Glyphosate is the most commonly used herbicide worldwide, with both residential and agricultural uses. In 2015, the International Agency for Research on Cancer classified glyphosate as "probably ...carcinogenic to humans," noting strong mechanistic evidence and positive associations for non-Hodgkin lymphoma (NHL) in some epidemiologic studies. A previous evaluation in the Agricultural Health Study (AHS) with follow-up through 2001 found no statistically significant associations with glyphosate use and cancer at any site.
The AHS is a prospective cohort of licensed pesticide applicators from North Carolina and Iowa. Here, we updated the previous evaluation of glyphosate with cancer incidence from registry linkages through 2012 (North Carolina)/2013 (Iowa). Lifetime days and intensity-weighted lifetime days of glyphosate use were based on self-reported information from enrollment (1993-1997) and follow-up questionnaires (1999-2005). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounders, including use of other pesticides. All statistical tests were two-sided.
Among 54 251 applicators, 44 932 (82.8%) used glyphosate, including 5779 incident cancer cases (79.3% of all cases). In unlagged analyses, glyphosate was not statistically significantly associated with cancer at any site. However, among applicators in the highest exposure quartile, there was an increased risk of acute myeloid leukemia (AML) compared with never users (RR = 2.44, 95% CI = 0.94 to 6.32, Ptrend = .11), though this association was not statistically significant. Results for AML were similar with a five-year (RRQuartile 4 = 2.32, 95% CI = 0.98 to 5.51, Ptrend = .07) and 20-year exposure lag (RRTertile 3 = 2.04, 95% CI = 1.05 to 3.97, Ptrend = .04).
In this large, prospective cohort study, no association was apparent between glyphosate and any solid tumors or lymphoid malignancies overall, including NHL and its subtypes. There was some evidence of increased risk of AML among the highest exposed group that requires confirmation.
Highlights • Telomere shortening predicts numerous diseases and may be a biomarker of aging. • Past research suggests stress may be related to telomere shortening. • We find a very small pooled ...correlation between increased stress and short telomeres. • Future work should address possible publication bias and improve stress measurement.
Systemic lupus erythematosus (SLE) is a multisystem disease with a complex etiology. Its risk is higher among women, racial and ethnic minorities, and individuals with a family history of SLE or ...related autoimmune diseases. It is believed that genetic factors interact with environmental exposures throughout the lifespan to influence susceptibility to developing SLE. The strongest epidemiologic evidence exists for increased risk of SLE associated with exposure to crystalline silica, current cigarette smoking, use of oral contraceptives, and postmenopausal hormone replacement therapy, while there is an inverse association with alcohol use. Emerging research results suggest possible associations of SLE risk with exposure to solvents, residential and agricultural pesticides, heavy metals, and air pollution. Ultraviolet light, certain infections, and vaccinations have also been hypothesized to be related to SLE risk. Mechanisms linking environmental exposures and SLE include epigenetic modifications resulting from exposures, increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal effects. Research needs to include new studies of environmental risk factors for SLE in general, with a focus on lifetime exposure assessment. In addition, studies in susceptible subgroups, such as family members, studies based on genetic risk profiles, and studies in individuals with evidence of pre-clinical autoimmunity based on the detection of specific auto-antibodies are also required. Understanding the role of environmental exposures in the development of SLE may help identify modifiable risk factors and potential etiological mechanisms.
Objective
Growing evidence suggests increasing frequencies of autoimmunity and certain autoimmune diseases, but findings are limited by the lack of systematic data and evolving approaches and ...definitions. This study was undertaken to investigate whether the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, changed over a recent 25‐year span in the US.
Methods
Serum ANA were measured by standard indirect immunofluorescence assays on HEp‐2 cells in 14,211 participants age ≥12 years from the National Health and Nutrition Examination Survey, with approximately one‐third from each of 3 time periods: 1988–1991, 1999–2004, and 2011–2012. We used logistic regression adjusted for sex, age, race/ethnicity, and survey design variables to estimate changes in ANA prevalence across the time periods.
Results
The prevalence of ANA was 11.0% (95% confidence interval 95% CI 9.7–12.6%) in 1988–1991, 11.5% (95% CI 10.3–12.8%) in 1999–2004, and 15.9% (95% CI 14.3–17.6%) in 2011–2012 (P for trend < 0.0001), which corresponds to ~22 million, ~27 million, and ~41 million affected individuals, respectively. Among adolescents age 12–19 years, ANA prevalence increased substantially, with odds ratios (ORs) of 2.02 (95% CI 1.16–3.53) and 2.88 (95% CI 1.64–5.04) in the second and third time periods relative to the first (P for trend < 0.0001). ANA prevalence increased in both sexes (especially in men), older adults (age ≥50 years), and non‐Hispanic whites. These increases in ANA prevalence were not explained by concurrent trends in weight (obesity/overweight), smoking exposure, or alcohol consumption.
Conclusion
The prevalence of ANA in the US has increased considerably in recent years. Additional studies to determine factors underlying these increases in ANA prevalence could elucidate causes of autoimmunity and enable the development of preventative measures.
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.
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.
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;
=0.03; naïve CD4+ T cell, adjusted HR: 0.88 95% CI: 0.78-0.99;
=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;
=0.001) and lower proportions of CD4+ helper T cells (adjusted odds ratio: 0.90 95% CI: 0.81-1.00
=0.05), natural killers (adjusted odds ratio: 0.82 95% CI: 0.74-0.91;
<0.001), and B cells (adjusted odds ratio: 0.84 95% CI: 0.74-0.96;
=0.01).
These observations suggest that shifts in lymphocyte subsets occur before hypertension development, followed by later changes to neutrophils and additional lymphocytes.
