Agricultural Health Study Research Articles

Trace Element Concentrations of Arsenic and Selenium in Toenails and Risk of Prostate Cancer among Pesticide Applicators.

Prostate cancer is a common cancer among males in the US, but little is known about its risk factors, including trace elements. The primary aim of this study was to examine prostate cancer and its association with arsenic and selenium in toenails. We conducted a small, nested case-control study of men residing in Iowa within the Agricultural Health Study cohort, where we also collected toenail samples to test for arsenic and other trace elements. Toenail samples were sent for neutron activation analysis aimed at long-lived trace elements, including arsenic. Logistic regression was used to estimate odds ratios (ORs) for trace element exposures and prostate cancer. A total of 66 prostate cancer cases and 173 healthy controls returned questionnaires, over 99% of which included toenail samples. An increased risk was seen for the highest levels of arsenic (OR = 3.4 confidence interval (CI) of 1.3-8.6 and OR = 2.2, 95% CI of 0.9-5.6) and the highest level of selenium (2.0, 95% CI of 1.0-4.0). These data also show detectable levels of over 50% for 14 of 22 elements detected in the toenails. The association seen here with arsenic and prostate cancer further supports ecological studies finding an association with community levels of arsenic and prostate cancer incidence and mortality.

A novel application of Standard Precipitation Index estimates to identify climate-related mortality risks in the Agricultural Health Study

A novel application of Standard Precipitation Index estimates to identify climate-related mortality risks in the Agricultural Health Study

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

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

Adjustment for sparse data bias in odds ratios: Significance to appraisal of risk of diabetes due to occupational trichlorfon insecticide exposure

BackgroundBias away from the null in odds ratios (OR), aggravated by low power, is a well-known phenomenon in statistics (sparse data bias). Such bias increases in presence of selection of “significant” results on the basis of null hypothesis testing (effect size magnification, ESM). ObjectivesWe seek to illustrate these issues and adjust for suspected sparse data bias in the context of a reported more than doubling of the odds of new onset type 2 diabetes in presence of occupational trichlorfon insecticide exposure reported in the Agricultural Health Study. MethodsWe performed ESM analysis on the crude ORs extracted from the contingency table in the published report, which is done by simulating selected OR given a posited true OR. Next, we applied easily accessible methods that adjust for sparse data bias to the extracted contingency tables, including data augmentation, bootstrap, Firth's regression, and Bayesian methods with weakly informative priors. ResultsDuring the ESM analysis, we observed that there was a reasonable chance that a “statistically significant” OR of around 2.5–2.6 would be observed for true OR of 1.2. Adjustment for sparse data bias revealed that Bayesian methods outperformed alternative approaches in terms of yielding more precise inference, while not making unjustified distributional assumptions about estimates of OR. The OR in the original paper of about 2.5–2.6 was reduced on average to OR of 1.9 to 2.2, with 95% (Bayesian) credible intervals that included the null. DiscussionIt is reasonable to adjust ORs for sparse data bias when the reported association has societal importance, because policy must be informed by the least biased estimates of the effect. We think that such adjustment would lead to a more appropriate evaluation of the extent of evidence on the contribution of occupational exposure to trichlorfon pesticide to risk of new onset diabetes.

Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts

One in 3 US adults uses multivitamins (MV), with a primary motivation being disease prevention. In 2022, the US Preventive Services Task Force reviewed data on MV supplementation and mortality from randomized clinical trials and found insufficient evidence for determining benefits or harms owing, in part, to limited follow-up time and external validity. To estimate the association of MV use with mortality risk, accounting for confounding by healthy lifestyle and reverse causation whereby individuals in poor health initiate MV use. This cohort study used data from 3 prospective cohort studies in the US, each with baseline MV use (assessed from 1993 to 2001), and follow-up MV use (assessed from 1998 to 2004), extended duration of follow-up up to 27 years, and extensive characterization of potential confounders. Participants were adults, without a history of cancer or other chronic diseases, who participated in National Institutes of Health-AARP Diet and Health Study (327 732 participants); Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (42 732 participants); or Agricultural Health Study (19 660 participants). Data were analyzed from June 2022 to April 2024. Self-reported MV use. The main outcome was mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. Among 390 124 participants (median [IQR] age, 61.5 [56.7-66.0] years; 216 202 [55.4%] male), 164 762 deaths occurred during follow-up; 159 692 participants (40.9%) were never smokers, and 157 319 participants (40.3%) were college educated. Among daily MV users, 49.3% and 42.0% were female and college educated, compared with 39.3% and 37.9% among nonusers, respectively. In contrast, 11.0% of daily users, compared with 13.0% of nonusers, were current smokers. MV use was not associated with lower all-cause mortality risk in the first (multivariable-adjusted HR, 1.04; 95% CI, 1.02-1.07) or second (multivariable-adjusted HR, 1.04; 95% CI, 0.99-1.08) halves of follow-up. HRs were similar for major causes of death and time-varying analyses. In this cohort study of US adults, MV use was not associated with a mortality benefit. Still, many US adults report using MV to maintain or improve health.

