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The article discusses a study conducted to evaluate the occurrence of High Pesticide Exposure Events (HPEEs) in the Agricultural Health Study (AHS), which is designed to identify agricultural exposures, particularly pesticides, associated with cancer and other diseases in North Carolina or Iowa. It has been informed that the study examined risk of HPEEs during 1993-1997 and 1999-2003 among participants by calculating hazard rate ratios.

This article discusses on the personal protective equipment use and fungicide application practices among orchard farmers in the agricultural health study. Seventy-four private orchard applicators participated in the Orchard Fungicide Exposure Study in 2002-2003. During 144 days of observation, information was obtained on chemicals applied and applicator mixing, personal protective, application, and hygiene practices. Air blast was the most frequent application method used and rubber gloves were the most frequently worn protective equipment.

Discuses results of a study which investigated differences in pesticide contamination and exposure factors between 25 farm homes and 25 non-farm homes. Number of houses using residential pesticides in the home, on the lawn and in the garden; Crop and pesticide spraying demographics; Active ingredients applied by farmers to corn and soybeans.

Objectives: To explore whether mortality from multiple sclerosis is negatively associated with exposure to sunlight.Methods: Two case-control studies based on death certificates were conducted for mortality from multiple sclerosis and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from multiple sclerosis between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded cancer and certain neurological deaths. The effects of occupational exposure to sunlight were assessed among subjects with usual occupations requiring substantial activity, so as to exclude those whose indoor jobs resulted from disabilities subsequent to the onset of the disease. Multiple logistic regression analyses were applied, with adjustment for age, sex, race, and socioeconomic status.Results: Unlike mortality from skin cancer, mortality from multiple sclerosis was negatively associated with residential exposure to sunlight (odds ratio (OR)=0.53 (multiple sclerosis) and OR=1.24 (skin cancer)). Odds ratios for the highest occupational exposure to sunlight were 0.74 (95% confidence interval (95% CI) 0.61 to 0.89) for mortality from multiple sclerosis, compared with 1.21 (1.09 to 1.34) for mortality from non-melanoma skin cancer. The OR was 0.24 for the combined effect of the highest levels of residential and occupational exposure to sunlight on multiple sclerosis, compared with an OR of 1.38 for skin cancer.Conclusions: In this exploratory study, mortality from multiple sclerosis, unlike mortality from skin cancer, was negatively associated with both residential and occupational exposure to sunlight. [ABSTRACT FROM AUTHOR]

Objective: Some epidemiological studies suggest that diets high in fat, saturated fat, or cholesterol are associated with increased risk of lung cancer. Since meat consumption is correlated with the intake of saturated fat and cholesterol, we investigated the role of meat intake and cooking practices in relation to lung cancer risk.Methods: A population-based case-control study of both non-smoking and smoking women was conducted in Missouri. A 100-item food frequency questionnaire (FFQ) with detailed questions on meat consumption was completed by 593 cases and 623 frequency matched controls. We estimated quantity of meat eaten (grams/day) according to cooking method, and doneness level. Odds ratios (ORs) and 95% confidence intervals (C.I.s) were calculated using logistic regression. Multivariate models included age, packyears of smoking, body mass index (BMI, kg/m2), education, and intake of calories, fat, fruit/fruit juices, and vegetables.Results: When comparing 90th and 10th percentiles, lung cancer risk increased for total meat consumption (OR = 1.6, C.I. 1.1-2.4), red meat (OR = 1.8, C.I., 1.2-2.7), well-done red meat (OR = 1.5, C.I.s, 1.1-2.1) and fried red meat (OR = 1.5, C.I., 1.1-2.0). The odds ratios for 5th vs. 1st quintiles using the categorical variable for well-done red meat and fried red meat were essentially the same as reported above; however, the increase in risk was associated mainly with the 5th quintile. The ORs for a 10-gram increase in consumption were, 1.04 for total meat, 1.06 for red meat, 1.08 for well done red meat, and 1.09 for fried red meat.Conclusions: Consumption of red meat, especially fried and/or well-done red meat, was associated with increased risk of lung cancer. [ABSTRACT FROM AUTHOR]

