Although the association between infection and childhood cancer has been long investigated, there is limited information on rarer cancers. This article aimed to explore the association between ...postnatal infection and childhood cancers in the Danish population. A matched case‐control study was conducted using Danish nationwide registries from 1978 to 2016. Each childhood cancer case was matched 1:25 with controls by birth date within a week and sex. Postnatal infections were identified from the Danish National Patient Registry, which lists diagnoses seen in hospital, specialist or emergency care services. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (adj.OR) and 95% confidence intervals (CI). Specific types of infections and the number of infection episodes were also considered. The study included 4125 childhood cancer cases and 103 526 matched controls with ages ranging from 0 to 19 years. Medically diagnosed postnatal infections were positively associated with many types of childhood cancer including acute lymphoblastic leukemia (adj.OR = 1.42; 95% CI: 1.23‐1.63), acute myeloid leukemia (adj.OR = 1.80; 95% CI: 1.28‐2.52), non‐Hodgkin lymphoma (adj.OR = 1.53; 95% CI: 1.19‐1.97) and central nervous system tumors (adj.OR = 1.57; 95% CI: 1.39‐1.77). A higher number of infection episodes were also associated with an increased risk of these cancers. Specific infections such as viral, enteric and urinary tract infections were also strongly associated with specific types of cancer. In conclusion, children who later develop cancer appear to have adverse reactions to infections necessitating referral to specialized health care services, perhaps indicating dysregulated immune function.
What's new?
Postnatal infection is suspected of being associated with childhood cancers, particularly leukemia. Associations between specific infection types and subtypes of childhood leukemia, however, remain unknown. Here, associations between postnatal infection and childhood cancers were assessed using data from the Danish National Patient Register. Investigation revealed positive associations between postnatal infections and various types of childhood cancer, including acute lymphoblastic leukemia, acute myeloid leukemia, non‐Hodgkin lymphoma and central nervous system tumors. Cancer risk increased with increasing number of infection episodes. Children who develop cancer may experience adverse reactions to infections that require specialized care, possibly indicating immune system dysregulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Nitrosatable drugs can be synthesized to N‐nitroso compounds in human stomach. In a pregnant woman, N‐nitroso compounds can be translocated to the fetus through the placenta. Maternal ...exposure of nitrosatable compounds during pregnancy has been associated with childhood brain tumors and leukemia. However, few studies have investigated an association between nitrosatable drug exposure during pregnancy and childhood cancer. We examined if maternal prescriptions of nitrosatable drugs received during pregnancy are associated with childhood cancer.
Methods
A matched case‐control study was conducted using Danish nationwide registry data from 1995 to 2016. Each childhood cancer case was matched with twenty‐five controls. Maternal exposure of nitrosatable drugs during pregnancy was identified from the Danish National Prescription Register. A multivariable conditional logistic regression model was used to estimate adjusted odds ratios (adj.OR) with 95% confidence intervals (CI) for each childhood cancer type.
Results
Maternal prescriptions of nitrosatable drugs positively associate with central nervous system tumors (adj.OR = 1.25; 95% CI = 1.04–1.51) and neuroblastoma (adj.OR = 1.96; 95% CI = 1.34–2.85) in offspring. We also observed a positive association between perinatal exposure of nitrosatable drugs and acute lymphoblastic leukemia (adj.OR = 1.31; 95% CI = 1.07–1.59), however, it appeared to be due to confounding by indication, i.e., maternal infections.
Conclusion
Nitrosatable drug use during pregnancy potentially increased risk of central nervous system tumors and neuroblastoma. While a positive association between maternal prescriptions of nitrosatable drugs and acute lymphoblastic leukemia should be interpreted cautiously because of confounding by indication.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and neurodevelopmental disorders. By utilizing high-resolution ...metabolomics (HRM), we investigated perturbations of the maternal serum metabolome in response to traffic-related air pollution to identify biological mechanisms.
We retrieved stored mid-pregnancy serum samples from 160 mothers who lived in the Central Valley of California known for high air particulate levels. We estimated prenatal traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 μm) during first-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) to select metabolic features associated with air pollution exposure. Pathway analyses were employed to identify biologic pathways related to air pollution exposure. As potential confounders we included maternal age, maternal race/ethnicity, and maternal education.
