Animal farming and the risk of lymphohaematopoietic cancers: a meta-analysis of three cohort studies within the AGRICOH consortium.

OBJECTIVE: Animal farming entails a variety of potential exposures, including infectious agents, endotoxins and pesticides, which may play a role in the aetiology of lymphohaematopoietic cancers (LHCs). The aim of this study was to assess whether farming specific animal species is associated with the risk of overall LHC or its subtypes. METHODS: Data from three prospective cohort studies in the USA, France and Norway which are part of the Agricultural Cohort consortium and which collected information about animal farming and cancer were used. Analyses included 316 270 farmers and farm workers. Adjusted Cox models were used to investigate the associations of 13 histological subtypes of LHC (n=3282) with self-reported livestock (cattle, pigs and sheep/goats) and poultry (ever/never and numbers raised) farming. Cohort-specific HRs were combined using random-effects meta-analysis. RESULTS: Ever animal farming in general or farming specific animal species was not meta-associated with overall LHC. The risk of myeloid malignancies decreased with increasing number of livestock (p trend=0.01). Increased risk of myeloproliferative neoplasms was seen with increasing number of sheep/goats (p trend <0.01), while a decreased risk was seen with increasing number of livestock (p trend=0.02). Between cohorts, we observed heterogeneity in the association of type of animal farmed and various LHC subtypes. CONCLUSIONS: This large-scale study of three prospective agricultural cohorts showed no association between animal farming and LHC risk, but few associations between specific animal species and LHC subtypes were observed. The observed differences in associations by countries warrant further investigations.

Pesticide use and risk of non-Hodgkin lymphoid malignancies in agricultural cohorts from France, Norway and the USA: a pooled analysis from the AGRICOH consortium.

BACKGROUND: Pesticides are commonly used in agriculture, and previous studies endorsed the need to further investigate the possible association between their use and risk of lymphoid malignancies in agricultural workers. METHODS: We investigated the relationship of ever use of 14 selected pesticide chemical groups and 33 individual active chemical ingredients with non-Hodgkin lymphoid malignancies (NHL) overall or major subtypes, in a pooled analysis of three large agricultural worker cohorts. Pesticide use was derived from self-reported history of crops cultivated combined with crop-exposure matrices (France and Norway) or self-reported lifetime use of active ingredients (USA). Cox regression models were used to estimate cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs), which were combined using random effects meta-analysis to calculate meta-HRs. RESULTS: During follow-up, 2430 NHL cases were diagnosed in 316 270 farmers accruing 3 574 815 person-years under risk. Most meta-HRs suggested no association. Moderately elevated meta-HRs were seen for: NHL and ever use of terbufos (meta-HR = 1.18, 95% CI: 1.00-1.39); chronic lymphocytic leukaemia/small lymphocytic lymphoma and deltamethrin (1.48, 1.06-2.07); and diffuse large B-cell lymphoma and glyphosate (1.36, 1.00-1.85); as well as inverse associations of NHL with the broader groups of organochlorine insecticides (0.86, 0.74-0.99) and phenoxy herbicides (0.81, 0.67-0.98), but not with active ingredients within these groups, after adjusting for exposure to other pesticides. CONCLUSIONS: Associations of pesticides with NHL appear to be subtype- and chemical-specific. Non-differential exposure misclassification was an important limitation, showing the need for refinement of exposure estimates and exposure-response analyses.

Sick leave and medication use in pregnancy: a European web-based study.

