Occupational Epidemiology in Vulnerable Populations: Occupational Physical Activity and Cerebrovascular Disease in Older Women and Parental Occupational Exposures and Childhood Cancer

摘要

Occupation has a profound impact on worker health. Some working populations, such as older workers and pregnant women, are inherently vulnerable to hazardous exposures; identifying and quantifying occupational risk factors in these populations is important to the health and wellbeing of the population as a whole. This dissertation is composed of three independent exercises in occupational epidemiology that examine associations between (1) occupational physical activity and cerebrovascular disease in a cohort of older women; (2) parental occupational exposure to livestock or animal dust and the risk for childhood cancer in offspring; and (3) parental occupation and the risk for childhood germ cell tumors in Denmark.;The first analysis in this dissertation is a prospective cohort study of 31,270 women aged 30--74 years and employed outside the home at study enrollment. Information on occupational physical activity (OPA) for current job, longest held job, and cumulatively for all jobs held since age 18, in addition to information on lifestyle factors, was assessed via interviews at study enrollment. After classifying OPA into four categories ranked by intensity (mostly sitting, sitting and standing equally, mostly standing, and mostly dynamic work), we used Cox proportional hazard regression models adjusted for socio-demographic, biologic, and behavioral factors to estimate the risk of incident stroke and transient ischemic attack (TIA) across levels of OPA. There were 715 incident diagnoses of stroke (n=441) and TIA (n=274) reported by participants or next of kin over an average follow up of 6 years. Compared to mostly sitting, mostly dynamic OPA at the current job was associated with an increased risk for TIA (hazards ratio [HR]=1.65; 95% confidence interval [CI]=1.07-2.48), while mostly dynamic OPA at the longest held job was associated with an increased risk of stroke (HR=1.45; 95% CI=1.06-1.97). Associations were stronger among women without cardiovascular disease or hypertension at baseline.;The second analysis in this dissertation is a population-based case-control study of 4,474 childhood cancer cases diagnosed 1968--2015 in Denmark and 422,022 birth year- and sex-matched controls. Using a job-exposure matrix, we identified parental occupational exposure to livestock or animal dust. Using multivariable conditional logistic regression, we estimated an increased risk for all central nervous system tumors in the offspring of fathers occupationally exposed to livestock or animal dust from the index child's birth to cancer diagnosis (odds ratio [OR]=1.27; 95% CI=1.00-1.63). There was an increased risk for astrocytoma in the offspring of mothers exposed from conception to birth (OR=1.89; 95% CI=1.00-3.57) and an increased risk for neuroblastoma in the offspring of mothers exposed from birth to diagnosis (OR=1.88; 95% CI=0.99-3.56). We examined births 1989+ to assess a period when exposures were more intensive due to a policy change regulating farm size and estimated a decreased risk for acute lymphoblastic leukemia in the offspring of fathers exposed after birth (OR=0.56; 95% CI=0.32-1.00).;The final analysis in this dissertation is a population-based case-control study of parental occupation and the risk for childhood germ cell tumors (GCTs) in offspring. Utilizing a linked database of five nationwide Danish registries, this study consisted of 164 childhood GCT cases (<17 years old) diagnosed 1968--2015 and 15,513 birth year- and sex-matched controls. Conditional multivariable logistic regression was used to analyze the association between paternal and maternal occupation and childhood GCT risk in offspring, stratifying by common histologic subtypes (i.e., yolk sac tumor and teratoma) when possible. Parental occupational exposure to specific chemicals and social contact was assessed via JEMs applied to the individual parental employment histories. We found an increased risk of GCTs in the offspring of mothers occupationally exposed to high/very high social contact from child's conception to birth, especially among yolk sac tumors (OR=3.50; 95% CI=1.65, 7.43); this association persisted when examining maternal occupational exposure from birth to diagnosis (OR=2.77; 95% CI=1.29, 5.57). We also observed an elevated risk of all GCTs in the offspring of mothers who worked in the textile, clothing, and leather industry from birth to diagnosis (OR=2.19; 95% CI=1.09, 4.40). Paternal employment in the agriculture, forestry, and fishing industry from child's birth to diagnosis was associated with an increased risk of teratomas in offspring (OR=2.73; 95% CI=1.14, 6.78).