In total we extracted 4038 and 4957 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for confounding factors, PLS-DA (Variable Importance in Projection (VIP) ≥2) yielded 181 and 251 metabolic features (HILIC and C18, respectively) that discriminated between the high (n = 98) and low exposed (n = 62). Pathway enrichment analysis for discriminatory features associated with air pollution indicated that in maternal serum oxidative stress and inflammation related pathways were altered, including linoleate, leukotriene, and prostaglandin pathways.
The metabolomic features and pathways we found to be associated with air pollution exposure suggest that maternal exposure during pregnancy induces oxidative stress and inflammation pathways previously implicated in pregnancy complications and adverse outcomes.
•High-resolution metabolomics detected metabolic signals associated with air pollution in maternal mid-pregnancy serum.•High levels of air pollution in early pregnancy affected oxidative stress and inflammatory activities.•Metabolism derived markers pointed to mechanisms in which air pollution may cause adverse pregnancy and birth outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews ...have summarized the most recently published evidence and no analyses have examined the dose-response relation.
We investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia.
We searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model.
We found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels.
Overall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Pesticide exposures have been examined previously as risk factors for childhood brain cancers, but few studies were able to assess risk from specific agents.
To evaluate risks for childhood central ...nervous system tumors associated with residential proximity to agricultural pesticide applications.
Using the California Cancer Registry, we identified cancer cases less than 6 years of age and frequency matched them by year of birth to 20 cancer-free controls identified from birth certificates. We restricted analyses to mothers living in rural areas and births occurring between 1998 and 2011, resulting in 667 cases of childhood central nervous system tumors and 123,158 controls. Possible carcinogens were selected per the Environmental Protection Agency's (US. EPA) classifications, and prenatal exposure was assessed according to pesticides reported by the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system as being applied within 4000m of the maternal residence at birth. We computed odds ratios for individual pesticide associations using unconditional logistic and hierarchical regression models.
We observed elevated risks in the hierarchical models for diffuse astrocytoma with exposure to bromacil (OR: 2.12, 95% CI: 1.13–3.97), thiophanate-methyl (OR: 1.64, 95% CI: 1.02–2.66), triforine (OR: 2.38, 95% CI: 1.44–3.92), and kresoxim methyl (OR: 2.09, 95% CI: 1.03–4.21); elevated risks for medulloblastoma with exposure to chlorothalonil (OR: 1.78, 95% CI: 1.15–2.76), propiconazole (OR: 1.60, 95% CI: 1.02, 2.53), dimethoate (OR: 1.60, 95% CI: 1.06, 2.43), and linuron (OR: 2.52, 95% CI: 1.25, 5.11); and elevated risk for ependymoma with exposure to thiophanate-methyl (OR: 1.72, 95% CI: 1.10–2.68).
Our study suggests that exposure to certain pesticides through residential proximity to agricultural applications during pregnancy may increase the risk of childhood central nervous system tumors.
•A case-control study linking pesticides and childhood central nervous system tumors.•Those living near agricultural fields may experience effects of pesticide exposure.•Ambient pesticide exposure during pregnancy may increase cancer risk in offspring.•Medulloblastoma, ependymoma, and astrocytoma associated with specific pesticides.•Linuron, thiophanate-methyl, and triforine are possibly carcinogenic, among others.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objective
To examine environmental factors that influence risk of thyroid cancer.
Methods
We performed a case-control study utilizing thyroid cancer cases from the California Cancer Registry ...(1999-2012) and controls sampled in a population-based manner. Study participants were included if they were diagnosed with thyroid cancer, lived in the study area at their time of diagnosis, and were ≥35 years of age. Controls were recruited from the same area and eligible to participate if they were ≥35 years of age and had been living in California for at least 5 years prior to the interview. We examined residential exposure to 29 agricultural use pesticides, known to cause DNA damage in vitro or are known endocrine disruptors. We employed a validated geographic information system–based system to generate exposure estimates for each participant.
Results
Our sample included 2067 cases and 1003 controls. In single pollutant models and within a 20-year exposure period, 10 out of 29 selected pesticides were associated with thyroid cancer, including several of the most applied pesticides in the United States such as paraquat dichloride odds ratio (OR): 1.46 (95% CI: 1.23, 1.73), glyphosate OR: 1.33 (95% CI: 1.12, 1.58), and oxyfluorfen OR: 1.21 (95% CI: 1.02, 1.43). Risk of thyroid cancer increased proportionately to the total number of pesticides subjects were exposed to 20 years before diagnosis or interview. In all models, paraquat dichloride was associated with thyroid cancer.
Conclusions
Our study provides first evidence in support of the hypothesis that residential pesticide exposure from agricultural applications is associated with an increased risk of thyroid cancer.
