Although limited, epidemiologic studies suggest possible associations between butylate use and cancer risk, specifically prostate cancer and non-Hodgkin lymphoma (NHL). We examined butylate use and cancer risk more broadly in the AHS, a cohort of licensed pesticide applicators in Iowa and North Carolina. Pesticide use information was collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios(RR) and 95% confidence intervals(CI). Two exposure metrics were used: lifetime exposure days(LD) and intensity-weighted lifetime exposure days(IWLD). We used two referent groups: unexposed to butylate and the lowest butylate usage category. This analysis included 19,655 applicators with complete butylate use information; 5,297 applicators were exposed to butylate, making this the largest study of butylate to-date. The mean follow-up time since enrollment was 9 years. Prostate cancer risk was significantly elevated among applicators in the highest LD category in both referent groups (low exposed referent: RRLD=2.09,95%CI=1.27–3.44). We observed a significantly elevated joint effect of prostate cancer family history and high butylate usage across both exposure metrics and both referent groups (low exposed referent: RRLD=2.00, 95%CI=1.07–3.74), and a non-significant, elevated interaction between butylate use and prostate cancer family history, similar to a previous AHS finding. Statistically significant increased risks and exposure-response trends were seen for all lymphohematopoietic cancers (AL) and NHL for both exposure metrics and referent groups (low exposed referent: AL:RRLD =2.27, 95%CI = 1.18–4.37; NHL: RRLD=3.44, 95%CI =1.29– 9.21). Our analysis did not find meaningful associations for other cancers analyzed. Further study is warranted for AL, NHL and prostate cancers.
butylate; pesticide; cancer; agricultural health study
To assess whether pesticide use practices were associated with injury mortality among 51,035 male farmers from North Carolina and Iowa enrolled in the Agricultural Health Study.
We used Cox proportional hazards models adjusted for age and state to estimate fatal injury risk associated with self-reported use of 49 specific pesticides, personal protective equipment, specific types of farm machinery, and other farm factors collected 1–15 years preceding death. Cause-specific mortality was obtained through linkage to mortality registries.
We observed 338 injury fatalities over 727,543 person-years of follow-up (1993–2008). Fatal injuries increased with days per year of pesticide application, with the highest risk among those with 60+ days of pesticide application annually (Hazard Ratio (HR) =1.87; 95% Confidence Interval (CI) = 1.10, 3.18). Chemical-resistant glove use was associated with decreased risk (HR=0.73; 95%CI=0.58, 0.93), but adjusting for glove use did not substantially change estimates for individual pesticides or pesticide use overall. Herbicides were associated with fatal injury, even after adjusting for operating farm equipment, which was independently associated with fatal injury. Ever use of five of 18 herbicides (2,4,5–T, paraquat, alachlor, metribuzin, and butylate) were associated with elevated risk. In addition, 2,4–D and cyanazine were associated with fatal injury in exposure-response analyses. There was no evidence of confounding of these results by other herbicides.
The association between application of pesticides, particularly certain herbicides, and fatal injuries among farmers should be interpreted cautiously but deserves further evaluation, with particular focus on understanding timing of pesticide use and fatal injury.
pesticides; mortality; wounds; injuries
Lung cancer patients with mutations in EGFR tyrosine kinase have improved prognosis when treated with EGFR inhibitors. We hypothesized that EGFR mutations may be related to residential radon or passive tobacco smoke.
This hypothesis was investigated by analyzing EGFR mutations in seventy lung tumors from a population of never and long-term former female smokers from Missouri with detailed exposure assessments. The relationship with passive-smoking was also examined in never-smoking female lung cancer cases from the Mayo clinic.
Overall, the frequency of EGFR mutation was 41% [95% Confidence Interval (CI): 32-49%]. Neither radon nor passive-smoking exposure was consistently associated with EGFR mutations in lung tumors.
The results suggest that EGFR mutations are common in female, never-smoking, lung cancer cases from the U.S, and EGFR mutations are unlikely due to exposure to radon or passive-smoking.
EGFR mutations; never-smokers; lung cancer; radon; passive-smoking; second hand smoke; tobacco smoke
Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects.
We used Poisson regression to calculate rate ratios (RR) and 95% confidence intervals (CI) for associations between methyl bromide use and all cancers combined and 12 specific sites among 53,588 Agricultural Health Study (AHS) pesticide applicators with follow-up from 1993–2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score.
A total of 7,814 applicators (14.6%) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR=1.42; 95% CI: 0.51–3.95 and RR=3.13; 95% CI: 1.25–7.80 for low and high use compared with no use; ptrend=0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a non-significant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance.
Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.
methyl bromide; fumigant; pesticide; cancer
We investigated the relationship between agricultural pesticides and colorectal cancer incidence in the Agricultural Health Study. A total of 56,813 pesticide applicators with no prior history of colorectal cancer were included in this analysis. Detailed pesticide exposure and other information were obtained from self-administered questionnaires completed at the time of enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2002. A total of 305 incident colorectal cancers (212 colon, 93 rectum) were diagnosed during the study period, 1993-2002. Although most of the 50 pesticides studied were not associated with colorectal cancer risk, chlorpyrifos use showed significant exposure response trend (p for trend = 0.008) for rectal cancer, rising to a 2.7-fold (95% confidence interval: 1.2-6.4) increased risk in the highest exposure category. Aldicarb was associated with a significantly increased risk of colon cancer (p for trend = 0.001), based on a small number of exposed cases, with the highest exposure category resulting in a 4.1-fold increased risk (95% confidence interval: 1.3-12.8). In contrast dichlorophenoxyacetic acid showed a significant inverse association with colon cancer but the association was not monotonic. Our findings should be interpreted cautiously since the literature suggesting that pesticides are related to colorectal cancer is limited. Nonetheless the possibility of an association between exposure to certain pesticides and incidence of colorectal cancer among pesticide applicators deserves further evaluation.
agriculture; colorectal cancer; farmers; insecticides; occupational exposure; pesticides
Although impaired lung function in general has been associated with an increased risk of lung cancer, past studies typically have not attempted to investigate separately the obstructive and restrictive components of respiratory impairment. To deal with this question further, data from a large (n = 176 997) cohort of male Swedish construction workers, for whom spirometry measurements before follow‐up were available, were analysed.
Cancer incidence for 1971–2001 was obtained through linkage with the national cancer registry. Using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD), subjects were classified into five categories of lung function: normal, mild COPD, moderate COPD, severe COPD and restrictive lung disease (RLD). Rate ratios (RR) and 95% confidence intervals (CI) for lung cancer across lung function categories were calculated using Poisson regression, adjusted for age and smoking. Other end points (histological types of lung cancer, non‐lung tobacco‐related cancers, other cancers, total mortality) were also investigated.
834 incident cases of lung cancer were identified. Increased rates of lung cancer were observed for both COPD (mild: RR 1.5, 95% CI 1.2 to 1.9; moderate/severe: RR 2.2, 95% CI 1.8 to 2.7) and RLD (RR 2.0, 95% CI 1.6 to 2.5) relative to normal lung function. These associations did not meaningfully change on applying follow‐up lag times of 5, 10 and 15 years after spirometry. When analysed by histological type, associations with both COPD and RLD were stronger for squamous cell carcinoma and small cell carcinoma, and weaker for adenocarcinoma. Both COPD and RLD were associated with increased rates of total mortality.
Obstructive and restrictive impairments in lung function are associated with increased lung cancer risk.
The Agricultural Health Study (AHS) is a prospective study of licensed pesticide applicators (largely farmers) and their spouses in Iowa and North Carolina. We evaluate the impact of occupational pesticide exposure misclassification on relative risks using data from the cohort and the AHS Pesticide Exposure Study (AHS/PES).
We assessed the impact of exposure misclassification on relative risks using the range of correlation coefficients observed between measured post-application urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) and chlorpyrifos metabolite and exposure estimates based on an algorithm from 83 AHS pesticide applications.
The correlations between urinary levels of 2,4-D and chlorpyrifos metabolite and estimated exposure intensity scores from the expert-derived algorithm were about 0.4 for 2,4-D (n=64), 0.8 for liquid chlorpyrifos (n=4), and 0.6 for granular chlorpyrifos (n=12). Correlations of urinary levels with individual exposure determinants (e.g., kilograms of active ingredient used, duration of application, or number of acres treated) were lower and ranged from −0.36 to 0.19. These findings indicate that scores from an a priori expert-derived algorithm developed for the AHS were more closely related to measured urinary levels than the several individual exposure determinants evaluated here. Estimates of potential bias in relative risks observed in the AHS based on the correlations from the AHS/PES and the proportion of the AHS cohort exposed to various pesticides indicate that nondifferential misclassification of exposure using the algorithm would bias some estimates toward the null, but less than the misclassification associated with individual exposure determinants.
Based on these correlations and the proportion of the AHS cohort exposed to various pesticides, the potential bias in relative risks from nondifferential exposure misclassification is reduced when exposure estimates are based on an expert algorithm compared to estimates based on separate individual exposure determinants often used in epidemiologic studies. Although correlations between algorithm scores and urinary levels were quite good (i.e., correlations between 0.4 and 0.8), exposure misclassification would still bias relative risk estimates in the AHS towards the null and diminish study power.
Previous research demonstrates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, human biomonitoring studies indicate increased genetic damage (e.g. chromosomal aberrations) with pesticide exposure. Given that the nucleotide excision repair (NER) pathway repairs a broad range of DNA damage, we evaluated interactions between pesticide exposure and 324 single-nucleotide polymorphisms (SNPs) tagging 27 NER genes among 776 prostate cancer cases and 1444 male controls in a nested case–control study of white Agricultural Health Study pesticide applicators. We determined interaction P values using likelihood ratio tests from logistic regression models and three-level pesticide variables (none/low/high) based on lifetime days of use weighted to an intensity score. We adjusted for multiple comparisons using the false discovery rate (FDR) method. Of the 17 interactions that met FDR <0.2, 3 displayed a monotonic increase in prostate cancer risk with increasing exposure in one genotype group and no significant association in the other group. Men carrying the variant A allele at ERCC1 rs2298881 exhibited increased prostate cancer risk with high versus no fonofos use [odds ratio (OR) 2.98; 95% confidence interval (CI) 1.65–5.39; Pinteract = 3.6 × 10−4; FDR-adjusted P = 0.11]. Men carrying the homozygous wild-type TT genotype at two correlated CDK7 SNPs, rs11744596 and rs2932778 (r2 = 1.0), exhibited increased risk with high versus no carbofuran use (OR 2.01; 95% CI 1.31–3.10 for rs11744596; Pinteract = 7.2 × 10−4; FDR-adjusted P = 0.09). In contrast, we did not observe associations among men with other genotypes at these loci. While requiring replication, our findings suggest a role for NER genetic variation in pesticide-associated prostate cancer risk.
To explore associations with prostate cancer and farming, it is important to investigate the relationship between pesticide use and single nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes.
We evaluated pesticide-SNP interactions between 45 pesticides and 1,913 XME SNPs with respect to prostate cancer among 776 cases and 1,444 controls in the Agricultural Health Study.
We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test.
A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate-cysteine ligase (GCLC) (p-interaction=1.0×10−4); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI: 1.9–7.3). Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hyrdolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, increased prostate cancer risk was observed with high compared to no petroleum oil/petroleum distillate (OR=1.9, 95% CI: 1.1–3.2, p-interaction=0.01), (OR=2.1, 95% CI: 1.1–4.0, p-interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5–6.0 p-interaction=2.0×10−3) use, respectively. No interactions were deemed noteworthy at the false discovery rate = 0.20 level; the number of observed interactions in XMEs was comparable to the number expected by chance alone.
We observed several pesticide-SNP interactions in oxidative stress and phase I/phase II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk.
Prostate cancer; pesticides; xenobiotic metabolizing enzymes; single nucleotide polymorphism; interaction
Pesticide exposures can be reduced by use of personal protective equipment as well as proper mixing and application practices. We examined the effects of risk-accepting personality on personal protective equipment (PPE) use and mixing and application practices among private pesticide applicators and their spouses within the Agricultural Health Study (AHS) in Iowa and North Carolina and commercial applicators in Iowa. The AHS follow-up questionnaire included four questions designed to assess attitudes toward risk. Analysis was limited to those who were currently working on a farm or registered as a commercial applicator and indicated current pesticide use (n=25,166). Respondents who answered three or more questions in the affirmative (private applicators: n=4,160 (21%); commercial applicators: n=199 (14%); spouses: n=829 (23%)) were classified as having a risk-accepting personality. Logistic regression was used to evaluate specific work practices associated with risk-accepting attitudes. Among private applicators, the likelihood of using any PPE when mixing or loading pesticides was lower among risk-acceptors compared to risk-averse individuals (odds ratio (OR) = 0.72; 95% Confidence Interval (CI): 0.65 – 0.79). A similar relationship was observed among commercial applicators (OR = 0.77, 95% CI: 0.34 – 1.77) but not among spouses (OR = 1.09, 95% CI: 0.90 – 1.33). Among private applicators, risk-acceptors were more likely than the risk-averse to apply pesticides within 50 ft of the home (OR=1.21; 95% CI: 1.01 – 1.44), compared to further than ¼ mile. Our findings suggest that the decisions to use personal protective equipment and properly handle/apply pesticides may be driven by risk-accepting personality traits.
personal protective equipment; risk-accepting behavior; Agricultural Health Study; pesticide
Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.
The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants. Missing pesticide use information from participants who did not complete the second questionnaire impedes both long-term pesticide exposure estimation and statistical inference of risk for health outcomes. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides for 20,968 applicators who did not complete the second questionnaire. To assess the imputation procedure, a 20% random sample of participants was withheld for comparison. The observed and imputed prevalence of any pesticide use in the holdout dataset were 85.7% and 85.3%, respectively. The distribution of prevalence and days/year of use for specific pesticides were similar across observed and imputed in the holdout sample. When appropriately implemented, multiple imputation can reduce bias and increase precision and can be more valid than other missing data approaches.
agriculture; cohort studies; missing data; pesticides; precision
Objectives: To identify and quantify determinants of captan exposure among 74 private orchard pesticide applicators in the Agricultural Health Study (AHS). To adjust an algorithm used for estimating pesticide exposure intensity in the AHS based on these determinants and to compare the correlation of the adjusted and unadjusted algorithms with urinary captan metabolite levels.
Methods: External exposure metrics included personal air, hand rinse, and dermal patch samples collected from each applicator on 2 days in 2002–2003. A 24-h urine sample was also collected. Exposure determinants were identified for each external metric using multiple linear regression models via the NLMIXED procedure in SAS. The AHS algorithm was adjusted, consistent with the identified determinants. Mixed-effect models were used to evaluate the correlation between the adjusted and unadjusted algorithm and urinary captan metabolite levels.
Results: Consistent determinants of captan exposure were a measure of application size (kilogram of captan sprayed or application method), wearing chemical-resistant (CR) gloves and/or a coverall/suit, repairing spray equipment, and product formulation. Application by airblast was associated with a 4- to 5-fold increase in exposure as compared to hand spray. Exposure reduction to the hands, right thigh, and left forearm from wearing CR gloves averaged ∼80%, to the right and left thighs and right forearm from wearing a coverall/suit by ∼70%. Applicators using wettable powder formulations had significantly higher air, thigh, and forearm exposures than those using liquid formulations. Application method weights in the AHS algorithm were adjusted to nine for airblast and two for hand spray; protective equipment reduction factors were adjusted to 0.2 (CR gloves), 0.3 (coverall/suit), and 0.1 (both).
Conclusions: Adjustment of application method, CR glove, and coverall weights in the AHS algorithm based on our exposure determinant findings substantially improved the correlation between the AHS algorithm and urinary metabolite levels.
agriculture; captan; dermal exposure—pesticides, determinants of exposure; exposure assessment—mixed models; orchards; pesticide exposure; variance components
Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993–1997) through 2007 to state-specific rates. To compensate for the cohort's overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMRapplicators = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMRspouses = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes.
agriculture; healthy worker effect; mortality; neoplasms; pesticides; wounds and injuries
Background: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage.
Objectives: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case–control study of white Agricultural Health Study (AHS) pesticide applicators.
Methods: We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach.
Results: The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (pinteract) = 9.3 × 10–6; FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2.
Conclusions: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.
DNA repair; gene–environment interactions; pesticide; polymorphisms; prostate cancer
An algorithm developed to estimate pesticide exposure intensity for use in epidemiologic analyses was revised based on data from two exposure monitoring studies. In the first study, we estimated relative exposure intensity based on the results of measurements taken during the application of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n = 17). Modifications to the algorithm weighting factors were based on geometric means (GM) of post-application urine concentrations for applicators grouped by application method and use of chemically-resistant (CR) gloves. Measurement data from a second study were also used to evaluate relative exposure levels associated with airblast as compared to hand spray application methods. Algorithm modifications included an increase in the exposure reduction factor for use of CR gloves from 40% to 60%, an increase in the application method weight for boom spray relative to in-furrow and for air blast relative to hand spray, and a decrease in the weight for mixing relative to the new weights assigned for application methods. The weighting factors for the revised algorithm now incorporate exposure measurements taken on Agricultural Health Study (AHS) participants for the application methods and personal protective equipment (PPE) commonly reported by study participants.
pesticides; exposure algorithm; epidemiology; 2,4-D; chlorpyrifos; captan
Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction between pesticide use, 8q24 variants and prostate cancer risk. The authors estimated odds ratios (ORs) and 95% confidence intervals (CIs) for interactions between 211 8q24 variants, 49 pesticides and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (p<0.05) with exposure to the organophosphate insecticide, fonofos, after correction for multiple testing, per allele ORnonexposed= 1.17 (95% CI: 0.93, 1.48), per allele ORlow=1.30 (95% CI: 0.75, 2.27), per allele ORhigh=4.46 (95% CI: 2.17, 9.17), p-interaction=0.002, adjusted p-interaction = 0.02. Similar effect modification was observed for three other organophosphate insecticides, coumaphos, terbufos, and phorate and one pyrethroid insecticide, permethrin. Among ever users of fonofos, subjects with 3 or 4 risk alleles at rs7837328 and rs4242382 had approximately 3 times the risk of prostate cancer (OR=3.14 95% CI: 1.41, 7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction between variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biologic mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.
Prostate cancer; pesticides; 8q24; single nucleotide polymorphism; interaction
Our objective is to re-evaluate cancer incidence among Agricultural Health Study participants.
Standardized incidence ratios (SIR) and Relative Standardized Ratios were calculated.
A significant excess of prostate cancer was seen for private and commercial applicators, SIR = 1.19 (95% Confidence Interval (CI) 1.14, 1.25) and SIR = 1.28 (95% CI 1.00, 1.61), respectively. Excesses were observed for lip cancer, SIR = 1.97 (95% CI 1.02, 3.44), and multiple myeloma, SIR = 1.42 (95% CI 1.00, 1.95) among private applicators from North Carolina and for marginal zone lymphoma among Iowa spouses, SIR = 2.34 (95% CI 1.21, 4.09).
While lower rates of smoking and increased physical activity probably contribute to the lower overall cancer incidence, agricultural exposures including pesticides, viruses, bacteria, sunlight, and other chemicals may increase risks for specific cancer sites.
Background: An association may exist between pesticide exposure and suicide.
Objective: We sought to evaluate the existence of an association between pesticide use and suicide using data from the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina.
Methods: Via linkage to state mortality files and the National Death Index, we identified 110 suicides occurring between enrollment in the AHS (from 1993 to 1997) and 31 May 2009, among 81,998 cohort members contributing 1,092,943 person-years of follow-up. The average length of follow-up was 13.3 years. AHS participants provided data on pesticide use and potential confounders via self-administered questionnaires at enrollment. We evaluated several measures of pesticide use: use of any pesticide, ever use of 50 specific pesticides, cumulative lifetime days of use and intensity-adjusted cumulative lifetime days of use of 22 specific pesticides, and ever use of 10 functional and chemical classes of pesticides. We used Cox proportional hazards regression models to estimate adjusted hazard ratios and 95% confidence intervals.
Results: After adjusting for age at enrollment, sex, number of children in family, frequency of alcohol consumption during the past 12 months, and smoking status, we found no association between prior pesticide use and suicide in applicators and their spouses. Results were the same for applicators and spouses together or for applicators alone and were consistent across several measures of pesticide use.
Conclusions: Our findings do not support an association between moderate pesticide use and suicide.
farmers; pesticide applicators; pesticides; spouses; suicide
Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association.
Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure.
Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic.
Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.
agriculture; atrazine; cancer; cohort study; epidemiology; pesticide
AGRICOH is a recently formed consortium of agricultural cohort studies involving 22 cohorts from nine countries in five continents: South Africa (1), Canada (3), Costa Rica (2), USA (6), Republic of Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). The aim of AGRICOH, initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC), is to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e.g., use of infrequently applied chemicals) or relatively rare outcomes (e.g., certain types of cancer, neurologic and auto-immune diseases). To facilitate future projects the need for data harmonization of selected variables is required and is underway. Altogether, AGRICOH provides excellent opportunities for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides.
agriculture; cohort studies; consortium, pesticides; occupational exposures
The aim was to develop quantitative estimates of farmers’ pesticide exposure to atrazine and to provide an overview of background levels of selected non-persistent pesticides among corn farmers in a longitudinal molecular epidemiologic study.
The study population consisted of 30 Agricultural Health Study farmers from Iowa and 10 nonfarming controls. Farmers completed daily and weekly diaries from March to November in 2002 and 2003 on pesticide use and other exposure determinants. Urine samples were collected at 10 timepoints relative to atrazine application and other farming activities. Pesticide exposure was assessed using urinary metabolites and diaries.
The analytical limit of detection (LOD) ranged between 0.1–0.2 μg/l for all pesticide analytes except for isazaphos (1.5 μg/l) and diazinon (0.7 μg/l). Farmers had higher geometric mean urinary atrazine mercapturate (AZM) values than controls during planting (1.1 vs.
Urinary AZM levels in farmers were largely driven by recent application of atrazine. Therefore, the amount of atrazine applied is likely to provide valid surrogates of atrazine exposure in epidemiologic studies. Elevated background levels of non-persistent pesticides, especially 2,4-D, indicate importance in epidemiologic studies of capturing pesticide exposures that might not be directly related to the actual application.
exposure assessment; pesticide exposure; urine; farmers; prospective studies
In the Agricultural Health Study, information on participant live births was largely provided by female partners of male private applicators. At the Iowa site, such information was available for 13,599 (42.9%) of 31,707 applicators. To improve identification of live births among Iowa participants, we used a probabilistic and deterministic approach to link available demographic data from 31,707 households and information on live births from 13,599 households with 1,014,916 Iowa birth certificates. Record linkage identified 16,611 (93.7%) of 17,719 reported live births and 17,883 additional live births, most (14,411 or 80.6%) not identified due to non-participation by female partners. This record linkage produced an expanded cohort of live born children among Iowa participants, which will facilitate improved study of the effects of agricultural exposures, including pesticides, on selected birth outcomes and childhood disease.
children; occupational exposures; pesticides; pregnancy; prospective cohort
Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina.
Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure.
Of the 47,625 pesticide applicators included in this analysis, 3,657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers – the only cancers for which we had sufficient numbers to explore associations.
We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer.
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