Reliability of baseline self-reported information in the AGRICAN cohort.

PURPOSE: An important challenge in epidemiology is to ensure the reliability of collected data. Very few studies have been conducted in farming populations. We assessed the reliability of self-reported data on lifestyle, reproductive history, health and agricultural activities and tasks from the AGRICAN cohort. METHODS: Our analysis focused on 739 individuals from the 181,842 cohort members who completed the questionnaire twice between 2005 and 2007 with a median time interval of 452 days. Consistency in the responses to questionnaire items (lifestyle, health and agricultural activities including pesticide treatments) was assessed by the percentage of exact agreement (PA), Cohen's Kappa value (K) and the intraclass correlation coefficient (ICC). RESULTS: Agreement was substantial to almost perfect for education, smoking, reproductive history and most health indicators (K/ICC > 0.61). Agreement was moderate for alcohol consumption and fair for diet. Agreement was substantial for animal and crop farming activities and tasks such as pesticide use on crops and protective equipment use (PA 81-99%, K/ICC 0.61-0.96). Most tasks showed moderate to substantial agreement, except a few with low agreement. Substantial to perfect agreement was observed for the duration of tasks, based on exact years of beginning and ending. CONCLUSION: Farmers' answers appeared reliable for most occupational data, including data used to assess individual exposure to specific pesticides, and for most potential confounders.

Occupational exposure to pesticides and multiple myeloma in the AGRICAN cohort.

PURPOSE: Epidemiological studies have found an increased risk of multiple myeloma (MM) in farmers. Few studies have investigated the detailed circumstances of occupational pesticide exposure which could explain these increased risks (pesticide use on crops, seeds or on animals, contact with treated crops) and the role of other exposures. In the Agriculture and Cancer cohort (AGRICAN), we assessed the associations between MM and crop- or animal-related activities, with specific attention to pesticide exposure via use on animals and crops or contact with treated crops and to disinfectant exposure. METHODS: Analyses concerned 155,192 participants, including 269 incident MM identified by cancer registries from enrolment (2005-2007) to 2013. Cox models using attained age as time scale were run to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: MM risk was increased in farmers (i) who started using pesticides on crops in the 1960s, especially among those applying pesticides on corn (≥ 20 years: HR 1.73, 95% CI 1.08, 2.78, p for trend < 0.01) and (ii) using insecticides on animals (HR 1.48, 95% CI 1.11, 1.98), especially among horse farmers (≥ 10 years: HR 2.77, 95% CI 1.22-6.27, p for trend = 0.01). We also observed significant elevated risks with disinfectant use in animal barns. CONCLUSIONS: Findings support the role of pesticide use on crops and animals in the occurrence of MM risk in farmers.

Lung cancer risk and occupational exposures in crop farming: results from the AGRIculture and CANcer (AGRICAN) cohort.

OBJECTIVES: Farmers are considered at lower risk of lung cancer. However, specific tasks can expose them to hazardous air contaminants such as pesticides, diesel exhaust and mineral dust. This study aimed to assess the associations between various crops and related tasks and the risk of lung cancer, overall and by histological subtypes. METHODS: AGRIculture and CANcer is a prospective French cohort of individuals affiliated to the agricultural health insurance scheme. Incident lung cancers (n=897) were identified by cancer registries from enrolment (2005-2007) to 2013. Data on crop and livestock exposure during lifetime were obtained from the enrolment questionnaire. We used a Cox model with attained age as timescale, adjusted for gender, smoking history and exposure to cattle and horses. Effects of duration and surface were assessed and analyses stratified on gender and smoking status were performed. RESULTS: Winegrowers were at higher risk of adenocarcinoma (HR=1.27 (95% CI 0.94 to 1.72)). We also found an association between pea growing and small cell lung cancer: significant effect of duration (ptrend=0.04) and the suggestion of a surface-effect relationship (ptrend=0.06); increased risk (HR=2.38 (95% CI 1.07 to 5.28)) for pesticide users; and significant effect of duration (ptrend=0.01) for harvesters. The risk of squamous cell carcinoma was increased for sunflower growing (HR=1.59 (95% CI 0.97 to 2.62), fruit-tree pruning (HR=1.44 (95% CI 0.92 to 2.27)) and pesticide use on beets (HR=1.47 (95% CI 0.92 to 2.34)). Corn and/or wheat/barley growers were at lower risk of lung cancer. CONCLUSIONS: Our results suggest associations between lung cancer and several crop-related tasks, even if we cannot rule out some chance findings due to multiple comparisons.

Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN.

Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (Agriculture & Cancer), we investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. Even if we cannot completely rule out the contribution of other factors, pesticide exposures could be of primary concern to explain these findings.

Exposure to Farm Animals and Risk of Lung Cancer in the AGRICAN Cohort.

Epidemiologic studies have found lower risks of lung cancer in farmers. However, little is known about the types of agricultural activities concerned. In the Agriculture and Cancer cohort, we assessed the relationship between animal farming and lung cancer by investigating the types of animals, tasks, and timing of exposure. Analyses included 170,834 participants from the Agriculture and Cancer (AGRICAN) cohort in France. Incident lung cancers were identified through linkage with cancer registries from enrollment (2005-2007) to 2011. A Cox model, adjusting for pack-years of cigarette smoking, was used to calculate hazard ratios and 95% confidence intervals. Lung cancer risk was inversely related to duration of exposure to cattle (≥40 years: hazard ratio = 0.60, 95% confidence interval: 0.41, 0.89; P for trend < 0.01) and to horse farming (≥20 years: hazard ratio = 0.64, 95% confidence interval: 0.35, 1.17; P for trend = 0.09), especially for adenocarcinomas, but not with poultry or pig farming. More pronounced decreased risks were reported among individuals who had cared for animals, undertaken milking, and who had been exposed to cattle in infancy. Our study provides strong evidence of an inverse association between lung cancer and cattle and horse farming. Further research is warranted to identify the etiologic protective agents and biological mechanisms.

Agricultural exposure and risk of bladder cancer in the AGRIculture and CANcer cohort.

PURPOSE: Literature on agricultural activities and bladder cancer risk is scarce. However, farmers can be subjected to carcinogenic exposure (e.g. arsenic, previously used as a pesticide in France). This study aimed at assessing the role of a large range of agricultural activities and tasks on bladder cancer risk. METHODS: The study population was the AGRIculture and CANcer cohort, a large prospective cohort of individuals affiliated to the agricultural health insurance scheme (MSA) in France. Incident bladder cancers were identified by cancer registries from enrolment (2005-2007) to 2009. Data on agricultural exposure during professional lifetime (5 animals, 13 crops, specific tasks) were obtained from the enrolment questionnaire. Associations between bladder cancer and agricultural exposure were analysed using a Cox model, adjusted for gender and smoking history. RESULTS: Among the 148,051 farm owners and workers included in this analysis, 179 incident bladder cancers were identified. We observed an elevated risk among field-grown vegetable workers [HR 1.89, 95% CI (1.20-2.99)], with an exposure-response relationship with duration of work [≥30 years: HR 2.54, 95% CI (1.11-5.83), p-trend = 0.02], and higher risk among women [HR 3.82, 95% CI (1.58-9.25), p-interaction = 0.05]. Non-significantly increased risks were also observed in greenhouse farmers (HR = 1.95), pea sowing (HR = 1.84), rape sowing (HR = 1.64); several tasks involving pesticide use, especially seed treatment (HR = 1.24); and in activities and tasks potentially exposing to arsenic compounds via pesticide use (HR = 1.49) or re-entry tasks (HR = 1.63). CONCLUSIONS: Our analyses raise the question of a possible link between agricultural activity, especially field-grown vegetables, and greenhouse cultivation and bladder cancer.

Breast Cancer Risk in Association with Atmospheric Pollution Exposure: A Meta-Analysis of Effect Estimates Followed by a Health Impact Assessment.

BACKGROUND: The epidemiological literature of associations between atmospheric pollutant exposure and breast cancer incidence has recently strongly evolved. OBJECTIVES: We aimed to perform a) a meta-analysis of studies considering this relationship, correcting for publication bias and taking menopausal status and cancer hormone responsiveness into account; and b) for the pollutants most likely to affect breast cancer, an assessment of the corresponding number of attributable cases in France and of the related economic costs. METHODS: We conducted a literature review and random-effects meta-analyses of epidemiological studies examining the association of fine particulate matter with aerodynamic diameter less than or equal to 2.5µm (PM2.5), particulate matter with aerodynamic diameter less than or equal to 10 µm (PM10), and NO2 long-term exposure with breast cancer incidence; additional analyses were stratified on menopausal status and on tumor hormone responsiveness status. The resulting dose-response functions were combined with modeled atmospheric pollutant exposures in 2013 for France, cancer treatments costs, lost productivity, and years of life lost, to estimate the number of breast cancers attributable to atmospheric pollution and related economic costs in France. RESULTS: The review identified 32, 27, and 36 effect estimates for PM2.5, PM10, and NO2, respectively. The meta-analytical relative risk estimates of breast cancer corrected for publication bias were 1.006 [95% confidence interval (CI): 0.941, 1.076], 1.047 (95% CI: 0.984, 1.113), and 1.023 (95% CI: 1.005, 1.041), respectively. NO2 estimated effects appeared higher in premenopausal than in postmenopausal women and higher for hormone responsive positive (ER+/PR+) than negative (ER-/PR-) breast cancers. Assuming a causal effect of NO2, we estimated that 1,677 (95% CI: 374, 2,914) new breast cancer cases were attributable to NO2 annually in France, or 3.15% (95% CI: 0.70, 5.48) of the incident cases. The corresponding tangible and intangible costs were estimated to be €825 million (low, high: 570, 1,080) per year. CONCLUSION: These findings suggest that decreasing long-term NO2 exposure or correlated air pollutant exposures could lower breast cancer risk. https://doi.org/10.1289/EHP8419.

Breast cancer risk in relation to ambient concentrations of nitrogen dioxide and particulate matter: results of a population-based case-control study corrected for potential selection bias (the CECILE study).

BACKGROUND: There is only scant evidence that air pollution increases the risk of breast cancer. OBJECTIVES: We investigated this relationship for three air pollutants: nitrogen dioxide (NO2) and particulate matter with an aerodynamical diameter below 10 µm (PM10) and 2.5 µm (PM2.5). METHODS: We conducted a population-based case-control study on breast cancer in two French départements, including 1,229 women diagnosed with breast cancer in 2005-2007 and 1,316 control women frequency-matched on age. Concentrations of NO2, PM10 and PM2.5 at participants' addresses occupied during the last 10 years were assessed using a chemistry transport model. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models where each woman was assigned a weight depending on her probability of selection into the study. RESULTS: The OR for breast cancer per 10-µg/m3 increase in NO2 was 1.11 (95% CI, 0.98, 1.26), and 1.41 (95% CI 1.07, 1.86) in the highest exposure quintile (Q5), compared to the first. The ORs per 10-µg/m3 NO2 did not markedly differ between pre- (OR 1.09, 95% CI 0.89, 1.35)) and post-menopausal women (OR 1.14, 95% CI 0.97, 1.33)), but the OR was substantially higher for hormone-receptor positive (ER+/PR+) breast tumor subtypes (OR 1.15, 95% CI 1.00, 1.31) than for ER-/PR- tumors (OR 0.95, 95% CI 0.72, 1.26). Breast cancer risk was not associated with either PM10 (OR per 1 µg/m3 1.01, 95% CI, 0.96, 1.06) or PM2.5 (OR per 1 µg/m3 1.02, 95% CI 0.95, 1.08), regardless of the menopausal status or of the breast tumor subtype. DISCUSSION: Our study provides evidence that NO2 exposure, a marker of traffic-related air pollutants, may be associated with an increased risk of breast cancer, particularly ER+/PR+ tumors.

Cancer incidence in the AGRICAN cohort study (2005-2011).

BACKGROUND: Numerous studies have been conducted among farmers, but very few of them have involved large prospective cohorts, and few have included a significant proportion of women and farm workers. Our aim was to compare cancer incidence in the cohort (overall, by sex, and by work on farm, occupational status and pesticide use) within the general population. METHODS: More than 180,000 participants in the AGRICAN cohort were matched to cancer registries to identify cancer cases diagnosed from enrolment (2005-2007) to 31st December 2011. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (95%CIs). RESULTS: Over the period, 11,067 incident cancer cases were identified (7304 men and 3763 women). Overall cancer incidence did not differ between the cohort and the general population. Moreover, SIRs were significantly higher for prostate cancer (SIR=1.07, 95%CI 1.03-1.11) and non-Hodgkin lymphoma (SIR=1.09, 95%CI 1.01-1.18) among men, skin melanoma among women (SIR=1.23, 95%CI 1.05-1.43) and multiple myeloma (men: SIR=1.38, 95%CI 1.18-1.62; women: SIR=1.26, 95%CI 1.02-1.54). In contrast, SIRs were lower for upper aerodigestive tract and respiratory cancers. Increase in risk was greater in male farm workers for prostate and lip cancer, in female farm workers for skin melanoma, and in male farm owners for multiple myeloma. Moreover, incidence of multiple myeloma and skin melanoma was higher among male and female pesticide users respectively. CONCLUSION: We found a decreased incidence for tobacco-related cancers and an increased incidence of prostate cancers, skin melanoma and multiple myeloma. Specific subgroups had a higher cancer incidence related to occupational status and pesticide use.

Prostate cancer risk among French farmers in the AGRICAN cohort.

OBJECTIVES: Prostate cancer is one of the most frequent cancers among men worldwide. Its etiology is largely unknown, but an increased risk has been repeatedly observed among farmers. Our aim was to identify occupational risk factors for prostate cancer among farmers in the prospective cohort study AGRICAN. METHODS: Data on lifetime agricultural exposures (type of crops, livestock and tasks including pesticide use, re-entry and harvesting) were collected from the enrolment questionnaire. During the period from enrolment (2005-2007) to 31 December 2009, 1672 incident prostate cancers were identified. Hazard ratios (HR) were estimated using Cox regression analysis. RESULTS: We found an increased risk for cattle breeders using insecticides [HR 1.20, 95% confidence interval (95% CI) 1.01-1.42] with a significant dose-response relationship with number of cattle treated (P for trend 0.01). A dose-response relationship was also observed with the number of hogs (P for trend 0.06). We found an excess of prostate cancer risk among people involved in grassland activities, mainly in haymaking (HR 1.18, 95% CI 1.02-1.36). Pesticide use and harvesting among fruit growers were associated with an elevated prostate cancer risk, with a two-fold increased risk for the largest area. For potato and tobacco producers, an elevated prostate cancer risk was observed for almost all tasks, suggesting a link with pesticide exposure since all of them potentially involved pesticide exposure. CONCLUSIONS: Our analysis suggests that the risk of prostate cancer is increased in several farming activities (cattle and hog breeding, grassland and fruit-growing) and for some tasks including pesticide use.