Objectives Recent meta-analyses suggest a physical activity health paradox: high levels of occupational physical activity (OPA) increase cardiovascular disease (CVD) risk, while leisure-time physical ...activity (LTPA) decreases risk. However, studies of women and cerebrovascular disease are limited. This report examines physical activity effects on stroke and transient ischemic attack (TIA) among working women in the United States. Methods OPA history, health status, and lifestyle were assessed by baseline interviews of 31 270 employed Sister Study participants aged 35-74 years. OPA was assessed at six intensity levels (lowest: "mostly sitting"); the highest three were combined as "high intensity work." Independent OPA and LTPA effects on 6-year cerebrovascular disease incidence were estimated in adjusted Cox proportional hazard models. Results Stroke (N=441) and TIA (N=274) risk increased with more standing and higher intensity work at current and longest held job. Compared with mostly sitting, high intensity work at the current job increased TIA risk by 57% hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.04-2.38. High intensity OPA at the longest held job increased risk for stroke by 44% (HR 1.44; 95% CI 1.08-1.93). Among women with CVD, sitting and standing equally, especially at the current job, increased risks up to two-fold (TIA HR 1.98, 95% CI 1.10-3.55) compared with mostly sitting at work. LTPA showed inverse associations. Conclusions Higher intensity levels of OPA increased stroke and TIA risks, while LTPA decreased risks; results corroborate the physical activity health paradox for women and cerebrovascular disease. More standing at work increased cerebrovascular disease risks, especially for women with CVD.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, UL, UM, UPUK
A number of epidemiologic studies with a variety of exposure assessment approaches have implicated pesticides as risk factors for childhood cancers. Here we explore the association of pesticide ...exposure in pregnancy and early childhood with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) utilizing land use and pesticide use data in a sophisticated GIS tool.
We identified cancer cases less than 6 years of age from the California Cancer Registry and cancer-free controls from birth certificates. Analyses were restricted to those living in rural areas and born 1998–2011, resulting in 162 cases of childhood leukemia and 9,805 controls. Possible carcinogens were selected from the Environmental Protection Agency's classifications and pesticide use was collected from the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system and linked to land-use surveys. Exposures for subjects were assessed using a 4000m buffer around the geocoded residential addresses at birth. Unconditional logistic and hierarchical regression models were used to assess individual pesticide and pesticide class associations.
We observed elevated risks for ALL with exposure to any carcinogenic pesticide (adjusted Odds Ratio (aOR): 2.83, 95% CI: 1.67–4.82), diuron (Single-pesticide model, adjusted (OR): 2.38, 95% CI: 1.57–3.60), phosmet (OR: 2.10, 95% CI: 1.46–3.02), kresoxim-methyl (OR: 1.77, 95% CI: 1.14–2.75), and propanil (OR: 2.58, 95% CI: 1.44–4.63). Analyses based on chemical classes showed elevated risks for the group of 2,6-dinitroanilines (OR: 2.50, 95% CI: 1.56–3.99), anilides (OR: 2.16, 95% CI: 1.38–3.36), and ureas (OR: 2.18, 95% CI: 1.42–3.34).
Our findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Alpha-1 antitrypsin deficiency (AATD) is related to developing lung and liver disease, but no large-scale studies examine its association with birth outcomes.
We investigated the risk of pregnancy ...complications and adverse birth outcomes in mothers and children with AATD.
Using a large cohort data of Danish mothers and children with AATD from 1973 to 2013 (n = 2,027,229), with 559 cases (305 mothers and 254 children). We conducted Poisson regression to examine associations between alpha-1 antitrypsin deficiency, adverse birth outcomes, and pregnancy complications in mothers and children.
AATD was related to term low birth weight <2500g; Risk Ratio(RR) = 2.04, 95% confidence interval (CI): 1.50-2.79, lowest quartile of abdominal circumference at birth in children of non-smoking mothers (RR = 1.55, 95% CI: 1.14-2.11), delivery via Cesarean-section (RR = 1.59, 95% CI: 1.05-2.40), preterm birth (RR = 1.54, 95% CI: 1.19-2.00) and preeclampsia (RR = 2.64, 95% CI: 1.76-3.94).
This emphasizes the need for mothers with AATD to be monitored closely during pregnancy to reduce the risk of adverse birth outcomes. Routine screening for alpha-1 antitrypsin in pregnancy may be considered among mothers with a pulmonary and liver disease history.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK