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Michael C.r. Alavanja - One of the best experts on this subject based on the ideXlab platform.

  • herbicide fumigant and fungicide use and breast cancer risk among farmers wives
    Environmental epidemiology (Philadelphia Pa.), 2020
    Co-Authors: Michael C.r. Alavanja, Aaron Blair, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Emily J Werder, Lawrence S Engel, Jaya M Satagopan, Laura Beane E Freeman
    Abstract:

    Evidence from epidemiologic and laboratory studies relating pesticides to breast cancer risk is inconsistent. Women engaging in Agricultural work or living in Agricultural areas may experience appreciable exposures to a wide range of pesticides, including herbicides, fumigants, and fungicides. Methods We examined exposure to herbicides, fumigants, and fungicides in relation to breast cancer risk among farmers' wives with no prior history of breast cancer in the Agricultural Health Study. Women provided information on pesticide use, demographics, and reproductive history at enrollment (1993-1997) and at a 5-year follow-up interview. We used Cox proportional hazards regression to estimate associations (hazard ratios [HRs] and 95% confidence intervals [CIs]) between the women's and their husbands' self-reported use of individual pesticides and incident breast cancer risk. Results Out of 30,594 women, 38% reported using herbicides, fumigants, or fungicides and 1,081 were diagnosed with breast cancer during a median 15.3 years of follow-up. We found elevated risk in relation to women's ever use of the fungicide benomyl (HR = 1.6; 95% CI = 0.9, 2.7) and the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (HR = 1.6; 95% CI = 0.8, 3.1) and to their husbands' use of the herbicide 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP) (HR = 1.5; 95% CI = 0.9, 2.7). We observed few other chemical associations and little evidence of differential risk by tumor estrogen receptor status or linear exposure-response relationships. Conclusion We did not observe clear excesses between use of specific pesticides and breast cancer risk across exposure metrics, although we did observe elevated risk associated with women's use of benomyl and 2,4,5-T and husbands' use of 2,4,5-TP.

  • abstract 610 a longitudinal investigation of hematologic perturbations among permethrin exposed pesticide applicators in the biomarkers of exposure and effect in agriculture study
    Cancer Research, 2019
    Co-Authors: Joe Shearer, Michael C.r. Alavanja, Charles F Lynch, Gabriella Andreotti, Laura Beane E Freeman, Danping Liu, Jennifer Hamilton, Julie Happel, Jonathan N Hofmann
    Abstract:

    Background: In the Agricultural Health Study, a large prospective cohort of pesticide applicators, high lifetime use of the insecticide permethrin was associated with an increased risk of multiple myeloma. However, the biological mechanisms through which this association occurs remain to be fully understood. Methods: Hematologic perturbations were assessed among 33 permethrin-exposed male pesticide applicators enrolled in the Biomarkers of Exposure and Effect in Agriculture study, a molecular substudy within the Agricultural Health Study. Serial blood samples were collected from each participant coinciding with permethrin use including visits during the offseason, an exposure visit the day after use, and for 27 participants a follow-up visit approximately three weeks after use. Complete blood count with white blood cell differential and lymphocyte subsets were collected at each visit. Linear mixed models were used to assess the relationship between permethrin exposure and hematologic parameters, controlling for potential confounders including season of blood draw, age, body mass index, recent cold/infection, and use of other pesticides. Results: A statistically significant increase in the adjusted mean immature granulocyte count (37%, 95% CI=6%, 76%) was observed the day after permethrin use compared to an offseason visit. Statistically significant (P Conclusions: Altered hematologic parameters could be indicative of disrupted hematopoiesis, providing insights into the potential biologic plausibility of the observed association between permethrin use and multiple myeloma risk among pesticide applicators. Impact/Significance: Given the widespread use of permethrin in both residential and commercial settings, our findings may have public Health implications beyond occupationally exposed pesticide applicators. Citation Format: Joe Shearer, Laura Beane Freeman, Danping Liu, Gabriella Andreotti, Jennifer Hamilton, Julie Happel, Charles Lynch, Michael Alavanja, Jonathan Hofmann. A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 610.