BACKGROUND AND OBJECTIVE: A comparison of sick leave in pregnancy between countries is difficult as most studies have been conducted in single countries in Scandinavia. The objective of this study was to explore patterns of and reasons for sick leave during pregnancy on a multinational level, focusing on medication use but also differences in sick leave policies. DESIGN AND SETTING: Cross-sectional, web-based study in 12 European countries from October 2011 to February 2012. Data were collected via an electronic questionnaire. PARTICIPANTS: Pregnant women and mothers of children under the age of 1 year. PRIMARY OUTCOME MEASURE: Sick leave prevalence in pregnancy. RESULTS: Of 6686 women included, 3385 (50.6%) had been on sick leave during pregnancy. The rates of sick leave varied across countries, ranging from 31.7%-34.8% in Sweden and the UK to 62.4%-71.3% in Norway, Serbia, Croatia and Poland. The most common reasons for being on sick leave were pregnancy complications (26.5%); pain in the neck, back or pelvic girdle (16.2%); and nausea and vomiting (NVP, 16.0%). Women using medications for acute illnesses were more likely to be on sick leave than their non-medicated counterparts, while an opposite trend was observed for women with chronic disorders, where non-medicated women were more likely to be on sick leave. Women from countries with 'low' sick leave policies were less likely to have extensions of sick leaves compared with women from countries with 'medium' policies (adjusted OR 0.63, 95% CI 0.49 to 0.82). CONCLUSION: The rates of sick leave in pregnancy vary greatly across European countries. Women using medications were more likely to be on sick leave, especially for acute illnesses. The differences in sick leave patterns across countries only partially reflected differences in sick leave policies, which implies that sick leave in pregnancy is also affected by other national differences.

Airway inflammation and ammonia exposure among female Palestinian hairdressers: a cross-sectional study.

OBJECTIVES: Little is known about the working conditions and airway inflammation in hairdressers in Palestine. We aimed to investigate if hairdressers in Palestine have a higher level of airway inflammation as compared to a control group. We also assessed the hairdressers' physical working conditions and exposure to ammonia gases at the hair salons. Lastly, we investigated the association between ammonia levels and inflammation markers in the airways and the blood. METHODS: Our study participants were 33 non-smoking hairdressers (aged 19-50 years) and 35 non-smoking control subjects (aged 18-49 years). Both groups answered a questionnaire on respiratory symptoms, and performed lung function and exhaled nitric oxide (eNO) tests. Blood and sputum samples were collected from all participants and air concentration levels of ammonia were measured in 13 salons. RESULTS: Hairdressers had a higher level of sputum neutrophil count (absolute numbers/mg sputum (median (25th-75th centiles)) compared to controls, 376 (183-980) and 182 (96-358), respectively. Hairdressers also had significantly elevated eNO and blood C reactive protein (CRP) levels compared to the control subjects, controlled for age and body mass index. Exposure measurements showed that the hairdressers in salons with scarce ventilation were exposed to ammonia concentration, ranging from 3 to 61 mg/m(3). CONCLUSIONS: Compared to unexposed controls, the hairdressers had signs of neutrophilic airway inflammation, higher eNO levels and higher CRP. The hairdressers were exposed to high concentrations of ammonia from hairdressing chemicals and their working conditions were unsatisfactory.

Cross-Shift Changes in Lung Function Among Palestinian Farmers During High- and Low-Exposure Periods to Pesticides: A Longitudinal Study.

The purpose of this study was to study cross-shift changes of lung function in relation to pesticide use. One hundred and ninety-five male farmers, from a total of 250 farmers, performed lung function tests both pre- and post-shift during high- and low-pesticide-exposure periods. There were no associations between lung function differences across shifts and estimated quantity of pesticides used. However, the cross-shift reduction in forced expiratory volume in 1 second (FEV1; ΔFEV1) was more pronounced during the period when pesticides were used on a larger scale, September 2006, compared with the exposure period with a lower level of pesticide use, April 2007, +50 mL (95% confidence interval [CI]: +24, +76) and +17 mL (95% CI: -13, +48), respectively. This contrast was statistically significant only among the subset of never-smoking participants below 50 years of age. This finding suggests a possible obstructive effect of pesticide exposure on lung function among this rural male population in Palestine. A follow-up of farmers' lung function in this part of the world along with high-quality measurements of exposure is needed.

Life expectancy and cause of death in men examined at medical check-ups in 1964.

BACKGROUND: The purpose of the study was to determine the associations between blood pressure, body mass index and smoking habits, recorded at routine health check-ups with the occupational health officer, and life expectancy and cause-specific mortality through several decades. MATERIAL AND METHODS: Participants in the Linseed Oil Study were followed from 1967 through 2005 with respect to total and cause-specific mortality in the Cause of Death Registry. The population studied consisted of 15,934 men who were born between 1905 and 1914 and were in work in 1967. The analyses used various multivariate regression methods. RESULTS: A total of 15,535 participants (97.5%) had died, and the average age at death was 76.6 years (SD 9.1). Blood pressure, body mass index and cigarette smoking were related to the age of death and mortality due to cardiovascular disease, lung cancer and respiratory system diseases. High systolic blood pressure (≥ 160 mm) was associated with a life-expectancy shortening of 5 years, 15 cigarettes daily with 3.5 years and a confirmed elevated sedimentation rate with a 3.3 year shortening of life expectancy. The excess mortality persisted throughout the follow-up period. The association with blood pressure gradually lessened, while the association with smoking and body mass index did not change over time. The association with smoking was weaker than in most early studies. INTERPRETATION: The results of routine health check-ups in the occupational health service can predict lost years of life through several decades.

Pesticide use and opportunities of exposure among farmers and their families: cross-sectional studies 1998-2006 from Hebron governorate, occupied Palestinian territory.

BACKGROUND: Adverse health effects caused by pesticide exposure have been reported in occupied Palestinian territory and the world at large. The objective of this paper is to compare patterns of pesticide use in Beit-U'mmar village, West Bank, between 1998 and 2006. METHODS: We studied two populations in Beit-U'mmar village, comprised of: 1) 61 male farmers and their wives in 1998 and 2) 250 male farmers in 2006. Both populations completed a structured interview, which included questions about socio-demographic factors, types of farming tasks, as well as compounds, quantities, and handling of pesticides. Using the 1998 population as a reference, we applied generalized linear regression models (GLM) and 95% confidence intervals (CI) in order to estimate prevalence differences (PD) between the two populations. RESULTS: In 1998, farmers used 47 formulated pesticides on their crops. In 2006, 16 of these pesticides were still in use, including five internationally banned compounds. There were positive changes with less use of large quantities of pesticides (>40 units/year) (PD -51; CI -0.60, -0.43), in applying the recommended dosage of pesticides (PD +0.57; CI +0.48, +0.68) and complying with the safety period (PD +0.89; CI+0.83, +0.95). Changes also included farmers' habits while applying pesticides, such as less smoking (PD -0.20; CI-0.34, -0.07) and eating at the work place (PD -0.33; CI-0.47, -0.19). No significant changes were found from 1998 to 2006 regarding use of personal protective equipment, pesticide storage, farmers' habits after applying pesticides, and in using some highly hazardous pesticides. CONCLUSIONS: The results were based on two cross-sectional surveys and should be interpreted with caution due to potential validity problems. The results of the study suggest some positive changes in the handling of pesticides amongst participants in 2006, which could be due to different policy interventions and regulations that were implemented after 1998. However, farm workers in Beit -U'mmar village are still at risk of health effects because of ongoing exposure to pesticides. To the best of our knowledge, no studies on long-term changes in pesticide use have been reported from developing countries.

Dealing with emigration in cohort studies: follow-up of mortality and cancer incidence among Norwegians born between 1967 and 1976.

Emigration causes loss to follow-up. The study aim was to assess the influence of the choice of handling migration in population-based cohort studies on estimated mortality and cancer incidence in the population of origin. All persons born in Norway between 1967 and 1976 and who were not registered dead before 1992 (N = 614,176) were followed up in national registries regarding migration movements, death, and incident cancer between 1992 and 2004. A total of 40,366 (6.6%) of the study population had between 1 and 13 migration movements and 5,354 deaths and 4,447 first cancer cases were recorded during follow-up. Four different follow-up scenarios concerning migration were analysed: considering only person-time before emigration; considering person-time as national residents both before emigration and after repatriation; disregarding whether emigration took place or not; and excluding all who emigrated during follow-up. Mortality and cancer incidence rates were compared in Poisson regression models. Mortality and cancer incidence were only marginally influenced by choice of follow-up scenario. Mortality was higher after repatriation, in particular during the first year of follow-up (rate ratio 2.03; 95% confidence interval 1.02-4.03). This excess had little influence on total population rates. Cancer incidence was not affected by repatriation status. Mortality rates after repatriation were probably elevated because persons who expected to die shortly were more prone to return to their native country ("salmon bias"). The analytical choice concerning follow-up has little influence on outcome occurrences in populations with rather low migration rates. However, the best solution is apparently to censor out persons at the date of emigration in order to avoid salmon bias.

Incidence of lymphohaematopoietic cancer at a university laboratory: a cluster investigation.