Abstract 837: Carbaryl use and cancer incidence in the agricultural health study - An updated analysis

Abstract Background: Carbaryl is a carbamate insecticide with widespread residential and agricultural uses. Previous epidemiologic investigations, including in the Agricultural Health Study (AHS), have suggested potential associations between carbaryl use and cancer risk. In this analysis, we updated a previous AHS evaluation of carbaryl and cancer risk by incorporating additional exposure information and follow-up time. Methods: The AHS is a prospective cohort study of licensed pesticide applicators in North Carolina (NC) and Iowa (IA). Information on lifetime pesticide use, including carbaryl, was reported on questionnaires at enrollment (1993-1997) and follow-up (1999-2005). We evaluated cancer risks associated with ever-use and intensity-weighted lifetime days (IWLD) of carbaryl use, comparing those who reported use to those who did not. For IWLD, carbaryl exposure was categorized (quartiles, tertiles, or the median) among users, depending on the number of cases. Among 52,625 applicators, 8,713 incident cancers were identified from linkages with state cancer registries through 2014 (NC) or 2017 (IA). We used Poisson regression to estimate risk ratios (RR) and 95% confidence intervals (CI), controlling for confounders, and evaluated lagged exposures. Results: Approximately 50% of applicators reported use of carbaryl. Among cancer cases, 53% reported carbaryl use. Increasing IWLD of carbaryl use was associated with stomach cancer (RRT3=2.15, 95% CI: 1.11-4.15, p-trend=0.02), which persisted across lags up to 15 years. Carbaryl users in the highest quartile of IWLD had an increased risk of leukemia (RRQ4=2.12, 95% CI: 1.05-4.29, p-trend=0.08); this risk remained elevated, though attenuated, when exposure was lagged by 5-years (RRQ4=1.86, 95% CI: 0.91-3.81, p-trend=0.14). Ever-use of carbaryl was also suggestively associated with both esophageal (RR=1.45, 95% CI: 0.98-2.14) and tongue (RR=1.87, 95% CI: 0.93-3.74) cancers. Conclusion: This study provides novel evidence of associations between carbaryl use, leukemia, and stomach cancer, as well as suggestive evidence of elevated risks of esophageal and tongue cancers. With more than 7,000 added cancer cases and up to 14 additional years of follow-up time as compared to a previous analysis in the AHS, we were able evaluate cancer sites not previously examined, making this the largest prospective study of carbaryl and cancer risk to date. Our findings highlight the need for additional studies of this widely used insecticide. Citation Format: Patricia A. Erickson, Gabriella Andreotti, Richard Remigio, Christine G. Parks, Dale P. Sandler, Paul S. Albert, Kathryn H. Barry, Jonathan N. Hofmann, Laura E. Beane Freeman. Carbaryl use and cancer incidence in the agricultural health study - An updated analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 837.

Abstract 834: Farm animal exposures and the oral microbiome in the Agricultural Health Study

Abstract Raising farm animals involves a variety of exposures, including microbes, antimicrobial agents, bioaerosols, and pesticides that may influence the human microbiome. Exposure to farm animals has also been associated with some cancers including lower risk of lung cancer and elevated risks of certain hematologic malignancies, with heterogeneity by animal species. Increasing epidemiologic evidence suggests that changes in the oral microbiome contribute to cancer development. Few human studies have investigated the potential influence of farm animal exposures on the oral microbiome. We investigated associations between farm animal exposures and the oral microbiome in 1245 Iowa and North Carolina farmers and spouses from the Agricultural Health Study. Participants provided information on types and numbers of farm animals raised in telephone interviews close to the time of oral wash sample collection. DNA was extracted from oral wash specimens and analyzed using 16S rRNA gene (V4 region) sequencing. We evaluated associations between farm animal exposures and alpha diversity metrics [e.g., observed amplicon sequence variants (ASVs)] using linear regression and assessed differences in beta diversity metrics (e.g., weighted Unifrac) using permutational multivariate analysis of variance. In addition, we evaluated associations with the presence and relative abundance of specific genera using zero-inflated negative binomial regression. All analyses adjusted for potential confounders (e.g., sex, age, state of residence, smoking). Overall, 63% of participants reported raising any animals, most commonly cattle (46%) and hogs (20%). Raising sheep/goats was associated with lower alpha diversity [e.g., 18 (95% confidence interval: 3-33) fewer observed ASVs compared to not raising sheep/goats], with an exposure-response trend for increasing number of sheep/goats (13 and 24 fewer observed ASVs for 1-29 and ≥30 sheep/goats vs. none, respectively; Ptrend = 0.048). Increasing numbers of hogs and poultry were associated with higher and lower alpha diversity, respectively. Associations were similar after mutual adjustment for other farm animal types. Based on beta diversity analyses, we did not observe statistically significant differences in microbial compositions between participants with and without farm animals. After adjusting for multiple testing, having any farm animal was associated with an increased relative abundance of Porphyromonas, and several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium and Abiotrophia for sheep/goats). To our knowledge, this was the largest investigation of farm animal exposures and the human microbiome to date. Our preliminary findings suggest that animal farming may alter the oral microbiome and provide new insights into the potential role of animal exposures in cancer etiology. Citation Format: Vicky C. Chang, Vaishnavi Purandare, Rashmi Sinha, Gabriella Andreotti, Shilan Li, Xing Hua, Yukiko Yano, Kathryn R. Dalton, Mikyeong Lee, Christine G. Parks, Stephanie J. London, Dale P. Sandler, Mitchell H. Gail, Jianxin Shi, Jonathan N. Hofmann, Christian C. Abnet, Emily Vogtmann, Laura E. Beane Freeman. Farm animal exposures and the oral microbiome in the Agricultural Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 834.