  • glyphosate use and cancer incidence in the Agricultural Health study
    Journal of the National Cancer Institute, 2018
    Co-Authors: Gabriella Andreotti, Jay H Lubin, Charles F Lynch, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Jonathan N Hofmann, Christine G Parks, Anneclaire J De Roos, Michael C.r. Alavanja
    Abstract:

    Background 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.

  • occupational pesticide exposure and subclinical hypothyroidism among male pesticide applicators
    Occupational and Environmental Medicine, 2018
    Co-Authors: Catherine C. Lerro, Dale P Sandler, Stella Koutros, Laura Beane E Freeman, Christine G Parks, Curt T Dellavalle, Muhammad G Kibriya, Briseis Aschebrookkilfoy, Farzana Jasmine, Michael C.r. Alavanja
    Abstract:

    Objectives Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators. Methods Self-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4- Results Higher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (OR Q3 =4.15, 95% CI 1.56 to 11.01, OR Q4 =4.76, 95% CI 1.53 to 14.82, p trend trend =0.01) and lower T4 (p trend =0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: OR Q4 =2.78, 95% CI 1.30 to 5.95, p trend =0.02), higher TSH (p trend =0.04) and anti-TPO positivity (p trend =0.01). The fumigant methyl bromide was inversely associated with TSH (p trend =0.02) and positively associated with T4 (p trend =0.01). Conclusions Our results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators.

  • assessing the potential for bias from nonresponse to a study follow up interview an example from the Agricultural Health study
    American Journal of Epidemiology, 2017
    Co-Authors: Jessica L Rinsky, Michael C.r. Alavanja, Freya Kamel, Laura Beane E Freeman, David B Richardson, Paul K Henneberger, John D Beard, Honglei Chen, Steve Wing, Dale P Sandler
    Abstract:

    Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993-1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005-2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005-2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment.

Jane A Hoppin - One of the best experts on this subject based on the ideXlab platform.

  • animal production insecticide use and self reported symptoms and diagnoses of copd including chronic bronchitis in the Agricultural Health study
    Environment International, 2019
    Co-Authors: Jessica L Rinsky, Laura Beane E Freeman, David B Richardson, Kathleen Kreiss, Leena A Nylanderfrench, Stephanie J London, Paul K Henneberger, Jane A Hoppin
    Abstract:

    Abstract Background Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study. Methods During a 2005–2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms. Conclusion Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for Agricultural workers.

  • occupational exposure to pesticides and the incidence of lung cancer in the Agricultural Health study
    Environmental Health Perspectives, 2016
    Co-Authors: Matthew R Bonner, Kent Thomas, Jane A Hoppin, Charles F Lynch, Aaron Blair, Dale P Sandler, Stella Koutros, Cynthia J. Hines, Laura Beane E Freeman, Michael C.r. Alavanja
    Abstract:

    Background:Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive association...

  • pesticide use and relative leukocyte telomere length in the Agricultural Health study
    PLOS ONE, 2015
    Co-Authors: Gabriella Andreotti, Jane A Hoppin, Jay H Lubin, Aaron Blair, Stella Koutros, Shahinaz M Gadalla, Sharon A Savage, Mirjam Hoxha, Andrea Baccarelli, Dale P Sandler
    Abstract:

    Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.

  • organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health study
    Occupational and Environmental Medicine, 2015
    Co-Authors: Michael C.r. Alavanja, Jane A Hoppin, Aaron Blair, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Gabriella Andreotti, Melissa C Friesen, Jay H Lubin
    Abstract:

    Objectives Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort. Methods At enrolment (1993–1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive Health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa. Results Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43). Conclusions We observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.

  • incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health study an updated analysis
    Occupational and Environmental Medicine, 2015
    Co-Authors: Rena R Jones, Michael C.r. Alavanja, Jane A Hoppin, Jay H Lubin, Aaron Blair, Catherine C. Lerro, Stella Koutros, Francesco Baroneadesi, Sonya L Heltshe, Laura Beane E Freeman
    Abstract:

    Objective Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS. Methods Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993–1997) and follow-up (1998–2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with ≥10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure). Results We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; P trend =0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; P trend =0.08). Kidney cancer (N=94) risks were non-significantly elevated (RR LT days =1.77; 95% CI 0.90 to 3.51; P trend =0.09; RR IW days 1.37; 95% CI 0.64 to 2.92; P trend =0.50), as were risks for aggressive prostate cancer (N=656). Conclusions Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation.

Dale P Sandler - One of the best experts on this subject based on the ideXlab platform.

  • herbicide fumigant and fungicide use and breast cancer risk among farmers wives
    Environmental epidemiology (Philadelphia Pa.), 2020
    Co-Authors: Michael C.r. Alavanja, Aaron Blair, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Emily J Werder, Lawrence S Engel, Jaya M Satagopan, Laura Beane E Freeman
    Abstract:

    Evidence from epidemiologic and laboratory studies relating pesticides to breast cancer risk is inconsistent. Women engaging in Agricultural work or living in Agricultural areas may experience appreciable exposures to a wide range of pesticides, including herbicides, fumigants, and fungicides. Methods We examined exposure to herbicides, fumigants, and fungicides in relation to breast cancer risk among farmers' wives with no prior history of breast cancer in the Agricultural Health Study. Women provided information on pesticide use, demographics, and reproductive history at enrollment (1993-1997) and at a 5-year follow-up interview. We used Cox proportional hazards regression to estimate associations (hazard ratios [HRs] and 95% confidence intervals [CIs]) between the women's and their husbands' self-reported use of individual pesticides and incident breast cancer risk. Results Out of 30,594 women, 38% reported using herbicides, fumigants, or fungicides and 1,081 were diagnosed with breast cancer during a median 15.3 years of follow-up. We found elevated risk in relation to women's ever use of the fungicide benomyl (HR = 1.6; 95% CI = 0.9, 2.7) and the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (HR = 1.6; 95% CI = 0.8, 3.1) and to their husbands' use of the herbicide 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP) (HR = 1.5; 95% CI = 0.9, 2.7). We observed few other chemical associations and little evidence of differential risk by tumor estrogen receptor status or linear exposure-response relationships. Conclusion We did not observe clear excesses between use of specific pesticides and breast cancer risk across exposure metrics, although we did observe elevated risk associated with women's use of benomyl and 2,4,5-T and husbands' use of 2,4,5-TP.

  • alachlor use and cancer incidence in the Agricultural Health study an updated analysis
    Journal of the National Cancer Institute, 2018
    Co-Authors: Catherine C. Lerro, Jay H Lubin, Aaron Blair, Dale P Sandler, Stella Koutros, Gabriella Andreotti, Won Jin Lee, Jonathan N Hofmann, Christine G Parks, Laura Beane E Freeman
    Abstract:

    Background The herbicide alachlor has been widely used in US agriculture since its introduction in 1969. Experimental animal studies show that alachlor causes tumors in vivo; however, few epidemiologic studies have examined associations with human cancer risk. We evaluated alachlor use and cancer incidence in the Agricultural Health Study, updating an earlier analysis that suggested associations with lymphohematopoietic cancers with an additional 540 142 person-years of follow-up and 5113 cancer cases. Methods Pesticide applicators in Iowa and North Carolina reported lifetime alachlor use at enrollment (1993-1997) and follow-up (1999-2005). Exposure was characterized by cumulative intensity-weighted days. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using Poisson regression for incident cancers from enrollment through 2012(NC)/2013(IA). Models adjusted for age, tobacco, alcohol, and other pesticides. All statistical tests are two-sided. Results Among 49 685 applicators, 25 640 (51.6%) used alachlor, with 3534 alachlor-exposed cancers. The relative risks of laryngeal cancer (nexposed = 34) increased in the second (RR = 4.68, 95% CI = 1.95 to 11.23), third (RR = 6.04, 95% CI = 2.44 to 14.99), and fourth quartiles (RR = 7.10, 95% CI = 2.58 to 19.53) of intensity-weighted days of use compared with no use (Ptrend = .001). Risk of myeloid leukemia was elevated, though not statistically significantly so, in the fourth quartile of intensity-weighted days of use (RR = 1.82, 95% CI = 0.85 to 3.87, Ptrend = .17). Conclusions We observed a strong positive association with use of alachlor and laryngeal cancer and a weaker association with myeloid leukemia. The strength and robustness of the association with laryngeal cancer suggests that long-term occupational exposure to alachlor may be a risk factor for laryngeal cancer. This first report requires confirmation.