In a population-based case-control study of women in Missouri (United States), most of whom were smokers, we obtained information on adult diet to evaluate the effects of dietary fats in relation to lung cancer risk. All newly diagnosed, primary lung cancer cases among women 35 to 84 years of age reported to the Missouri Cancer Registry from 1 January 1993 to 31 January 1994 were invited to participate, as were population-based controls. The analysis focused on interviews obtained from 624 controls and 587 cases. In-person interviews were obtained from 99.0 percent of controls and 60.6 percent of cases. Age and energy-adjusted relative risks suggested a direct relation between risk of lung cancer and intake of dietary fats (e.g., total fat, saturated fat) and frequency of meat consumption. After adjusting for confounders, dietary fats were no longer associated with risk, but the adverse effect of frequent consumption of meat persisted. Risk was elevated about 90 percent (95 percent confidence interval = 1.2-3.0) among women in the highest quintile of red meat intake compared with those in the lowest quintile. Risk estimates associated with red meat consumption, however, were dependent on interview status; the effect was restricted to cases whose dietary information was provided by proxy. In summary, after adjusting for potential confounders and removing data obtained from proxy respondents, dietary fats and consumption of red meat were not associated with lung cancer risk among women in Missouri. [ABSTRACT FROM AUTHOR]

Despite the growing number of studies on the health effects of passive smoke exposure, few data exist on the quality of questionnaire data on passive smoking. To measure the reliability of passive smoking histories, re-interviews were conducted for 110 subjects (37 cases and 73 controls) as part of a larger study of lung cancer among non-smoking women in Missouri. Agreement was high both for parental smoking status (94% concordance; kappa = 0.82) and for spousal smoking status (84% concordance; kappa = 0.67). Concordance also was relatively high for cigarette pack-years of exposure due to the parents or spouse. Reliability tended to be somewhat higher among controls than among cases, and for exposure due to a parent or spouse than for that due to other household members. Questions on the perceived harmfulness of passive smoke exposure showed no differences between cases and controls. These findings indicate a high degree of repeatability in responses regarding passive smoking, but also suggest the potential for misclassification of passive smoke exposure status, the desirability of standardized questions on passive smoking, and the need for additional studies of reliability and validity. [ABSTRACT FROM AUTHOR]

Abstract Background Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. Methods/Design We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. Discussion EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.

Objective: Colorectal cancer (CRC) has a significant role in cancer-related mortality. Colonoscopy, combined with adenoma removal, has proven effective in reducing CRC incidence. However, suboptimal colonoscopy quality often leads to missed polyps. The impact of artificial intelligence (AI) on adenoma and polyp detection rate (ADR, PDR) is yet to be established., Design: We conducted a randomised controlled trial at Sahlgrenska University Hospital in Sweden. Patients underwent colonoscopy with or without the assistance of AI (AI-C or conventional colonoscopy (CC)). Examinations were performed with two different AI systems, that is, Fujifilm CADEye and Medtronic GI Genius. The primary outcome was ADR., Results: Among 286 patients, 240 underwent analysis (average age: 66 years). The ADR was 42% for all patients, and no significant difference emerged between AI-C and CC groups (41% vs 43%). The overall PDR was 61%, with a trend towards higher PDR in the AI-C group. Subgroup analysis revealed higher detection rates for sessile serrated lesions (SSL) with AI assistance (AI-C 22%, CC 11%, p=0.004). No difference was noticed in the detection of polyps or adenomas per colonoscopy. Examinations were most often performed by experienced endoscopists, 78% (n=86 AI-C, 100 CC)., Conclusion: Amidst the ongoing AI integration, ADR did not improve with AI. Particularly noteworthy is the enhanced detection rates for SSL by AI assistance, especially since they pose a risk for postcolonoscopy CRC. The integration of AI into standard colonoscopy practice warrants further investigation and the development of improved software might be necessary before enforcing its mandatory implementation., Trial Registration Number: NCT05178095., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination., Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-γ (IFN-γ) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-γ was quantified before and after the 1 st and 2 nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG)., Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1 st ( p < 0.001 vs. controls) and 2 nd ( p < 0.001) vaccination. Sixty-eight percent of patients lacked detectable S1-specific T-cell reactivity after the 1 st vaccination vs. 19% in controls (odds ratio 0.11, 95% CI 0.03-0.48, p = 0.003) and 36% remained devoid of reactivity after the 2 nd vaccination vs. 6% in controls (odds ratio 0.12, 95% CI 0.03-0.59, p = 0.009). T-cell reactivity in cirrhosis remained significantly impaired after correction for potential confounders in multivariable analysis. Advanced cirrhosis (Child-Pugh class B) was associated with absent or lower T-cell responses ( p < 0.05 vs. Child-Pugh class A). The deficiency of T-cell reactivity was paralleled by lower levels of anti-RBD-S1 IgG after the 1 st ( p < 0.001 vs. controls) and 2 nd ( p < 0.05) vaccination., Conclusions: Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures., Clinical Trial Registration: EudraCT 2021-000349-42., Lay Summary: T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Background: Olfactory impairment (OI) is common among older adults and independently predicts all-cause mortality and the risk of several major neurodegenerative diseases. Pesticide exposure may impair olfaction, but empirical evidence is lacking., Objective: We aimed to examine high pesticide exposure events (HPEEs) in relation to self-reported OI in participants in the Agricultural Health Study (AHS)., Methods: We conducted multivariable logistic regression to examine the associations between HPEEs reported at enrollment (1993–1997) and self-reported OI at the latest AHS follow-up (2013–2015) among 11,232 farmers, using farmers without HPEEs as the reference or unexposed group., Results: A total of 1,186 (10.6%) farmers reported OI. A history of HPEEs reported at enrollment was associated with a higher likelihood of reporting OI two decades later {odds ratio [Formula: see text] [95% confidence interval (CI): 1.28, 1.73]}. In the analyses on the HPEE involving the highest exposure, the association appears to be stronger when there was a [Formula: see text] delay between HPEE and washing with soap and water [e.g., [Formula: see text] (95% CI: 1.48, 2.89) for 4-6 h vs. [Formula: see text] (95% CI: 1.11, 1.75) for [Formula: see text]]. Further, significant associations were observed both for HPEEs involving the respiratory or digestive tract [[Formula: see text] (95% CI: 1.22, 1.92)] and dermal contact [[Formula: see text] (95% CI: 1.22, 1.78)]. Finally, we found significant associations with several specific pesticides involved in the highest exposed HPEEs, including two organochlorine insecticides (DDT and lindane) and four herbicides (alachlor, metolachlor, 2,4-D, and pendimethalin). HPEEs that occurred after enrollment were also associated with OI development., Conclusions: HPEEs may cause long-lasting olfactory deficit. Future studies should confirm these findings with objectively assessed OI and also investigate potential mechanisms. https://doi.org/10.1289/EHP3713.