We investigated a suspected cluster of lymphohaematopoietic cancer in departments of biology and chemistry at a Norwegian university. A historical cohort of students and employees (n = 7,189) were followed for cancer for 96,936 person-years in the Cancer Registry of Norway. Overall, 12 cases of lymphohaematopoietic cancer were identified, which was close to the expected number (standardised incidence ratio 1.1, 95% confidence interval (CI) 0.6-1.9). The SIR for leukaemia was 1.8 (95% CI 0.6-4.2) whereas incidences for non-Hodgkin lymphoma and Hodgkin's disease incidence were close to the expected. Distinct rate differences were observed in subgroups, and the strongest adjusted associations were found for Ph.D. students (rate ratio (RR) = 4.8, 95% CI 1.1-20.3) and students who participated in basic organic chemistry laboratory course (RR = 4.4, 95% CI 1.2-18.8). The latter category was identified a priori because it was the only student activity with known use of benzene according to the university administration. This is an observational study with some limitations, and hence, caution is warranted when drawing inferences on the causal relationship between university activities and cancers under study. The study provides an example that cluster investigations can answer questions of public importance despite a more limited value regarding causal inference.

Indicators of mancozeb exposure in relation to thyroid cancer and neural tube defects in farmers' families.

OBJECTIVES: The fungicide mancozeb has been suspected of causing thyroid cancer and neural tube defects. The aim of the study was to investigate associations of indicators of mancozeb exposure with thyroid cancer and neural tube defects in farmers' families. METHODS: National registers in Norway, identifying 105 403 female and 131 243 male farmers, born in 1925-1971, and their 300 805 children available for analyses, born in 1952-1991, were cross-linked with national agricultural censuses, 1969-1989, and the population register. Neural tube defects (ICD-8 740-742) at birth among the 102 703 children conceived between May 1973 and April 1991 were identified in the medical birth register. Likewise thyroid cancer (ICD-7 194) was identified in the cancer register through 2000. Data on farm production and fungal forecasts (humid and temperate weather conditions) in 1973-1990, obtained from agricultural censuses and meteorological measurement stations, respectively, served as the mancozeb exposure indicators. The adjusted rate ratio or prevalence ratio (PR) estimates with 95% confidence intervals (95% CI) were computed in a Poisson regression analysis. RESULTS: Neural tube defects (131 cases, prevalence 12.8/10 000 births) was moderately associated with potato cultivation (PR 1.6, 95% CI 1.1-2.3) and paternal work of > 500 hours/year (PR 1.6, 95% CI 1.1-2.5). Altogether 319 thyroid cancer cases were identified: 141 in female farmers (incidence 10.2/100 000 person-years), 79 in male farmers (incidence 3.2/100 000 person-years), and 99 in offspring (female and male incidence 3.4 and 0.6/100 000 person-years, respectively). Mancozeb exposure was not associated with thyroid cancer. CONCLUSIONS: A moderate association seems to exist between mancozeb exposure and neural tube defects, but not between mancozeb exposure and thyroid cancer.

Trichothecene mycotoxins and their determinants in settled dust related to grain production.

We hypothesise that inhalant exposure to mycotoxins causes developmental outcomes and certain hormone-related cancers that are associated with grain farming in an epidemiological study. The aim of the present study was to identify and validate determinants of measured trichothecene mycotoxins in grain dust as work environmental trichothecene exposure indicators. Settled grain dust was collected in 92 Norwegian farms during seasons of 1999 and 2000. Production characteristics and climatic data were studied as determinants of trichothecenes in settled dust samples obtained during the production of barley (N = 59), oats (N = 32), and spring wheat (N = 13). Median concentrations of trichothecenes in grain dust were <20, 54, and < 50 mg/kg (ranges < 20-340, < 30-2400, and < 50-1200) for deoxynivalenol (DON), HT-2 toxin (HT-2) and T-2 toxin (T-2) respectively. Late blight potato rot (fungal) forecasts have been broadcast in Norway to help prevent this potato disease. Fungal forecasts representing wet, temperate, and humid meteorological conditions were identified as strong determinants of trichothecene mycotoxins in settled grain dust in this study. Differences in cereal species, production properties and districts contributed less to explain mycotoxin concentrations. Fungal forecasts are validated as indicators of mycotoxin exposure of grain farmers and their use in epidemiological studies may be warranted.