  • glyphosate use and cancer incidence in the Agricultural Health study
    Journal of the National Cancer Institute, 2018
    Co-Authors: Gabriella Andreotti, Jay H Lubin, Charles F Lynch, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Jonathan N Hofmann, Christine G Parks, Anneclaire J De Roos, Michael C.r. Alavanja
    Abstract:

    Background 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.

  • occupational pesticide exposure and subclinical hypothyroidism among male pesticide applicators
    Occupational and Environmental Medicine, 2018
    Co-Authors: Catherine C. Lerro, Dale P Sandler, Stella Koutros, Laura Beane E Freeman, Christine G Parks, Curt T Dellavalle, Muhammad G Kibriya, Briseis Aschebrookkilfoy, Farzana Jasmine, Michael C.r. Alavanja
    Abstract:

    Objectives Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators. Methods Self-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4- Results Higher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (OR Q3 =4.15, 95% CI 1.56 to 11.01, OR Q4 =4.76, 95% CI 1.53 to 14.82, p trend trend =0.01) and lower T4 (p trend =0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: OR Q4 =2.78, 95% CI 1.30 to 5.95, p trend =0.02), higher TSH (p trend =0.04) and anti-TPO positivity (p trend =0.01). The fumigant methyl bromide was inversely associated with TSH (p trend =0.02) and positively associated with T4 (p trend =0.01). Conclusions Our results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators.

  • assessing the potential for bias from nonresponse to a study follow up interview an example from the Agricultural Health study
    American Journal of Epidemiology, 2017
    Co-Authors: Jessica L Rinsky, Michael C.r. Alavanja, Freya Kamel, Laura Beane E Freeman, David B Richardson, Paul K Henneberger, John D Beard, Honglei Chen, Steve Wing, Dale P Sandler
    Abstract:

    Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993-1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005-2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005-2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment.

Laura Beane E Freeman - One of the best experts on this subject based on the ideXlab platform.

  • herbicide fumigant and fungicide use and breast cancer risk among farmers wives
    Environmental epidemiology (Philadelphia Pa.), 2020
    Co-Authors: Michael C.r. Alavanja, Aaron Blair, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Emily J Werder, Lawrence S Engel, Jaya M Satagopan, Laura Beane E Freeman
    Abstract:

    Evidence from epidemiologic and laboratory studies relating pesticides to breast cancer risk is inconsistent. Women engaging in Agricultural work or living in Agricultural areas may experience appreciable exposures to a wide range of pesticides, including herbicides, fumigants, and fungicides. Methods We examined exposure to herbicides, fumigants, and fungicides in relation to breast cancer risk among farmers' wives with no prior history of breast cancer in the Agricultural Health Study. Women provided information on pesticide use, demographics, and reproductive history at enrollment (1993-1997) and at a 5-year follow-up interview. We used Cox proportional hazards regression to estimate associations (hazard ratios [HRs] and 95% confidence intervals [CIs]) between the women's and their husbands' self-reported use of individual pesticides and incident breast cancer risk. Results Out of 30,594 women, 38% reported using herbicides, fumigants, or fungicides and 1,081 were diagnosed with breast cancer during a median 15.3 years of follow-up. We found elevated risk in relation to women's ever use of the fungicide benomyl (HR = 1.6; 95% CI = 0.9, 2.7) and the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (HR = 1.6; 95% CI = 0.8, 3.1) and to their husbands' use of the herbicide 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP) (HR = 1.5; 95% CI = 0.9, 2.7). We observed few other chemical associations and little evidence of differential risk by tumor estrogen receptor status or linear exposure-response relationships. Conclusion We did not observe clear excesses between use of specific pesticides and breast cancer risk across exposure metrics, although we did observe elevated risk associated with women's use of benomyl and 2,4,5-T and husbands' use of 2,4,5-TP.

