Ingestion of Nitrate and Nitrite and Risk of Stomach and Other Digestive System Cancers in the Iowa Women's Health Study.

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC) which are potent animal carcinogens for the organs of the digestive system. We evaluated dietary intakes of nitrate and nitrite, as well as nitrate ingestion from drinking water (public drinking water supplies (PWS)), in relation to the incidence (1986-2014) of cancers of the esophagus (n = 36), stomach (n = 84), small intestine (n = 32), liver (n = 31), gallbladder (n = 66), and bile duct (n = 58) in the Iowa Women's Health Study (42,000 women aged from 50 to 75 in 1986). Dietary nitrate and nitrite were estimated using a food frequency questionnaire and a database of nitrate and nitrite levels in foods. Historical nitrate measurements from PWS were linked to the enrollment address by duration. We used Cox regression to compute hazard ratios (HR) and 95% confidence intervals (CI) for exposure quartiles (Q), tertiles (T), or medians, depending on the number of cancer cases. In adjusted models, nitrite intake from processed meats was associated with an increased risk of stomach cancer (HRQ4vsQ1 = 2.2, CI: 1.2-4.3). A high intake of total dietary nitrite was inversely associated with gallbladder cancer (HRQ4vsQ1 = 0.3, CI: 0.1-0.96), driven by an inverse association with plant sources of nitrite (HRQ4vsQ1 = 0.3, CI: 0.1-0.9). Additionally, small intestine cancer was inversely associated with a high intake of animal nitrite (HRT3vsT1 = 0.2, CI: 0.1-0.7). There were no other dietary associations. Nitrate concentrations in PWS (average, years ≥ 1/2 the maximum contaminant level) were not associated with cancer incidence. Our findings for stomach cancer are consistent with prior dietary studies, and we are the first to evaluate nitrate and nitrite ingestion for certain gastrointestinal cancers.

Impact of residential mobility on estimated environmental exposures in a prospective cohort of older women.

Longitudinal studies of environmental hazards often rely on exposure estimated at the participant's enrollment residence. This could lead to exposure misclassification if participants move over time. METHODS: We evaluated residential mobility in the Iowa Women's Health Study (age 55-69 years) over 19 years of follow-up (1986-2004). We assessed several environmental exposures of varying spatial scales at enrollment and follow-up addresses. Exposures included average nitrate concentrations in public water supplies, percent of agricultural land (row crops and pasture/hay) within 750 m, and the presence of concentrated animal feeding operations within 5 km. In comparison to gold standard duration-based exposures averaged across all residences, we evaluated the sensitivity and specificity of exposure metrics and attenuation bias for a hypothetical nested case-control study of cancer, which assumed participants did not move from their enrollment residence. RESULTS: Among 41,650 participants, 32% moved at least once during follow-up. Mobility was predicted by working outside the home, being a former/current smoker, having a higher education level, using a public drinking water supply, and town size of previous residence. Compared with duration-based exposures, the sensitivity and specificity of exposures at enrollment ranged from 94% to 99% and 97% to 99%, respectively. A hypothetical true odds ratio of 2.0 was attenuated 8% for nitrate, 9%-10% for agricultural land, and 6% for concentrated animal feeding operation exposures. CONCLUSIONS: Overall, we found low rates of mobility and mobility-related exposure misclassification in the Iowa Women's Health Study. Misclassification and attenuation of hypothetical risk estimates differed by spatial variability and exposure prevalence.

Residential proximity to agriculture and risk of childhood leukemia and central nervous system tumors in the Danish national birth cohort.

