Parental occupational exposure to metals and risk of cancer in the offspring: A register-based case-control study from Sweden.

BACKGROUND: Cancer risks in the offspring of mothers and fathers exposed to metals are unknown. We estimated the relative risks of childhood cancer, overall and by type, associated with parental occupational exposure to arsenic, cadmium, chromium, nickel, and lead. METHODS: We conducted a nested case-control study (1960-2015) of children born in Sweden aged 0-19 years diagnosed with cancer (National Cancer Register) matched 25:1 to controls on birth year and sex. We obtained parental occupational data around their birth from censuses and a nationwide register and identified exposure to each metal (yes/no, or higher/lower/no exposure) using the Swedish job-exposure matrix (SWEJEM). Adjusted odds ratios (OR) and 95% confidence intervals (CIs) were estimated separately for maternal and paternal exposures using conditional logistic regression. RESULTS: We compared 9653 cases to 1,72,194 controls in maternal and 12,521 cases to 2,74,434 controls in paternal analyses, respectively. We found a 38% increased risk of cancer associated with maternal occupational exposure to arsenic (OR 1.38 [95% CI 1.06, 1.82]), likely driven by higher risks for lymphoma (OR 1.52 [0.73, 3.15]), central nervous system (CNS) (OR 1.49 [0.88, 2.54]) and other solid malignancies (OR 1.74 [1.14, 2.65]). There were also indications of higher risks of lymphoma in children of mothers exposed to nickel and iron, and of CNS tumours due to chromium exposure. No associations were observed from paternal occupational exposure to any of the metals. CONCLUSIONS: We found evidence of increased risks of cancer in children of mothers but not fathers occupationally exposed to arsenic and potentially other metals.

Sarcoidosis: Epidemiology and clinical insights.

Sarcoidosis is characterized by noncaseating granulomas which form in almost any part of the body, primarily in the lungs and/or thoracic lymph nodes. Environmental exposures in genetically susceptible individuals are believed to cause sarcoidosis. There is variation in incidence and prevalence by region and race. Males and females are almost equally affected, although disease peaks at a later age in females than in males. The heterogeneity of presentation and disease course can make diagnosis and treatment challenging. Diagnosis is suggestive in a patient if one or more of the following is present: radiologic signs of sarcoidosis, evidence of systemic involvement, histologically confirmed noncaseating granulomas, sarcoidosis signs in bronchoalveolar lavage fluid (BALF), and low probability or exclusion of other causes of granulomatous inflammation. No sensitive or specific biomarkers for diagnosis and prognosis exist, but there are several that can be used to support clinical decisions, such as serum angiotensin-converting enzyme levels, human leukocyte antigen types, and CD4 Vα2.3+ T cells in BALF. Corticosteroids remain the mainstay of treatment for symptomatic patients with severely affected or declining organ function. Sarcoidosis is associated with a range of adverse long-term outcomes and complications, and with great variation in prognosis between populations. New data and technologies have moved sarcoidosis research forward, increasing our understanding of the disease. However, there is still much left to be discovered. The pervading challenge is how to account for patient variability. Future studies should focus on how to optimize current tools and develop new approaches so that treatment and follow-up can be targeted to individuals with more precision.

Occupational exposure to pesticides in mothers and fathers and risk of cancer in the offspring: A register-based case-control study from Sweden (1960-2015).