  • abstract 610 a longitudinal investigation of hematologic perturbations among permethrin exposed pesticide applicators in the biomarkers of exposure and effect in agriculture study
    Cancer Research, 2019
    Co-Authors: Joe Shearer, Michael C.r. Alavanja, Charles F Lynch, Gabriella Andreotti, Laura Beane E Freeman, Danping Liu, Jennifer Hamilton, Julie Happel, Jonathan N Hofmann
    Abstract:

    Background: In the Agricultural Health Study, a large prospective cohort of pesticide applicators, high lifetime use of the insecticide permethrin was associated with an increased risk of multiple myeloma. However, the biological mechanisms through which this association occurs remain to be fully understood. Methods: Hematologic perturbations were assessed among 33 permethrin-exposed male pesticide applicators enrolled in the Biomarkers of Exposure and Effect in Agriculture study, a molecular substudy within the Agricultural Health Study. Serial blood samples were collected from each participant coinciding with permethrin use including visits during the offseason, an exposure visit the day after use, and for 27 participants a follow-up visit approximately three weeks after use. Complete blood count with white blood cell differential and lymphocyte subsets were collected at each visit. Linear mixed models were used to assess the relationship between permethrin exposure and hematologic parameters, controlling for potential confounders including season of blood draw, age, body mass index, recent cold/infection, and use of other pesticides. Results: A statistically significant increase in the adjusted mean immature granulocyte count (37%, 95% CI=6%, 76%) was observed the day after permethrin use compared to an offseason visit. Statistically significant (P Conclusions: Altered hematologic parameters could be indicative of disrupted hematopoiesis, providing insights into the potential biologic plausibility of the observed association between permethrin use and multiple myeloma risk among pesticide applicators. Impact/Significance: Given the widespread use of permethrin in both residential and commercial settings, our findings may have public Health implications beyond occupationally exposed pesticide applicators. Citation Format: Joe Shearer, Laura Beane Freeman, Danping Liu, Gabriella Andreotti, Jennifer Hamilton, Julie Happel, Charles Lynch, Michael Alavanja, Jonathan Hofmann. A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 610.

  • animal production insecticide use and self reported symptoms and diagnoses of copd including chronic bronchitis in the Agricultural Health study
    Environment International, 2019
    Co-Authors: Jessica L Rinsky, Laura Beane E Freeman, David B Richardson, Kathleen Kreiss, Leena A Nylanderfrench, Stephanie J London, Paul K Henneberger, Jane A Hoppin
    Abstract:

    Abstract Background Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study. Methods During a 2005–2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms. Conclusion Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for Agricultural workers.

  • alachlor use and cancer incidence in the Agricultural Health study an updated analysis
    Journal of the National Cancer Institute, 2018
    Co-Authors: Catherine C. Lerro, Jay H Lubin, Aaron Blair, Dale P Sandler, Stella Koutros, Gabriella Andreotti, Won Jin Lee, Jonathan N Hofmann, Christine G Parks, Laura Beane E Freeman
    Abstract:

    Background The herbicide alachlor has been widely used in US agriculture since its introduction in 1969. Experimental animal studies show that alachlor causes tumors in vivo; however, few epidemiologic studies have examined associations with human cancer risk. We evaluated alachlor use and cancer incidence in the Agricultural Health Study, updating an earlier analysis that suggested associations with lymphohematopoietic cancers with an additional 540 142 person-years of follow-up and 5113 cancer cases. Methods Pesticide applicators in Iowa and North Carolina reported lifetime alachlor use at enrollment (1993-1997) and follow-up (1999-2005). Exposure was characterized by cumulative intensity-weighted days. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using Poisson regression for incident cancers from enrollment through 2012(NC)/2013(IA). Models adjusted for age, tobacco, alcohol, and other pesticides. All statistical tests are two-sided. Results Among 49 685 applicators, 25 640 (51.6%) used alachlor, with 3534 alachlor-exposed cancers. The relative risks of laryngeal cancer (nexposed = 34) increased in the second (RR = 4.68, 95% CI = 1.95 to 11.23), third (RR = 6.04, 95% CI = 2.44 to 14.99), and fourth quartiles (RR = 7.10, 95% CI = 2.58 to 19.53) of intensity-weighted days of use compared with no use (Ptrend = .001). Risk of myeloid leukemia was elevated, though not statistically significantly so, in the fourth quartile of intensity-weighted days of use (RR = 1.82, 95% CI = 0.85 to 3.87, Ptrend = .17). Conclusions We observed a strong positive association with use of alachlor and laryngeal cancer and a weaker association with myeloid leukemia. The strength and robustness of the association with laryngeal cancer suggests that long-term occupational exposure to alachlor may be a risk factor for laryngeal cancer. This first report requires confirmation.

  • occupational pesticide exposure and subclinical hypothyroidism among male pesticide applicators
    Occupational and Environmental Medicine, 2018
    Co-Authors: Catherine C. Lerro, Dale P Sandler, Stella Koutros, Laura Beane E Freeman, Christine G Parks, Curt T Dellavalle, Muhammad G Kibriya, Briseis Aschebrookkilfoy, Farzana Jasmine, Michael C.r. Alavanja
    Abstract:

    Objectives Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators. Methods Self-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4- Results Higher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (OR Q3 =4.15, 95% CI 1.56 to 11.01, OR Q4 =4.76, 95% CI 1.53 to 14.82, p trend trend =0.01) and lower T4 (p trend =0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: OR Q4 =2.78, 95% CI 1.30 to 5.95, p trend =0.02), higher TSH (p trend =0.04) and anti-TPO positivity (p trend =0.01). The fumigant methyl bromide was inversely associated with TSH (p trend =0.02) and positively associated with T4 (p trend =0.01). Conclusions Our results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators.

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  • herbicide fumigant and fungicide use and breast cancer risk among farmers wives
    Environmental epidemiology (Philadelphia Pa.), 2020
    Co-Authors: Michael C.r. Alavanja, Aaron Blair, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Emily J Werder, Lawrence S Engel, Jaya M Satagopan, Laura Beane E Freeman
    Abstract:

    Evidence from epidemiologic and laboratory studies relating pesticides to breast cancer risk is inconsistent. Women engaging in Agricultural work or living in Agricultural areas may experience appreciable exposures to a wide range of pesticides, including herbicides, fumigants, and fungicides. Methods We examined exposure to herbicides, fumigants, and fungicides in relation to breast cancer risk among farmers' wives with no prior history of breast cancer in the Agricultural Health Study. Women provided information on pesticide use, demographics, and reproductive history at enrollment (1993-1997) and at a 5-year follow-up interview. We used Cox proportional hazards regression to estimate associations (hazard ratios [HRs] and 95% confidence intervals [CIs]) between the women's and their husbands' self-reported use of individual pesticides and incident breast cancer risk. Results Out of 30,594 women, 38% reported using herbicides, fumigants, or fungicides and 1,081 were diagnosed with breast cancer during a median 15.3 years of follow-up. We found elevated risk in relation to women's ever use of the fungicide benomyl (HR = 1.6; 95% CI = 0.9, 2.7) and the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (HR = 1.6; 95% CI = 0.8, 3.1) and to their husbands' use of the herbicide 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP) (HR = 1.5; 95% CI = 0.9, 2.7). We observed few other chemical associations and little evidence of differential risk by tumor estrogen receptor status or linear exposure-response relationships. Conclusion We did not observe clear excesses between use of specific pesticides and breast cancer risk across exposure metrics, although we did observe elevated risk associated with women's use of benomyl and 2,4,5-T and husbands' use of 2,4,5-TP.

