A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides

Background: Organochlorine insecticides (OCs) have historically been used worldwide to control insects, although most have now been banned in developed countries. Evidence for an association between OC exposures and cancer predominantly comes from occupational and population based-studies among men. We evaluated the association between the use of specific OCs and cancer among the female spouses of pesticide applicators in the Agricultural Health Study. Methods: At enrollment (1993–1997), spouses of private applicators in the cohort provided information about their own use of pesticides, including seven OCs (aldrin, chlordane, dieldrin, DDT, heptachlor, lindane, and toxaphene), and information on potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for cancers (n ≥ 3 exposed cases) reported to state cancer registries from enrollment through 2012 (North Carolina) and 2013 (Iowa), and use of the individual OCs, as well as use of any of the specific OCs. Results: Among 28,909 female spouses, 2191 (7.58%) reported ever use of at least one OC, of whom 287 were diagnosed with cancer. Most cancers were not associated with OC use. Risk of glioma was increased among users of at least one OC (Nexposed = 11, RR = 3.52, 95% CI 1.72–7.21) and specifically among lindane users (Nexposed = 3, RR = 4.45, 95% CI 1.36–14.55). Multiple myeloma was associated with chlordane (Nexposed = 6, RR = 2.71, 95% CI 1.12–6.55). Based on 3 exposed cases each, there were also positive associations between pancreatic cancer and lindane, and ER-PR- breast cancer and dieldrin. No other associations with breast cancer were found. Conclusions: Overall, there were some associations with OC use and cancer incidence, however we were limited by the small number of exposed cancer cases. Future research should attempt to expand on these findings by assessing environmental sources of OC exposures, to fully evaluate the role of OC exposures on cancer risk in women

Estimating Water Supply Arsenic Levels in the New England Bladder Cancer Study

Background: Ingestion of inorganic arsenic in drinking water is recognized as a cause of bladder cancer when levels are relatively high (≥ 150 µg/L). The epidemiologic evidence is less clear at the low-to-moderate concentrations typically observed in the United States. Accurate retrospective exposure assessment over a long time period is a major challenge in conducting epidemiologic studies of environmental factors and diseases with long latency, such as cancer. Objective: We estimated arsenic concentrations in the water supplies of 2,611 participants in a population-based case–control study in northern New England. Methods: Estimates covered the lifetimes of most study participants and were based on a combination of arsenic measurements at the homes of the participants and statistical modeling of arsenic concentrations in the water supply of both past and current homes. We assigned a residential water supply arsenic concentration for 165,138 (95%) of the total 173,361 lifetime exposure years (EYs) and a workplace water supply arsenic level for 85,195 EYs (86% of reported occupational years). Results: Three methods accounted for 93% of the residential estimates of arsenic concentration: direct measurement of water samples (27%; median, 0.3 µg/L; range, 0.1–11.5), statistical models of water utility measurement data (49%; median, 0.4 µg/L; range, 0.3–3.3), and statistical models of arsenic concentrations in wells using aquifers in New England (17%; median, 1.6 µg/L; range, 0.6–22.4). Conclusions: We used a different validation procedure for each of the three methods, and found our estimated levels to be comparable with available measured concentrations. This methodology allowed us to calculate potential drinking water exposure over long periods

Agricultural Exposures and Stroke Mortality in the Agricultural Health Study

Exposures associated with common agricultural activities may increase risk of stroke. The authors evaluated associations between self-reported agricultural activities including pesticide use and handling of crops and stroke mortality among 51,603 male pesticide applicators enrolled in the Agricultural Health Study (AHS). Vital status was obtained through 2008. Stroke mortality was defined by underlying or contributing cause of death (ICD-9 430–438, ICD-10 I60-I69). Information regarding lifetime pesticide use, working with crops or animals, engagement in other agricultural activities, and potential confounders was self-reported at enrollment. Cox proportional hazards models, with age as the time scale, were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for state of residence, smoking status, and alcohol consumption. Median follow-up time was 13 years, during which 308 stroke deaths occurred. No measure of overall or specific pesticide use was positively associated with mortality due to stroke. Stroke mortality was inversely associated with handling hay, grain, or silage at least once each year as reported at enrollment (HR: 0.75; 95% CI: 0.58, 0.98). There was no evidence of an association between pesticide use and stroke mortality. The inverse association between handling of hays and grains and stroke mortality may be due to (1) those engaging in such activities being healthier than those who did not or (2) exposure to some biological agent present in hays and grains. Further investigation of incident stroke, rather than stroke mortality, as well as stroke subtypes are needed to determine the full role of agricultural exposures and stroke

Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007).

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

Early-Life Farm Exposures and Eczema Among Adults in the Agricultural Lung Health Study

Background Several studies conducted in Europe have suggested a protective association between early-life farming exposure and childhood eczema or atopic dermatitis; however, few studies have examined associations in adults. Objectives We investigated associations between early-life exposures and eczema among 3217 adult farmers and farm spouses (mean age, 62.8 years) in a case–control study nested within an US agricultural cohort. Methods We used sampling-weighted logistic regression to estimate odds ratios and 95% confidence intervals for associations between early-life exposures and self-reported doctor-diagnosed eczema (273 cases) and polytomous logistic regression to estimate odds ratios (95% confidence intervals) for a 4-level outcome combining information on eczema and atopy (specific IgE ≥ 0.35). Additionally, we explored genetic and gene–environment associations with eczema. Results Although early-life farming exposures were not associated with eczema overall, several early-life exposures were associated with a reduced risk of having both eczema and atopy. Notably, results suggest stronger protective associations among individuals with both eczema and atopy than among those with either alone. For example, odds ratios (95% confidence intervals) for having a mother who did farm work while pregnant were 1.01 (0.60, 1.69) for eczema alone and 0.80 (0.65, 0.99) for atopy alone, but 0.54 (0.33, 0.80) for having both. A genetic risk score based on previously identified atopic dermatitis variants was strongly positively associated with eczema, and interaction testing suggested protective effects of several early-life farming exposures only in individuals at lower genetic risk. Conclusions In utero and childhood farming exposures are associated with decreased odds of having eczema with atopy in adults