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

BackgroundPesticide 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). ObjectivesWe evaluated use of pesticides and incident IBD in 68,480 eligible pesticide applicators and spouses enrolled in the Agricultural Health Study. MethodsSelf-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. ResultsWe 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). ConclusionsExposure 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.

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. 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. 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. Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (; 95% CI: 0.95, 1.52; ), particularly among those years old (; 95% CI: 1.61, 5.75; ; ). Among applicators years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (; 95% CI: 1.10, 5.38; ). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (: 2.54; 95% CI: 0.97, 6.62; ). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (; 95% CI: 1.45, 6.36; ) and kidney (; 95% CI: 1.15, 2.29; ) cancers. 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.

Plasma protein signatures of adult asthma.

Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma. Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)). Meta-analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75-0.79 in training set; AUC = 0.72, 95% CI = 0.69-0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma-atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis. This first large-scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.

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

BackgroundNitrate 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).ObjectivesWe 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.MethodsWe 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.ResultsWe 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 <median (T3 vs. T1 HR: 2.26, 95%CI: 1.05, 4.86) and with heme iron ≥median (T3 vs. T1 HR: 1.73, 95%CI: 0.89, 3.39).SignificanceESRD incidence was associated with dietary nitrate/nitrite from processed meat among all study participants and with total dietary nitrite among participants with lower vitamin C or higher heme iron intake.Impact statementThere are few well-established environmental risk factors for end-stage renal disease (ESRD), a worldwide public health challenge. Ingestion of nitrate and nitrite, which may lead to endogenous formation of carcinogenic N-nitroso compounds, has been linked to some cancers and chronic diseases. We investigated these exposures in relation to ESRD in an agricultural cohort. ESRD incidence was associated with dietary nitrate/nitrite from processed meat and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. This study provides preliminary evidence that points to dietary nitrite and possibly dietary nitrate intake as a potential contributor to ESRD.

Occupational farm work activities influence workers’ indoor home microbiome

BackgroundFarm 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. ObjectivesWe investigated associations between farm work activities, including specific tasks and pesticide use, and the indoor microbiome in the homes of 468 male farmers. MethodsParticipants 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. ResultsAll 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. DiscussionDifferent 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.

Abstract B126: Disparities in cancer incidence among African American and non-Hispanic White participants in the Agricultural Health Study