Introduction: Dream enacting behavior (DEB) during REM sleep is a characteristic feature of REM sleep behavior disorder (RBD), the most specific prodromal symptom for Parkinson's disease (PD) and related synucleinopathies., Methods: We screened for DEB among 20,591 male farmers in 2013-2015 using a validated question, and examined its association with pesticide uses and other potential risk factors reported about twenty years ago in 1993-1997. We reported odds ratios (OR) and 95% confidence intervals (CI) from multivariable logistic regression models., Results: A total of 1623 (7.9%) farmers reported having had DEB. Farmers with DEB were more likely to report other nonmotor and motor symptoms of PD with age-adjusted ORs ranging from 1.9 to 3.0. DEB prevalence varied little by age, but was significantly associated with current smoking (adjusted OR: 1.4, 95%CI: 1.2, 1.6), daily alcohol drinking (OR: 1.4, 95%CI: 1.1, 1.6), a history of head injury (OR: 1.3, 95%CI: 1.2, 1.5), and being married (OR: 1.4, 95%CI: 1.1, 1.7). We identified significant associations for several pesticides, especially cyclodiene organochlorines and pyrethroids, with adjusted ORs ranging from 1.2 to 1.5. The results were similar after excluding PD cases or when farmers with at least three DEB episodes in life were considered as DEB cases., Conclusions: This study suggests that DEB are not rare among male farmers. Findings on potential risk factors for DEB are intriguing, and given the close link between RBD and PD, these associations should be further investigated., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: Few studies have evaluated the presence of multiple nonmotor symptoms (NMS) in relation to Parkinson disease (PD). Therefore, we examined cross-sectional associations between individual and multiple NMS and PD in the Agricultural Health Study., Methods: 20,473 male farmers and 16,259 female spouses provided information on six NMS (reduced sense of smell, dream-enacting behavior, daytime sleepiness, infrequent bowel movement, depression, and anxiety) in the cohort's 2013-2015 follow-up survey. 191 men and 68 women reported physician-diagnosed PD. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models separately by sex., Results: NMS were each associated with PD, with the strongest association for reduced sense of smell in men and dream-enacting behavior in women. The number of NMS showed a strong dose-response relationship with PD, particularly in men. ORs were 5.5 (95% CI 3.4-8.8) for one, 17 (95% CI 10.4-28.0) for two, and 53.4 (95% CI 33.2-86.1) for three or more NMS in men; the corresponding ORs were 4.6 (95% CI 2.3-9.5), 6.7 (95% CI 2.9-15.6), and 23.6 (95% CI 10.7-52.4) in women (PNMS-interaction-with-sex = 0.07)., Conclusions: The number of NMS was associated with PD in a dose-response manner and the association appeared stronger in men than in women. These findings should be further investigated in population-based prospective studies.

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., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Growing evidence suggests that pesticide use may contribute to respiratory symptoms., Objective: We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers., Methods: Using the 2005-2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever ( n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever ( n = 3,939, 18%); men without wheeze were the referent., Results: In models evaluating current use of specific pesticides, 19 pesticides were significantly associated ( p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure-response models with up to five exposure categories, we saw evidence of an exposure-response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin., Conclusions: These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects.

Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

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.

Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1·5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index (BMI; HR = 1·22, 95% CI: 1·09-1·35 per 5 kg/m(2) ) and for higher cohort-entry BMI (HR 1·09, 95% CI: 1·03-1·16 per 5 kg/m(2) ) and waist circumference (HR = 1·06, 95% CI: 1·02-1·10 per 5 cm). Women who were the heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at greater risk compared to those with BMI 18·5 ≤ 25 at both time points (HR = 1·95, 95% CI: 1·33-2·86). Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood., (© 2014 John Wiley & Sons Ltd.)

Organophosphorous insecticides (OPs) are the most commonly used insecticides in US agriculture, but little information is available regarding specific OP use by individual farmers. We describe OP use for licensed private pesticide applicators from Iowa and North Carolina in the Agricultural Health Study (AHS) using lifetime pesticide use data from 701 randomly selected male participants collected at three time periods. Of 27 OPs studied, 20 were used by >1%. Overall, 95% had ever applied at least one OP. The median number of different OPs used was 4 (maximum=13). Malathion was the most commonly used OP (74%) followed by chlorpyrifos (54%). OP use declined over time. At the first interview (1993-1997), 68% of participants had applied OPs in the past year; by the last interview (2005-2007), only 42% had. Similarly, median annual application days of OPs declined from 13.5 to 6 days. Although OP use was common, the specific OPs used varied by state, time period, and individual. Much of the variability in OP use was associated with the choice of OP, rather than the frequency or duration of application. Information on farmers' OP use enhances our ability to characterize and understand the potential health effects of multiple OP exposures.

Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.

Purpose: The purpose of this study is to evaluate cancer risk associated with raising animals as commodities, which is associated with a variety of exposures, such as infectious agents and endotoxins., Methods: Information was available for 49,884 male farmers in the Agricultural Health Study, who reported livestock and poultry production at enrollment (1993-1997). Cancer incidence data were obtained through annual linkage to state registries. Using Poisson regression analyses, we evaluated whether the number and type of animals raised on the farm impacted cancer risk., Results: Overall, 31,848 (63.8%) male farmers reported raising any animals. Lung cancer risk decreased with increasing number of livestock on the farm (p trend = 0.04) and with raising poultry (Relative Risk (RR) = 0.6; 95% confidence interval (CI): 0.4-0.97). Raising poultry was associated with an increased risk of colon cancer (RR = 1.4; 95% CI: 0.99-2.0) with further increased with larger flocks (p trend = 0.02). Risk of non-Hodgkin lymphoma was also elevated in those who raised poultry (RR = 1.6; 95% CI: 1.0-2.4), but there was no evidence of increased risk with larger flocks (p trend = 0.5). Raising sheep was associated with a significantly increased risk of multiple myeloma (RR = 4.9; 95% CI: 2.4-12.0). Performing veterinary services increased the risk of Hodgkin lymphoma (RR = 12.2; 95% CI: 1.6-96.3)., Conclusions: We observed an inverse association between raising poultry and livestock and lung cancer risk and some evidence of increased risk of specific lymphohematopoietic malignancies with specific types of animals and performing veterinary services. Further research into associations between raising animals and cancer risk should focus on identification of etiologic agents.

