANA among women who were later diagnosed with breast cancer and others who remained cancer free in the Women's Health Initiative cohort. The study sample included 145 post-menopausal women with baseline ANA data. A total of 37 ANA-positive women who developed breast cancer (i.e., cases; mean time to diagnosis 6.8 years [SE 3.9]) were matched to a random sample of 36 ANA-negative cases by age and time to diagnosis. An age-matched control sample was selected including 35 ANA-positive and 37 ANA-negative women who did not develop breast cancer (i.e., controls; follow-up time ~13 years [SE 3]). Baseline sera were assessed for Immunoglobulin G (IgG) antibodies, measured by custom microarray for 171 breast and other cancer-associated TAA. We used linear regression to estimate cross-sectional associations of ANA with log-transformed anti-TAA among cases and controls. Most anti-TAA did not vary by ANA status. Two anti-TAA were elevated in ANA-positive compared to ANA-negative cases: anti-PGM3 (p = 0.004) and anti-TTN (p = 0.005, especially in cases up to 7 years before diagnosis, p = 0.002). Anti-TAA antibodies were not generally related to ANA, a common marker of systemic autoimmunity. Associations of ANA with particular antigens inducing autoimmunity prior to breast cancer warrant further investigation.

High pesticide exposures events, pesticide poisoning, and shingles: A medicare-linked study of pesticide applicators in the agricultural health study.

OBJECTIVES: Self-reported shingles was associated with history of high pesticide exposure events (HPEE) in licensed pesticide applicators aged >60 years in the Agricultural Health Study (AHS). In the current study, using AHS-linked Medicare claims data, we examined incident shingles in relation to pesticide-related illness and pesticide poisoning, as well as HPEE. METHODS: We studied 22,753 licensed private pesticide applicators (97% white males, enrolled in the AHS 1993-97), aged ≥66 years with >12 consecutive months of Medicare fee-for-service hospital and outpatient coverage between 1999 and 2016. Incident shingles was identified based on having ≥1 shingles claim(s) after 12 months without claims. At AHS enrollment, participants were asked if they ever sought medical care or were hospitalized for pesticide-related illness, and a supplemental questionnaire (completed by 51%) asked about HPEE and poisoning. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression, adjusted for age, sex, race, state, and education. RESULTS: Over 192,053 person-years (PY), 2396 applicators were diagnosed with shingles (10.5%; age-standardized rate, 13.6 cases per 1,000PY), with higher rates among those reporting hospitalization for pesticide-related illness, pesticide poisoning, and HPEE (23.2, 22.5, and 16.6 per 1,000PY, respectively). In adjusted models, shingles was associated with hospitalization for pesticide-related illness (HR 1.69; 1.18, 2.39), poisoning (1.49; 1.08, 1.46), and HPEE (1.23; 95% CI = 1.03, 1.46), especially HPEE plus medical care/poisoning (1.78; 1.30, 2.43). CONCLUSION: These novel findings suggest that acute, high-level, and clinically impactful pesticide exposures may increase risk of shingles in subsequent years to decades following exposure.

Occupational Farm Work Activities Influence Workers' Indoor Home Microbiome.

Background: Farm work entails a heterogeneous mixture of exposures that vary considerably across farms and farmers. Farm work is associated with various health outcomes, both adverse and beneficial. One mechanism by which farming exposures can impact health is through the microbiome, including the indoor built environment microbiome. It is unknown how individual occupational exposures shape the microbial composition in workers' homes. Objectives: We investigated associations between farm work activities, including specific tasks and pesticide use, and the indoor microbiome in the homes of 468 male farmers. Methods: Participants were licensed pesticide applicators, mostly farmers, enrolled in the Agricultural Lung Health Study from 2008-2011. Vacuumed dust from participants' bedrooms underwent whole-genome shotgun sequencing for indoor microbiome assessment. Using questionnaire data, we evaluated 6 farm work tasks (processing of either hay, silage, animal feed, fertilizer, or soy/grains, and cleaning grain bins) and 19 pesticide ingredients currently used in the past year, plus 7 persistent banned pesticide ingredients ever used. Results: All 6 work tasks were associated with increased within-sample microbial diversity, with a positive dose-response for the sum of tasks (p=0.001). All tasks were associated with altered overall microbial compositions (weighted UniFrac p=0.001) and with higher abundance of specific microbes, including soil-based microbes such as Haloterrigena. Among the 19 pesticides, only current use of glyphosate and past use of lindane were associated with increased within-sample diversity (p=0.02-0.04). Ten currently used pesticides and all 7 banned pesticides were associated with altered microbial composition (p=0.001-0.04). Six pesticides were associated with differential abundance of certain microbes. Discussion: Specific farm activities and exposures can impact the dust microbiome inside homes. Our work suggests that occupational farm exposures could impact the health of workers and their families through modifying the indoor environment, specifically the microbial composition of house dust, offering possible future intervention targets.

Joint associations between established genetic susceptibility loci, pesticide exposures, and risk of prostate cancer.

More than 200 genetic variants have been independently associated with prostate cancer risk. Studies among farmers have also observed increased prostate cancer risk associated with exposure to specific organophosphate (fonofos, terbufos, malathion, dimethoate) and organochlorine (aldrin, chlordane) insecticides. We examined the joint associations between these pesticides, established prostate cancer loci, and prostate cancer risk among 1,162 cases (588 aggressive) and 2,206 frequency-matched controls nested in the Agricultural Health Study cohort. History of lifetime pesticide use was combined with a polygenic risk score (PRS) generated using 256 established prostate cancer risk variants. Logistic regression models estimated the joint associations of the pesticides, the PRS, and the 256 individual genetic variants with risk of total and aggressive prostate cancer. Likelihood ratio tests assessed multiplicative interaction. We observed interaction between ever use of fonofos and the PRS in relation to total and aggressive prostate cancer risk. Compared to the reference group (never use, PRS < median), men with ever use of fonofos and PRS > median had elevated risks of total (OR 1.35 [1.06-1.73], p-interaction = 0.03) and aggressive (OR 1.49 [1.09-2.04], p-interaction = 0.19) prostate cancer. There was also suggestion of interaction between pesticides and individual genetic variants occurring in regions associated with DNA damage response (CDH3, EMSY genes) and with variants related to altered androgen receptor-driven transcriptional programs critical for prostate cancer. Our study provides evidence that men with greater genetic susceptibility to prostate cancer may be at higher risk if they are also exposed to pesticides and suggests potential mechanisms by which pesticides may increase prostate cancer risk.

Anti-dense fine speckled 70 (DFS70) autoantibodies: correlates and increasing prevalence in the United States.

Objective: Recent studies report high-titer anti-dense fine speckled 70 (DFS70) autoantibodies in persons with inflammatory conditions, but the clinical significance remains unclear. Our goals were to estimate anti-DFS70 autoantibody prevalence, identify correlates, and assess time trends. Methods: Serum antinuclear antibodies (ANA) were measured by indirect immunofluorescence assay on HEp-2 cells in 13,519 participants ≥12 years old from three time periods (1988-1991, 1999-2004, 2011-2012) of the National Health and Nutrition Examination Survey. ANA-positive participants with dense fine speckled staining were evaluated for anti-DFS70 antibodies by enzyme-linked immunosorbent assay. We used logistic models adjusted for survey-design variables to estimate period-specific anti-DFS70 antibody prevalence in the US, and we further adjusted for sex, age, and race/ethnicity to identify correlates and assess time trends. Results: Women were more likely than men (odds ratio (OR)=2.97), black persons were less likely than white persons (OR=0.60), and active smokers were less likely than nonsmokers (OR=0.28) to have anti-DFS70 antibodies. The prevalence of anti-DFS70 antibodies increased from 1.6% in 1988-1991 to 2.5% in 1999-2004 to 4.0% in 2011-2012, which corresponds to 3.2 million, 5.8 million, and 10.4 million seropositive individuals, respectively. This increasing time trend in the US population (P<0.0001) was modified in some subgroups and was not explained by concurrent changes in tobacco smoke exposure. Some, but not all, anti-DFS70 antibody correlates and time trends resembled those reported for total ANA. Conclusion: More research is needed to elucidate anti-DFS70 antibody triggers, their pathologic or potentially protective influences on disease, and their possible clinical implications.

Metagenomics reveals novel microbial signatures of farm exposures in house dust.

Indoor home dust microbial communities, important contributors to human health, are shaped by environmental factors, including farm-related exposures. Advanced metagenomic whole genome shotgun sequencing (WGS) improves detection and characterization of microbiota in the indoor built-environment dust microbiome, compared to conventional 16S rRNA amplicon sequencing (16S). We hypothesized that the improved characterization of indoor dust microbial communities by WGS will enhance detection of exposure-outcome associations. The objective of this study was to identify novel associations of environmental exposures with the dust microbiome from the homes of 781 farmers and farm spouses enrolled in the Agricultural Lung Health Study. We examined various farm-related exposures, including living on a farm, crop versus animal production, and type of animal production, as well as non-farm exposures, including home cleanliness and indoor pets. We assessed the association of the exposures on within-sample alpha diversity and between-sample beta diversity, and the differential abundance of specific microbes by exposure. Results were compared to previous findings using 16S. We found most farm exposures were significantly positively associated with both alpha and beta diversity. Many microbes exhibited differential abundance related to farm exposures, mainly in the phyla Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. The identification of novel differential taxa associated with farming at the genera level, including Rhodococcus, Bifidobacterium, Corynebacterium, and Pseudomonas, was a benefit of WGS compared to 16S. Our findings indicate that characterization of dust microbiota, an important component of the indoor environment relevant to human health, is heavily influenced by sequencing techniques. WGS is a powerful tool to survey the microbial community that provides novel insights on the impact of environmental exposures on indoor dust microbiota. These findings can inform the design of future studies in environmental health.