Lifetime Pesticide Use and Telomere Shortening among Male Pesticide Applicators in the Agricultural Health Study

Background: Telomere length (TL) in surrogate tissues may be influenced by environmental exposures. Objective: We aimed to determine whether lifetime pesticides use is associated with buccal cell TL. Methods: We examined buccal cell TL in relation to lifetime use of 48 pesticides for 1,234 cancer-free white male pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of 57,310 licensed pesticide applicators. Participants provided detailed information on lifetime use of 50 pesticides at enrollment (1993–1997). Buccal cells were collected from 1999 to 2006. Relative telomere length (RTL) was measured using quantitative real-time polymerase chain reaction. We used linear regression modeling to evaluate the associations between specific pesticides and the logarithm of RTL, adjusting for age at buccal cell collection, state of residence, applicator license type, chewing tobacco use, and total lifetime days of all pesticide use. Results: The mean RTL for participants decreased significantly in association with increased lifetime days of pesticide use for alachlor (p = 0.002), 2,4-dichlorophenoxyacetic acid (2,4-D; p = 0.004), metolachlor (p = 0.01), trifluralin (p = 0.05), permethrin (for animal application) (p = 0.02), and toxaphene (p = 0.04). A similar pattern of RTL shortening was observed with the metric lifetime intensity-weighted days of pesticide use. For dichlorodiphenyltrichloroethane (DDT), we observed significant RTL shortening for lifetime intensity-weighted days (p = 0.04), but not for lifetime days of DDT use (p = 0.08). No significant RTL lengthening was observed for any pesticide. Conclusion: Seven pesticides previously associated with cancer risk in the epidemiologic literature were inversely associated with RTL in buccal cell DNA among cancer-free pesticide applicators. Replication of these findings is needed because we cannot rule out chance or fully rule out bias

Herbicide, fumigant, and fungicide use and breast cancer risk among farmers' wives

Background: 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

Interaction between Genetic Risk Scores for Reduced Pulmonary Function and Smoking, Asthma and Endotoxin

Rationale Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene–environment interactions, but studies are few. Methods We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case–control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV1, FVC and FEV1/FVC. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top (p value\u3c5×10−9) genetic variants, after clumping based on distance (±250 kb) and linkage disequilibrium (r2=0.5). We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions. Results Each trait was highly significantly associated with its GRS (all three p values\u3c8.9×10−8). The inverse association of the GRS with FEV1/FVC was stronger for current smokers (pinteraction=0.017) or former smokers (pinteraction=0.064) when compared with never smokers and among asthmatics compared with non-asthmatics (pinteraction=0.053). No significant interactions were observed between any GRS and house dust endotoxin. Conclusions Evaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma

Formaldehyde and leukemia: Epidemiology, potential mechanisms, and implications for risk assessment

Formaldehyde is widely used in the United States and other countries. Occupational and environmental exposures to formaldehyde may be associated with an increased risk of leukemia in exposed individuals. However, risk assessment of formaldehyde and leukemia has been challenging due to inconsistencies in human and animal studies and the lack of a known mechanism for leukemia induction. Here we provide a summary of the symposium at the Environmental Mutagen Society Meeting in 2008, which focused on the epidemiology of formaldehyde and leukemia, potential mechanisms, and implication for risk assessment, with emphasis on future directions in multidisciplinary formaldehyde research

Insecticide use and breast cancer risk among farmers’ wives in the agricultural health study

BACKGROUND: Some epidemiologic and laboratory studies suggest that insecticides are related to increased breast cancer risk, but the evidence is inconsistent. Women engaged in agricultural work or who reside in agricultural areas may experience appreciable exposures to a wide range of insecticides. OBJECTIVE: We examined associations between insecticide use and breast cancer incidence among wives of pesticide applicators (farmers) in the prospective Agricultural Health Study. METHODS: Farmers and their wives provided information on insecticide use, demographics, and reproductive history at enrollment in 1993–1997 and in 5-y follow-up interviews. Cancer incidence was determined via cancer registries. Among 30,594 wives with no history of breast cancer before enrollment, we examined breast cancer risk in relation to the women’s and their husbands’ insecticide use using Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average 14.7-y follow-up, 39% of the women reported ever using insecticides, and 1,081 were diagnosed with breast cancer. Although ever use of insecticides overall was not associated with breast cancer risk, risk was elevated among women who had ever used the organophosphates chlorpyrifos [HR = 1:4 (95% CI: 1.0, 2.0)] or terbufos [HR = 1:5 (95% CI: 1.0, 2.1)], with nonsignificantly increased risks for coumaphos [HR = 1:5 (95% CI: 0.9, 2.5)] and heptachlor [HR = 1:5 (95% CI: 0.7, 2.9)]. Risk in relation to the wives’ use was associated primarily with premenopausal breast cancer. We found little evidence of differential risk by tumor estrogen receptor status. Among women who did not apply pesticides, the husband’s use of fonofos was associated with elevated risk, although no exposure–response trend was observed. CONCLUSION: Use of several organophosphate insecticides was associated with elevated breast cancer risk. However, associations for the women’s and husbands’ use of these insecticides showed limited concordance. Ongoing cohort follow-up may help clarify the relationship, if any, between individual insecticide exposures and breast cancer risk