Maternal and paternal occupational exposure to pesticides was linked to leukemia in the offspring in some previous studies. Risks for other cancers, particularly from maternal exposure, are largely unknown. We examined the association between maternal and paternal exposure to pesticides and childhood cancer in a Swedish register-based case-control study (1960-2015). Cancer cases <20 years old were identified from the Cancer Register (n = 17313) and matched to controls (1:25) on birth year and sex. Employment history of each biological parent around the child's birth was retrieved from six censuses and a nationwide register, and exposure to any of herbicides, insecticides, and fungicides was evaluated using the Swedish job-exposure matrix (SWEJEM) in 9653/172194 mothers and 12521/274434 fathers of cases/controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models for any cancer, leukemia, lymphoma, central nervous system [CNS], and other solid tumors. We found an OR of 1.42 (95% CI 0.78, 2.57; 12 exposed cases) for lymphoma and 1.30 (95% CI 0.88, 1.93; 27 exposed cases) for other solid tumors associated with maternal occupational exposure to pesticides. No associations were observed between maternal exposure and leukemia or CNS tumors, or paternal exposure and any of the cancers examined, except for a potential association between pesticides exposure and myeloid leukemia (OR 1.15 [95% CI 0.73, 1.79; 22 exposed cases]). Although these findings merit further investigation, they indicate that parental exposure to pesticides may lead to higher risks of childhood cancer even in settings of low exposure.

Risk of Cancer in Children of Parents Occupationally Exposed to Hydrocarbon Solvents and Engine Exhaust Fumes: A Register-Based Nested Case-Control Study from Sweden (1960-2015).

BACKGROUND: It remains unclear whether parental occupational exposure to hydrocarbon solvents (HCS) or engine exhaust fumes (EEF) is associated with higher risks of cancer in the offspring. OBJECTIVES: Our aim was to estimate relative risks of childhood cancers associated with maternal or paternal exposure to aliphatic/alicyclic, aromatic, or chlorinated HCS or gasoline/diesel EEF. METHODS: We conducted a case-control study in which individuals <20y old, born 1960-2014, were identified from the Swedish National Cancer Register (1960-2015) at first cancer diagnosis and matched to population controls (1 case:25 controls) on birth year and sex. Maternal and paternal occupation around the child's birth was retrieved for 9,653 cases and 172,194 controls and 12,521 cases and 274,434 controls, respectively, using information from six censuses and a nationwide register. Using the Swedish job-exposure matrix (SWEJEM), we assessed exposure to HCS and EEF (any or higher/lower). Odds ratios (ORs) and 95% confidence intervals (CIs) of 15 childhood cancer subtypes were estimated using conditional logistic regression models adjusted for several confounders. RESULTS: Maternal exposure to aromatic HCS was associated with non-Hodgkin lymphoma (OR=1.64; 95% CI: 1.05, 2.58), aliphatic/alicyclic HCS with germ cell tumors (OR=1.52; 95% CI: 0.89, 2.59), and gasoline/diesel EEF with astrocytoma (OR=1.40; 95% CI: 1.04, 1.88), myeloid leukemia (OR=1.53; 95% CI: 0.84, 2.81), lymphomas (OR=1.60; 95% CI: 0.85, 3.02 for Hodgkin; OR=1.44; 95% CI: 0.71, 2.91 for non-Hodgkin), and epithelial tumors (OR=1.51; 95% CI: 0.93, 2.44). Paternal exposure to gasoline EEF was associated with Hodgkin lymphoma (OR=1.21; 95% CI: 1.01, 1.44) and soft tissue sarcomas (OR=1.22; 95% CI: 1.00, 1.48). No notable difference was observed between higher and lower exposure. DISCUSSION: Our findings suggest that occupational exposure to HCS or EEF, especially in the mother, may increase the risk of some childhood cancers. They add to the growing literature on adverse effects from HCS and EEF in the child, but replication of these associations in other populations is warranted. https://doi.org/10.1289/EHP11035.

Childhood cancer risk in offspring of parents occupationally exposed to dusts: A register-based nested case-control study from Sweden of 5 decades.