Life Events, Caregiving, and Risk of Autoimmune Rheumatic Diseases in the Women's Health Initiative Observational Study.

OBJECTIVE: Growing evidence suggests psychosocial stressors may increase risk of developing autoimmune disease. We examined stressful life events and caregiving in relation to incident rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in the Women's Health Initiative Observational Study cohort. METHODS: The sample of postmenopausal women included 211 incident RA or SLE cases reported within 3 years after enrollment, confirmed by use of disease-modifying antirheumatic drugs (i.e., probable RA/SLE), and 76,648 noncases. Baseline questionnaires asked about life events in the past year, caregiving, and social support. We used Cox regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs), adjusting for age, race/ethnicity, occupational class, education, pack-years of smoking and BMI. RESULTS: Incident RA/SLE was associated with reporting 3 or more life events (e.g., age-adjusted HR 1.70 [95% CI 1.14, 2.53]; P for trend = 0.0026). Elevated HRs were noted for physical (HR 2.48 [95% CI 1.02, 6.04]) and verbal (HR 1.34 [0.89, 2.02]) abuse (P for trend = 0.0614), 2 or more interpersonal events (HR 1.23 [95% CI 0.87, 1.73]; P for trend = 0.2403), financial stress (HR 1.22 [95% CI 0.90, 1.64]), and caregiving 3 or more days per week (HR 1.25 [95% CI 0.87, 1.81]; P for trend = 0.2571). Results were similar, excluding women with baseline symptoms of depression or moderate-to-severe joint pain in the absence of diagnosed arthritis. CONCLUSION: Our findings support the idea that diverse stressors may increase risk of developing probable RA or SLE in postmenopausal women, supporting the need for further studies in autoimmune rheumatic diseases, including childhood adverse events, life event trajectories, and modifying psychosocial and socioeconomic factors.

Metagenomics reveals novel microbial signatures of farm exposures in house dust.

Indoor home dust microbial communities, important contributors to human health outcomes, are shaped by environmental factors, including farm-related exposures. Detection and characterization of microbiota are influenced by sequencing methodology; however, it is unknown if advanced metagenomic whole genome shotgun sequencing (WGS) can detect novel associations between environmental exposures and the indoor built-environment dust microbiome, compared to conventional 16S rRNA amplicon sequencing (16S). This study aimed to better depict indoor dust microbial communities using WGS to investigate novel associations with environmental risk factors from the homes of 781 farmers and farm spouses enrolled in the Agricultural Lung Health Study. We examined various farm-related exposures, including living on a farm, crop versus animal production, and type of animal production, as well as non-farm exposures, including home cleanliness and indoor pets. We assessed the association of the exposures on within-sample alpha diversity and between-sample beta diversity, and the differential abundance of specific microbes by exposure. Results were compared to previous findings using 16S. We found most farm exposures were significantly positively associated with both alpha and beta diversity. Many microbes exhibited differential abundance related to farm exposures, mainly in the phyla Actinobacteria, Bacteroidetes, Firmicutes , and Proteobacteria . The identification of novel differential taxa associated with farming at the genera level, including Rhodococcus, Bifidobacterium, Corynebacterium , and Pseudomonas , was a benefit of WGS compared to 16S. Our findings indicate that characterization of dust microbiota, an important component of the indoor environment relevant to human health, is heavily influenced by sequencing techniques. WGS is a powerful tool to survey the microbial community that provides novel insights on the impact of environmental exposures on indoor dust microbiota, and should be an important consideration in designing future studies in environmental health.

Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study.

BACKGROUND: Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study. METHODS: This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker. RESULTS: Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use. CONCLUSIONS: Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide.

Racial/Ethnic Differences in Associations Between Traumatic Childhood Experiences and Both Metabolic Syndrome Prevalence and Type 2 Diabetes Risk Among a Cohort of U.S. Women.