Purpose: Physical activity has been associated with reduced breast cancer risk, but studies of occupational activity have produced inconsistent results. The purpose of this study was to evaluate the ...relationship between occupational physical activity and breast cancer in a prospective study of women with a family history of breast cancer. Methods: We studied breast cancer risk in 47,649 Sister Study participants with an occupational history. Information on occupational activity and breast cancer risk factors was collected during baseline interviews (2004–2009). Physical activity at each job was self-reported and categorized as mostly sitting, sitting and standing equally, mostly standing, and active. Multivariable Cox proportional hazards regression was used to evaluate associations between lifetime occupational activity and incident breast cancer, after adjusting for established risk factors and recreational activity. Results: During follow-up, a total of 1,798 breast cancer diagnoses were reported. Compared with women who did not spend any time in active jobs, women who spent a high proportion (≥75 %) of their working years in active jobs had a reduced risk of breast cancer (HR 0.72; 95 % CI 0.52–0.98). Associations were strongest among overweight (HR 0.64; 95 % CI 0.42–0.98) and postmenopausal (HR 0.67; 95 % CI 0.45–0.98) women. Conclusions: Occupational activity was associated with a reduced risk of breast cancer. Occupational activity is a domain of physical activity that should be further examined in studies of postmenopausal breast cancer risk. Additional research is necessary to better understand the mechanisms underlying the relationships between occupational activity, body size, and breast cancer.
Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease, whose etiology includes both genetic and environmental factors. Individual genetic risk factors likely only account for ...about one‐third of observed heritability among individuals with a family history of SLE. A large portion of the remaining risk may be attributable to environmental exposures and gene–environment interactions. This review focuses on SLE risk associated with environmental factors, ranging from chemical and physical environmental exposures to lifestyle behaviors, with the weight of evidence supporting positive associations between SLE and occupational exposure to crystalline silica, current smoking, and exogenous estrogens (e.g., oral contraceptives and postmenopausal hormones). Other risk factors may include lifestyle behaviors (e.g., dietary intake and sleep) and other exposures (e.g., ultraviolet UV radiation, air pollution, solvents, pesticides, vaccines and medications, and infections). Alcohol use may be associated with decreased SLE risk. We also describe the more limited body of knowledge on gene–environment interactions and SLE risk, including IL‐10, ESR1, IL‐33, ITGAM, and NAT2 and observed interactions with smoking, UV exposure, and alcohol. Understanding genetic and environmental risk factors for SLE, and how they may interact, can help to elucidate SLE pathogenesis and its clinical heterogeneity. Ultimately, this knowledge may facilitate the development of preventive interventions that address modifiable risk factors in susceptible individuals and vulnerable populations.
•Many pesticides are known to have thyroid-disrupting properties.•Prospective study of farmers to evaluate 44 pesticides and thyroid cancer.•Thyroid cancer associated with metalaxyl, lindane, and ...carbaryl (inverse).•First study to comprehensively evaluate occupational pesticides and thyroid cancer.
Many pesticides are known to have thyroid-disrupting properties. However, few studies have evaluated the association between specific pesticide ingredients and risk of thyroid cancer. We investigated self-reported pesticide use and incident thyroid cancer in the Agricultural Health Study (AHS), a large cohort of occupationally-exposed male pesticide applicators.
The AHS is a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. At enrollment (1993–1997) and follow-up (1999–2005), participants reported use of 50 pesticides. We characterized exposure as ever use (44 pesticides with ≥5 exposed cases) and by cumulative intensity-weighted lifetime days (22 pesticides with ≥10 exposed cases), a metric that accounts for factors that influence exposure. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression for incident thyroid (n = 85 cases) cancer among male participants using follow-up through 2014/2015.
Use of the fungicide metalaxyl (HR = 2.03, CI:1.16–3.52) and the organochlorine insecticide lindane (HR = 1.74, CI:1.06–2.84) was associated with increased risk of thyroid cancer. The herbicide chlorimuron-ethyl was inversely associated with risk when we restricted to papillary thyroid cancer, the most common subtype (HR = 0.52, CI:0.28–0.96). High use of the insecticide carbaryl (>median intensity-weighted days) was inversely associated with thyroid cancer (HR = 0.20, CI:0.08–0.53, ptrend = 0.001).
In this large cohort study, we observed increased risk of thyroid cancer associated with use of metalaxyl and lindane, and an inverse association with carbaryl. More work is needed to understand the potential role of these chemicals in thyroid carcinogenesis.
In epidemiologic studies where physician-based case adjudication is not feasible, Parkinson's disease (PD) case ascertainment is often limited to self-reports which may not be accurate. We evaluated ...strategies to identify PD cases in the Agricultural Health Study (AHS).
Doctor-diagnosed PD was self-reported on all cohort-wide surveys; potential cases were also identified from death certificates. Follow-up surveys asked about PD-related motor and non-motor symptoms. For PD confirmation, we collected additional diagnosis, symptom, and treatment data from 510 potential PD cases or their proxy (65% of those contacted) in a supplemental screener and obtained medical records for a subset (n = 65). We classified PD cases using established criteria and screener data.
Of 510 potential PD cases, 75% were considered "probable" or "possible"; this proportion increased among participants diagnosed by a specialist (81.2%), taking PD medication (85.2%), or reporting ≥5 motor symptoms (86.8%) in a regular AHS survey. Of those with medical records, 93% (57 of 61) of probable or possible PD was confirmed. Never-smoking and non-motor and motor symptoms reported in prior AHS surveys were more common with probable/possible PD than unconfirmed PD.
In this retrospective PD case ascertainment effort, we found that PD self-report with information on motor symptoms or medications may be a reasonable alternative for identifying PD cases when physician exam is not feasible. Because of intervening mortality, screeners could not be obtained from about one-third of those contacted. Thus, findings warrant replication.