BACKGROUND: Some largely inconsistent associations between parental occupational dust exposure and childhood cancer have been reported, with maternal exposures inadequately studied. The authors examined whether maternal or paternal occupational exposure to animal, wood, textile, or paper dust around a child's birth was associated with an increased risk of childhood cancer, both overall and by type (leukemias, lymphomas, central nervous system tumors, and other cancers). METHODS: In this nationwide, register-based, case-control study, children who were diagnosed with cancer from 1960 to 2015 were compared with up to 25 matched controls regarding maternal and paternal occupational dust exposure (9653 cases in maternal analyses and 12,521 cases in paternal analyses). Exposures were assessed using a job-exposure matrix and occupational information from census and register data. By using conditional logistic regression models, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Neither maternal nor paternal occupational exposure to animal, wood, textile, or paper dust was associated with childhood cancer overall, leukemias, or central nervous system tumors. Maternal, but not paternal, wood dust exposure was associated with an increased risk of lymphoma (OR, 1.42; 95% CI, 1.10-1.84), particularly non-Hodgkin lymphoma (OR, 2.03; 95% CI, 1.21-3.40). CONCLUSIONS: The current study did not confirm the associations reported previously but is the first to suggest a link between maternal occupational exposure to wood dust around pregnancy and lymphoma in the offspring.

Maternal and infant outcomes in sarcoidosis pregnancy: a Swedish population-based cohort study of first births.

BACKGROUND: It is unclear whether sarcoidosis, a multisystem inflammatory disease, is associated with adverse pregnancy outcomes. We aimed to assess the risk of adverse maternal and infant outcomes in sarcoidosis pregnancies, focused on first births. METHODS: Using a population-based cohort study design and Swedish national registers (2002-2013), we identified 182 singleton first pregnancies in the Medical Birth Register with at least two maternal ICD-coded sarcoidosis visits prior to pregnancy in the National Patient Register. Modified Poisson regression models estimated relative risks (RR) of adverse outcomes in sarcoidosis pregnancies compared to the general population adjusted for maternal age at delivery, calendar year and educational level. Some models were additionally adjusted for maternal body mass index and smoking status. RESULTS: The prevalence of pre-existing diabetes and hypertension was higher in mothers with sarcoidosis than those without sarcoidosis. Mothers with sarcoidosis had an increased risk of preeclampsia/eclampsia (RR 1.6; 95%CI 1.0, 2.6) and cesarean delivery (RR 1.3; 95%CI 1.0, 1.6). There were < 5 stillbirths and cases of infection and no cases of placental abruption, venous thromboembolism, cardiac arrest or maternal death. Newborns of first-time mothers with sarcoidosis had a 70% increased risk of preterm birth (RR 1.7; 95%CI 1.1, 2.5). There was an increased risk of birth defects (RR 1.6; 95%CI 0.9, 2.8) the majority of which were non-cardiac. CONCLUSIONS: Sarcoidosis is associated with increased risks for preeclampsia/eclampsia, cesarean delivery, preterm birth and some birth defects. Awareness of these conditions may prevent possible pregnancy complications in mothers with sarcoidosis and their newborns.

New-onset non-infectious pulmonary manifestations among patients with systemic lupus erythematosus in Sweden.

OBJECTIVE: The objective was to estimate the incidence of lung disease among patients with systemic lupus erythematosus (SLE). METHODS: Using Swedish register data, we identified patients with SLE and pulmonary diagnoses from the National Patient Register through ICD codes. We matched patients with SLE with individuals from the general population. Patients with SLE with a history of pulmonary disease were excluded. Incidence rates (IR) and 95% confidence intervals (CI) were calculated overall and by type of pulmonary disease for incident (2003-2013) and prevalent SLE separately. Hazard ratios (HR) and 95% CI of the association between SLE and pulmonary disease were estimated using adjusted Cox regression models. Sensitivity analyses using a semi-automated approach to quantitative probabilistic bias analysis accounted for potential bias due to unmeasured confounding by smoking. RESULTS: There were 3209 incident and 6908 prevalent cases of SLE identified. The IRs for pulmonary disease were similar in prevalent and incident SLE (∼14 cases per 1000 person-years). Patients with incident SLE had a nearly sixfold higher rate of pulmonary disease compared to the non-SLE population (HR 5.8 (95% CI 4.8-7.0)). Incident and prevalent SLE was associated with an increased rate of interstitial lung disease (HR 19.0 (95% CI 10.7-34.0) and 14.3 (95% CI 10.8-18.8), respectively). Bias due to unmeasured confounding by smoking was unlikely to explain our findings. CONCLUSION: Lung disease is relatively common in patients with SLE compared to the general population. Clinicians caring for patients with SLE should have heightened suspicion of lung disease, including interstitial lung disease, even early within the disease course or at the time of diagnosis of SLE.