OBJECTIVE: Childhood adversity has been associated with metabolic syndrome (MetS) and type 2 diabetes risk in adulthood. However, studies have yet to investigate traumatic childhood experiences (TCEs) beyond abuse and neglect (e.g., natural disaster) while considering potential racial/ethnic differences. RESEARCH DESIGN AND METHODS: To investigate race/ethnicity as a potential modifier of the association between TCEs, MetS, and type 2 diabetes, we used prospectively collected data from 42,173 eligible non-Hispanic White (NHW; 88%), Black/African American (BAA; 7%), and Hispanic/Latina (4%) Sister Study participants (aged 35-74 years) enrolled from 2003 to 2009. A modified Brief Betrayal Trauma Survey captured TCEs. At least three prevalent metabolic abnormalities defined MetS, and self-report of a new diagnosis during the study period defined type 2 diabetes. We used adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes over a mean ± SD follow-up of 11.1 ± 2.7 years, overall and by race/ethnicity. We also tested for modification and mediation by MetS. RESULTS: Incident cases of type 2 diabetes were reported (n = 2,479 among NHW, 461 among BAA, and 281 among Latina participants). Reporting any TCEs (50% among NHW, 53% among BAA, and 51% among Latina participants) was associated with a 13% higher risk of type 2 diabetes (HR 1.13; 95% CI 1.04-1.22). Associations were strongest among Latina participants (HR 1.64 [95% CI 1.21-2.22] vs. 1.09 for BAA and NHW). MetS was not a modifier but mediated (indirect effect, HR 1.01 [95% CI 1.00-1.01]; P = 0.02) the overall association. CONCLUSIONS: TCE and type 2 diabetes associations varied by race/ethnicity and were partially explained by MetS.

Neighborhood disadvantage and immune-related illnesses among residents living in the US Gulf States.

PURPOSE: Neighborhood disadvantage has been associated with increased risk for pneumonia and influenza-associated hospitalizations. Few studies, however, have investigated how neighborhood disadvantage may influence immune-related illnesses. The aim of this study was to examine the association between neighborhooddisadvantage and immune-related illnesses. METHODS: We used data from the Gulf Long-term Follow-up (GuLF) Study (n = 32,608). Our analytic sample included home visit participants (n = 11,193) who had complete information on exposure and covariates (n = 10,543). Neighborhood disadvantage was assessed using the 2013 Area Deprivation Index (ADI), which assigns a ranking of 1 to 100 for lowest to highest disadvantage. We linked ADI to participants' geocoded enrollment addresses at the census block group level. ADI was categorized into quartiles based on the national distribution with the first quartile as the referent. Immune-related illnesses self-reported at the home visit (May 2011-May 2013) included occurrence of shingles, pneumonia, cold sores, flu, and colds since the Deepwater Horizon oil spill (April 2010). Frequent colds and frequent flu were defined as ≥4 colds and ≥2 episodes of flu since the spill. An aggregated outcome, based on occurrence of any pneumonia, cold sores, flu, and ≥4 colds since the spill, was also examined. We assessed the association of each outcome with ADI using multivariable log-binomial regression adjusting for individual-level demographics, behavioral factors, kids at home, and season of interview completion. RESULTS: We found elevated prevalence ratios (PR) and 95% confidence intervals (CI) for pneumonia associated with ADI in the third (PR: 2.04, 95% CI: 1.04, 4.02) and fourth (PR: 2.00; 95% CI: 1.00, 3.98) quartiles. PRs for frequent colds were also elevated for increasing ADI quartiles, but with confidence intervals including the null value. CONCLUSIONS: The observed associations of frequent colds and pneumonia with increasing neighborhood disadvantage may warrant further research on this topic.

Peripheral Immune Cell Composition is Altered in Women Before and After a Hypertension Diagnosis.

BACKGROUND: The development and consequences of hypertension involve multiple biological systems that may include changes in immune profiles. Whether hypertension is related to peripheral immune cell composition has not been examined in large human cohorts. METHODS: We estimated circulating proportions of 12 leukocyte subsets from the lymphoid and myeloid lineages by deconvolving cell-type-specific DNA methylation data from 4124 women. Hypertension status at baseline was defined by current use of antihypertensive medication and blood pressure measurements while new incident cases were identified during follow-up via annual health questionnaires. RESULTS: Among hypertension-free women at baseline, higher B cell and lower naïve CD4+ helper T cell proportions were associated with subsequent increased hazard of hypertension incidence (B cells; adjusted HR: 1.17 [95% CI: 1.02-1.35]; P=0.03; naïve CD4+ T cell, adjusted HR: 0.88 [95% CI: 0.78-0.99]; P=0.04). Blood pressure measurements at baseline were similarly positively associated with B cells and inversely associated with naïve CD4+ helper T cells. Compared to normotensive women, women with hypertension had higher circulating proportions of neutrophils (adjusted odds ratio: 1.18 [95% CI: 1.07-1.31]; P=0.001) and lower proportions of CD4+ helper T cells (adjusted odds ratio: 0.90 [95% CI: 0.81-1.00] P=0.05), natural killers (adjusted odds ratio: 0.82 [95% CI: 0.74-0.91]; P<0.001), and B cells (adjusted odds ratio: 0.84 [95% CI: 0.74-0.96]; P=0.01). CONCLUSIONS: These observations suggest that shifts in lymphocyte subsets occur before hypertension development, followed by later changes to neutrophils and additional lymphocytes.