Abstract Disparities in the incidence of some cancers (e.g., prostate cancer, multiple myeloma) between African American (AA) and non-Hispanic white (NHW) individuals are well established in the U.S. overall; however, to our knowledge, no previous studies have compared cancer incidence in AA and NHW farming populations. Farmers and their families can face a variety of occupational and environmental exposures that may influence cancer risk, including pesticides, zoonotic diseases, diesel exhaust and air pollution. Given the exposures unique to farming as well as historic discrimination faced by AA farmers, we considered the possibility that racial disparities in cancer incidence might be greater in farmers than in the general population. To explore cancer disparities in farming populations, we conducted an investigation within the Agricultural Health Study (AHS), a prospective cohort of pesticide applicators (mainly malefarmers) and their spouses. Our analyses included 1,505 AA and 27,052 non-Hispanic white (NHW) farmers and spouses from North Carolina who were enrolled in 1993-1997 and followed for cancer incidence through 2014. We examined cancer incidence in AA compared to NHWparticipants, both overall and for specific sites, by estimating hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression models with age as the underlying time metric and adjustment for sex (in analyses of cancer sites that included both sexes) and region (coastal plains, piedmont, and mountains). We identified a total of 4,689 incident cancer cases during follow-up (335 in AA participants and 4,354 in NHW participants). Compared with NHW participants, we observed a higher incidence among AA participants for all cancers (HR = 1.36, 95% CI 1.21 – 1.52) that was apparent among men (n = 272 AA cases; HR 1.45, 95% CI 1.28-1.64) but not among women (n = 63 AA cases; HR 1.12, 95% CI 0.87-1.45). AA participants had a higher incidence of cancers of the prostate (overall: HR 2.01, 95% CI 1.67–2.43; aggressive disease: HR 2.12, 95% CI 1.62–2.79), colon and rectum (HR 1.60, 95% CI 1.15–2.23), larynx (HR 3.52, 95% CI 1.41–8.79), and multiple myeloma (HR = 2.82, 95% CI 1.43 – 5.60). We also observed non-statistically significantly elevated HRs for cancers of the lung, pancreas, kidney, and stomach among AA participants. Findings were similar after excluding participants from the mountain region where few AA participants were enrolled. The observed excesses of cancer incidence overall and for specific cancer sites among AA farmers and spouses compared to their NHW counterparts were generally more apparent than those seen in the overall U.S. population; we plan to further evaluate these disparities through comparisons with statewide cancer incidence rates in North Carolina. Additional efforts are also needed to better understand factors contributing to these disparities, which can inform ways to promote the overall health and well-being of AA farmers and ensure that resources are allocated equitably across all populations. Citation Format: Somayina C. Ezennia, Christine G. Parks, Laura E. Beane-Freeman, Anne Taylor, Gabriella Andreotti, Stella Koutros, Dale P. Sandler, Jonathan N. Hofmann. Disparities in cancer incidence among African American and non-Hispanic White participants in the Agricultural Health Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B126.

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

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. We evaluated the association between lifetime occupational glyphosate use and mosaic loss of chromosome Y (mLOY) as a marker of genotoxicity among male farmers. We analyzed blood-derived DNA from 1,606 farmers 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 of cells (expanded mLOY). 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; (95% CI: 1.00, 3.07), ] but not with overall mLOY; the associations with expanded mLOY were most apparent among older ( years of age) men [ (95% CI: 1.13, 4.67), ], never smokers [ (95% CI: 1.04, 5.21), ], and nonobese men [ (95% CI: 0.99, 4.19), ]. Similar patterns of associations were observed for intensity-weighted lifetime days of glyphosate use. 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.

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

ObjectivesSelf-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. MethodsWe 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. ResultsOver 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). ConclusionThese novel findings suggest that acute, high-level, and clinically impactful pesticide exposures may increase risk of shingles in subsequent years to decades following exposure.

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

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

Ingested nitrate and nitrite and risk of renal cell carcinoma in the Agricultural Health Study

Ingested nitrate and nitrite and risk of renal cell carcinoma in the Agricultural Health Study

Nitrate ingestion from drinking water and dietary sources and risk of brain cancer in the Agricultural Health Study

Nitrate ingestion from drinking water and dietary sources and risk of brain cancer in the Agricultural Health Study

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.

Glyphosate - A Silent, Slow Killer?

Madam, Glyphosate, commercially known as Round Up, is one of the most widely used herbicides and pesticides worldwide. As a synthetic organophosphate compound, it comes in a crystalline, odourless and colourless form. Most of the human exposure to this compound occurs during the process of its manufacturing, formulation and transport. Further exposure may come from the inhaling toxic fumes of nitrogen gas and phosphorus oxides produced when this pesticide undergoes decomposition, when farmers and gardeners use it on their crops, and when individuals come in contact with products containing it as the active ingredient (1). As of right now, there is a multitude of studies that link glyphosate to several morbidities. When a combined 9229 cases of farmers from North America, the European Union and Australia were assessed, glyphosate was directly linked to an increase in the onset of follicular lymphoma (2). It was also associated with allergic and non-allergic wheezing among farm women in the Agricultural Health Study (2005-2010), which focused on farmers in Iowa and North Carolina (3). Additionally, when tested on mice, exposure to glyphosate was found to increase TNFa in the brain and plasma, and the levels of soluble Amyloid Beta in the brain, suggesting a detrimental role to general health. Furthermore, glyphosate was one of the 11 pesticides studied and then found to have a direct correlation with the increase in overall cancer cases in Brazil. (5) Taking into consideration the aforementioned facts, it is vital to regulate the exposure of individuals to glyphosate to reduce the rising rate of morbidities. More guidelines and policies should be formulated to protect the health of individuals involved in glyphosate manufacturing, due to their exposure risk high. Pesticide leching into water sources should also be prevented to ensure that the general population does not end up consume them indirectly.