Do Death Certificates Underestimate the Burden of Rare Diseases? The Example of Systemic Lupus Erythematosus Mortality, Sweden, 2001-2013.

OBJECTIVES: Mortality due to rare diseases, which are substantial sources of premature mortality, is underreported in mortality studies. The objective of this study was to determine the completeness of reporting systemic lupus erythematosus (SLE) as a cause of death. METHODS: In 2017, we linked data on a Swedish population-based cohort (the Swedish Lupus Linkage, 2001-2013) comprising people with SLE (n = 8560) and their matched general population comparators (n = 37 717) to data from the Cause of Death Register. We reviewed death records of deceased people from the cohort (n = 5110) and extracted data on patient demographic characteristics and causes of death. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for not reporting SLE as a cause of death by using multivariable-adjusted logistic regression models. RESULTS: Of 1802 deaths among SLE patients in the study, 1071 (59%) did not have SLE reported on their death records. Most SLE decedents were aged 75-84 at death (n = 584, 32%), female (n = 1462, 81%), and born in Nordic countries (n = 1730, 96%). Decedents aged ≥85 at death were more likely to have SLE not reported on their death records than were decedents aged <50 (OR = 2.34; 95% CI, 1.48-3.68). Having renal failure listed as a cause of death decreased the likelihood of SLE not being reported on the death record (OR = 0.54; 95% CI, 0.40-0.73), whereas having cancer listed as a cause of death increased this likelihood (OR = 2.39; 95% CI, 1.85-3.07). CONCLUSIONS: SLE was greatly underreported as a cause of mortality on death records of SLE patients, particularly in older decedents and those with cancer, thereby underestimating the true burden of this disease. Public health resources need to focus on improving the recording of rare diseases in order to enhance the epidemiological utility of mortality data.

Asthma in Children of Mothers With Systemic Lupus Erythematosus and the Role of Preterm Birth.

OBJECTIVE: Systemic lupus erythematosus (SLE) and asthma share inheritable IgE-related pathophysiology, but the association between maternal SLE and asthma in the offspring has not been explored. Our aim was to investigate the association between maternal SLE during pregnancy and childhood asthma and examine the role of preterm birth as a mediator of the association using Swedish register data. METHODS: Information on 12,000 singleton live births (2001-2013) was collected from the Medical Birth Register. Childhood asthma was defined as at least 1 International Classification of Diseases-coded visit in the National Patient Register. Prevalent maternal SLE at delivery was identified from the Medical Birth Register and the National Patient Register. Risk ratios for asthma were estimated while controlling for confounders. Mediation analysis was used to estimate what percentage of the total effect can be explained by preterm birth (defined as either <34 or <37 weeks of gestation). RESULTS: We compared 775 children born to mothers with SLE with 11,225 born to mothers without SLE. Ninety seven children of mothers with SLE (13%) were diagnosed with asthma, compared to 1,211 in the unexposed group (11%). The risk ratio for childhood asthma was 1.46 (95% confidence interval 1.16-1.84). In mediation analysis, 20-29% of the total effect of SLE was explained by preterm birth. CONCLUSION: Prevalent maternal SLE during pregnancy is associated with an increased risk of asthma in the offspring. While preterm birth can explain a fair proportion of this association, additional unidentified mechanisms also likely play a role.