Obesity is associated with increased risks of several cancers including colon and female breast. Pesticide use in agricultural populations has also been linked with higher risks of various cancers. However, the interaction between obesity and pesticide use on cancer risk has not been well studied. Using data from the Agricultural Health Study, we examined the association between body mass index (BMI) and the risk of cancer at 17 sites and the interaction between BMI and pesticide use. Pesticide applicators residing in Iowa and North Carolina and their spouses were enrolled between 1993 and 1997 and given a self-administered questionnaire to obtain pesticide use and other information. This analysis included 39,628 men and 28,319 women with height and weight data who were cancer-free at enrollment. Among these participants, 4,432 were diagnosed with cancer between enrollment and 2005 and 64% were overweight or obese. BMI (per 1 kg/m(2)) was positively associated with colon cancer in men (hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.02-1.09) and breast cancer in postmenopausal women (HR 1.03, 95% CI 1.01-1.06). In contrast, BMI was inversely associated with lung cancer in men, with a significant association in ever smokers (HR 0.92, 95% CI 0.88-0.97) and a null association in never smokers. The positive association between BMI and colon cancer in men was significant in those who ever used carbofuran (HR = 1.10, 95% CI 1.04-1.17; p-interaction = 0.04) or metolachlor (HR = 1.09, 95% CI 1.04-1.15; p-interaction = 0.02) but was null in non-users of these pesticides. Among male ever smokers, the inverse association between BMI and lung cancer was significant in non-users of carbofuran (HR = 0.87, 95% CI = 0.82-0.92) but was null in users of carbofuran (p-interaction = 0.02). These findings suggest that certain pesticides may modify the effects of BMI on the risks of colon and lung cancers.

Objective: To evaluate the relationship between pesticide use and myocardial infarction (MI) among farm women., Background: Little is known about the potential association between pesticide use and cardiovascular outcomes., Methods: We used logistic regression to evaluate pesticide use and self-reported incident nonfatal MI among women in the Agricultural Health Study., Results: Of those MI-free at enrollment (n = 22,425), 168 reported an MI after enrollment. We saw no association with pesticide use overall. Six of 27 individual pesticides evaluated were significantly associated with nonfatal MI, including chlorpyrifos, coumaphos, carbofuran, metalaxyl, pendimethalin, and trifluralin, which all had odds ratios >1.7. These chemicals were used by <10% of the cases, and their use was correlated, making it difficult to attribute the risk elevation to a specific pesticide., Conclusion: Pesticides may contribute to MI risk among farm women.

Studies examining the association between maternal pesticide exposure and low birth weight yield conflicting results. The authors examined the association between maternal pesticide use and birth weight among women in the Agricultural Health Study, a large study of pesticide applicators and their spouses in Iowa and North Carolina. The authors evaluated self-reported pesticide use of 27 individual pesticides in relation to birth weight among 2246 farm women whose most recent singleton birth occurred within 5 years of enrollment (1993-1997). The authors used linear regression models adjusted for site, preterm birth, medical parity, maternal body mass index, height, and smoking. The results showed that mean infant birth weight was 3586 g (+/- 546 g), and 3% of the infants were low birth weight (<2500 g). First-trimester pesticide-related tasks were not associated with birth weight. Ever use of the pesticide carbaryl was associated with decreased birth weight (-82 g, 95% confidence interval [CI] = -132, -31). This study thus provides limited evidence about pesticide use as a modulator of birth weight. Overall, the authors observed no associations between birth weight and pesticide-related activities during early pregnancy; however, the authors have no data on temporal specificity of individual pesticide exposures prior to or during pregnancy and therefore cannot draw conclusions related to these exposure windows. Given the widespread exposure to pesticide products, additional evaluation of maternal pregnancy exposures at specific time windows and subsequent birth outcomes is warranted.

Paraquat (1,1'-dimethyl-4, 4'-bipyridinium dichloride) is a nonselective herbicide that is extremely toxic after acute exposure. It was once widely used in North America and is still used in some countries, including the United States. Although there is little firm evidence that paraquat is a carcinogen, previous studies have suggested a potential relationship with some cancers. This prospective cohort study was performed to evaluate the association between lifetime paraquat exposure and cancer incidence among licensed pesticide applicators with 9.1 years of median follow-up. The lifetime ever-use of paraquat was evaluated in 56,224 subjects at baseline and exposure-response relationship was evaluated in 24,667 subjects (44%) who provided detailed information on total life-time paraquat exposure in a second questionnaire. Among the total subjects, the risk for non-Hodgkin's lymphoma (NHL) in the exposed group was marginally elevated (Relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) compared to the non-exposed group. However, among the 24,667 applicators who supplied total life-time exposure days, the highest tertile of lifetime exposure-days (LE) and intensity-weighted lifetime exposure-days (IWLE) was not significantly associated with NHL risk (RR, 1.57; 95%CI, 0.57-4.23 for LE; RR, 1.42; 95%CI, 0.40-4.71 for IWLE, respectively) and there was no significant exposure-response trend (p-trend > 0.1). There was some suggestion of a possible link between paraquat exposure and NHL risk in humans, but the inconsistency in exposure level trend suggests that this could be a chance finding.

Background: Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease., Methods/design: We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing., Discussion: EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.