BACKGROUND: Living in an agricultural area or on farms has been associated with increased risk of childhood cancer but few studies have evaluated specific agricultural exposures. We prospectively examined residential proximity to crops and animals during pregnancy and risk of childhood leukemia and central nervous system (CNS) tumors in Denmark. METHODS: The Danish National Birth Cohort (DNBC) consists of 91,769 pregnant women (96,841 live-born children) enrolled in 1996-2003. For 61 childhood leukemias and 59 CNS tumors <15 years of age that were diagnosed through 2014 and a ~10% random sample of the live births (N = 9394) with geocoded addresses, we linked pregnancy addresses to crop fields and animal farm locations and estimated the crop area (hectares [ha]) and number of animals (standardized by their nitrogen emissions) by type within 250 meters (m), 500 m, 1000 m, and 2000 m of the home. We also estimated pesticide applications (grams, active ingredient) based on annual sales data for nine herbicides and one fungicide that were estimated to have been applied to >30% of the area of one or more crop. We used Cox proportional hazard models (weighted to the full cohort) to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of childhood leukemia and CNS tumors with crop area, animals, and pesticide applications adjusted for gender and maternal age. RESULTS: Sixty-three percent of mothers had crops within 500 m of their homes during pregnancy; winter and spring cereals were the major crop types. Compared to mothers with no crops <500 m, we found increasing risk of childhood leukemia among offspring of mothers with increasing crop area near their home (highest tertile >24 ha HR: 2.0, CI:1.02-3.8), which was stronger after adjustment for animals (within 1000 m) (HR: 2.6, CI:1.02-6.8). We also observed increased risk for grass/clover (highest tertile >1.1 ha HR: 3.1, CI:1.2-7.7), peas (>0 HR: 2.4, CI: 1.02-5.4), and maize (>0 HR: 2.8, CI: 1.1-6.9) in animal-adjusted models. We found no association between number of animals near homes and leukemia risk. Crops, total number of animals, and hogs within 500 m of the home were not associated with CNS tumors but we observed an increased risk with >median cattle compared with no animals in crop-adjusted models (HR = 2.2, CI: 1.02-4.9). In models adjusted for total animals, the highest tertiles of use of three herbicides and one fungicide were associated with elevated risk of leukemia but no associations were statistically significant; there were no associations with CNS tumors. CONCLUSIONS: Risk of childhood leukemia was associated with higher crop area near mothers' homes during pregnancy; CNS tumors were associated with higher cattle density. Quantitative estimates of crop pesticides and other agricultural exposures are needed to clarify possible reasons for these increased risks.

Parental occupational exposure to pesticides, animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C).

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

Livestock and poultry density and childhood cancer incidence in nine states in the USA.

BACKGROUND: Parental occupational and childhood exposures to farm animals have been positively associated with childhood brain tumors, whereas associations with childhood leukemia are equivocal. The developing immune system may be influenced by allergen, virus, or other exposures from animal sources, which may contribute to childhood cancer incidence. METHODS: Incident cancers (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], central nervous system [CNS], peripheral nervous system [PNS]) for children aged 0-4 diagnosed between 2003 and 2008 were obtained from nine National Cancer Institute Surveillance, Epidemiology and End Results (SEER) registries and were linked to U.S. Census of Agriculture data from 2002 and 2007 by county of diagnosis. Animal densities (animal units [AU]/km2; one animal unit is 1000 pounds of animal weight) were estimated for hogs, cattle, chickens (layers and broilers, separately), equine (horses, ponies, mules, burros, donkeys), goats, sheep, turkeys, and total animals. Animal density was examined in models as both continuous (AU per km2) and categorical variables (quartiles). Animal operation densities (per km2) by size of operation (cattle, hogs, chickens, sheep) were modeled continuously. Rate ratios and 95% confidence intervals were estimated using Poisson regression. RESULTS: We found positive associations between AML and broiler chicken densities (RRper 10AU/km2 = 1.14, 95% CI = 1.02-1.26). ALL rates increased with densities of hog operations (RRper operation/100km2 = 1.06, 95% CI = 1.02-1.11). PNS cancer rates were inversely associated with layer chicken density (RRper log of AU/km2 = 0.94, 95% CI = 0.89-0.99). No association was found between any cancer type and densities of cattle, equine, or goats. CONCLUSIONS: Although limited by the ecologic study design, some of our findings are novel and should be examined in epidemiological studies with individual level data.