  • cancer incidence in the Agricultural Health study farmers is the lung cancer deficit due to endotoxin
    ISEE Conference Abstracts, 2018
    Co-Authors: Catherine C. Lerro, Jay H Lubin, Charles F Lynch, Aaron Blair, Stella Koutros, Gabriella Andreotti, Christine G Parks, Lydia M. Louis, Dale Sandler, Paul S Albert
    Abstract:

    Compared to the general population, Agricultural populations have lower incidence of overall cancer, in part driven by lower lung cancer rates. This deficit is partially due to lifestyle factors (e...

  • alachlor use and cancer incidence in the Agricultural Health study an updated analysis
    Journal of the National Cancer Institute, 2018
    Co-Authors: Catherine C. Lerro, Jay H Lubin, Aaron Blair, Dale P Sandler, Stella Koutros, Gabriella Andreotti, Won Jin Lee, Jonathan N Hofmann, Christine G Parks, Laura Beane E Freeman
    Abstract:

    Background The herbicide alachlor has been widely used in US agriculture since its introduction in 1969. Experimental animal studies show that alachlor causes tumors in vivo; however, few epidemiologic studies have examined associations with human cancer risk. We evaluated alachlor use and cancer incidence in the Agricultural Health Study, updating an earlier analysis that suggested associations with lymphohematopoietic cancers with an additional 540 142 person-years of follow-up and 5113 cancer cases. Methods Pesticide applicators in Iowa and North Carolina reported lifetime alachlor use at enrollment (1993-1997) and follow-up (1999-2005). Exposure was characterized by cumulative intensity-weighted days. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using Poisson regression for incident cancers from enrollment through 2012(NC)/2013(IA). Models adjusted for age, tobacco, alcohol, and other pesticides. All statistical tests are two-sided. Results Among 49 685 applicators, 25 640 (51.6%) used alachlor, with 3534 alachlor-exposed cancers. The relative risks of laryngeal cancer (nexposed = 34) increased in the second (RR = 4.68, 95% CI = 1.95 to 11.23), third (RR = 6.04, 95% CI = 2.44 to 14.99), and fourth quartiles (RR = 7.10, 95% CI = 2.58 to 19.53) of intensity-weighted days of use compared with no use (Ptrend = .001). Risk of myeloid leukemia was elevated, though not statistically significantly so, in the fourth quartile of intensity-weighted days of use (RR = 1.82, 95% CI = 0.85 to 3.87, Ptrend = .17). Conclusions We observed a strong positive association with use of alachlor and laryngeal cancer and a weaker association with myeloid leukemia. The strength and robustness of the association with laryngeal cancer suggests that long-term occupational exposure to alachlor may be a risk factor for laryngeal cancer. This first report requires confirmation.

  • glyphosate use and cancer incidence in the Agricultural Health study
    Journal of the National Cancer Institute, 2018
    Co-Authors: Gabriella Andreotti, Jay H Lubin, Charles F Lynch, Dale P Sandler, Catherine C. Lerro, Stella Koutros, Jonathan N Hofmann, Christine G Parks, Anneclaire J De Roos, Michael C.r. Alavanja
    Abstract:

    Background 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.

  • occupational pesticide exposure and subclinical hypothyroidism among male pesticide applicators
    Occupational and Environmental Medicine, 2018
    Co-Authors: Catherine C. Lerro, Dale P Sandler, Stella Koutros, Laura Beane E Freeman, Christine G Parks, Curt T Dellavalle, Muhammad G Kibriya, Briseis Aschebrookkilfoy, Farzana Jasmine, Michael C.r. Alavanja
    Abstract:

    Objectives Animal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators. Methods Self-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4- Results Higher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (OR Q3 =4.15, 95% CI 1.56 to 11.01, OR Q4 =4.76, 95% CI 1.53 to 14.82, p trend trend =0.01) and lower T4 (p trend =0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: OR Q4 =2.78, 95% CI 1.30 to 5.95, p trend =0.02), higher TSH (p trend =0.04) and anti-TPO positivity (p trend =0.01). The fumigant methyl bromide was inversely associated with TSH (p trend =0.02) and positively associated with T4 (p trend =0.01). Conclusions Our results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators.