Heather E. Danysh

Traffic-related air pollution and the incidence of childhood central nervous system tumors: Texas, 2001–2009

Due to increasing concerns regarding air pollution and childhood cancer, we conducted a population‐based study evaluating the association between traffic‐related hazardous air pollutants (1,3‐butadiene, benzene, diesel particulate matter [DPM]) and the incidence of childhood central nervous system (CNS) tumors.

Association of traffic-related hazardous air pollutants and cervical dysplasia in an urban multiethnic population: a cross-sectional study

BackgroundHuman papillomavirus (HPV) infection is a necessary cause in the development of cervical cancer; however, not all women infected with HPV develop cervical cancer indicating that other risk factors are involved. Our objective was to determine the association between exposure to ambient levels of common traffic-related air toxics and cervical dysplasia, a precursor lesion for cervical cancer.MethodsThe study sample consisted of women enrolled in a Phase II clinical trial to evaluate diagnostic techniques for cervical disease in Houston, Texas. The current assessment is a secondary data analysis in which cases were defined as women diagnosed with cervical dysplasia, while those without cervical dysplasia served as controls. Residential census tract-level estimates of ambient benzene, diesel particulate matter (DPM), and polycyclic aromatic hydrocarbons (PAHs) were used to assess exposure. Census tract-level pollutant estimates were obtained from the United States Environmental Protection Agency. Multivariable logistic regression was used to estimate prevalence odds ratios (aOR) and 95% confidence intervals (CI) adjusted for age, race/ethnicity, education, smoking status, and HPV status.ResultsWomen in the highest residential exposure categories for benzene and DPM had an increased prevalence of cervical dysplasia compared to the lowest exposure category (Benzene: aOR [95% CI] for high exposure = 1.97[1.07-3.62], very high exposure = 2.30[1.19-4.46]. DPM: aOR [95% CI] for high exposure = 2.83[1.55-5.16], very high exposure = 2.10[1.07-4.11]). Similarly, women with high residential exposure to PAHs had an increased prevalence of cervical dysplasia (aOR [95% CI] = 2.46[1.35-4.48]). The highest PAH exposure category was also positively associated with cervical dysplasia prevalence but was not statistically significant. Assessment of the combined effect of HAP exposure indicates that exposure to high levels of more than one HAP is positively associated with cervical dysplasia prevalence (p for trend = 0.004).ConclusionsTraffic-related HAPs, such as benzene, DPM, and PAHs, are not as well-regulated and monitored as criteria air pollutants (e.g., ozone), underscoring the need for studies evaluating the role of these toxicants on disease risk. Our results suggest that exposure to traffic-related air toxics may increase cervical dysplasia prevalence.

Maternal residential proximity to major roadways at delivery and childhood central nervous system tumors.

BACKGROUND Due to concerns over the impact of traffic-related air pollution on childhood cancers, we evaluated the association between residential proximity to major roadways and childhood central nervous system (CNS) tumors. METHODS The Texas Cancer Registry provided information on children diagnosed with a CNS tumor at <5 years of age and born in Texas for the period 2003-2009 (n=315). Birth certificate controls were frequency matched to cases (5:1) on birth year (n=1575). We assigned exposures to traffic-related air pollution using residential proximity to major roadways based on the maternal residence at the time of delivery. Logistic regression was used to generate unadjusted and adjusted odds ratios and 95% confidence intervals (CI). We evaluated CNS tumors as a group and by histologic type. RESULTS Maternal residential proximity to major roadways at delivery was positively associated with the odds of offspring having a CNS tumor. Specifically, for every kilometer closer to a major roadway, the odds of offspring having a CNS tumor increased by 30% (95% CI: 1.0, 1.7). Mothers living ≤500 meters (m) from a major roadway were 31% (95% CI: 1.0, 1.8) more likely to have offspring with any CNS tumor and 3.1-times (95% CI: 0.9, 10.4) more likely to have offspring with an ependymoma compared to mothers living >500m from the nearest major roadway. Moreover, compared to mothers living in areas with low roadway density, those living in areas with high roadway density were 51% (95% CI: 1.1, 2.1) more likely to have offspring with any CNS tumor and 4.2-times (95% CI: 1.2, 14.9) more likely to have offspring with an ependymoma. There were no statistically significant associations observed between continuous distance to major roadways and ependymoma as well as between the proximity measures and the other evaluated CNS tumor phenotypic groups. CONCLUSIONS The results of this large population-based study indicate that mothers who live near major roadways or in areas with high roadway density may be more likely to have offspring with a CNS tumor, particularly an ependymoma.

Air toxics and birth defects: a Bayesian hierarchical approach to evaluate multiple pollutants and spina bifida

BackgroundWhile there is evidence that maternal exposure to benzene is associated with spina bifida in offspring, to our knowledge there have been no assessments to evaluate the role of multiple hazardous air pollutants (HAPs) simultaneously on the risk of this relatively common birth defect. In the current study, we evaluated the association between maternal exposure to HAPs identified by the United States Environmental Protection Agency (U.S. EPA) and spina bifida in offspring using hierarchical Bayesian modeling that includes Stochastic Search Variable Selection (SSVS).MethodsThe Texas Birth Defects Registry provided data on spina bifida cases delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual HAP levels were obtained from the U.S. EPA’s 1999 Assessment System for Population Exposure Nationwide. Using the distribution among controls, exposure was categorized as high exposure (>95th percentile), medium exposure (5th-95th percentile), and low exposure (<5th percentile, reference). We used hierarchical Bayesian logistic regression models with SSVS to evaluate the association between HAPs and spina bifida by computing an odds ratio (OR) for each HAP using the posterior mean, and a 95% credible interval (CI) using the 2.5th and 97.5th quantiles of the posterior samples. Based on previous assessments, any pollutant with a Bayes factor greater than 1 was selected for inclusion in a final model.ResultsTwenty-five HAPs were selected in the final analysis to represent “bins” of highly correlated HAPs (ρ > 0.80). We identified two out of 25 HAPs with a Bayes factor greater than 1: quinoline (ORhigh = 2.06, 95% CI: 1.11-3.87, Bayes factor = 1.01) and trichloroethylene (ORmedium = 2.00, 95% CI: 1.14-3.61, Bayes factor = 3.79).ConclusionsOverall there is evidence that quinoline and trichloroethylene may be significant contributors to the risk of spina bifida. Additionally, the use of Bayesian hierarchical models with SSVS is an alternative approach in the evaluation of multiple environmental pollutants on disease risk. This approach can be easily extended to environmental exposures, where novel approaches are needed in the context of multi-pollutant modeling.

Family history of cancer and childhood rhabdomyosarcoma: a report from the Children's Oncology Group and the Utah Population Database

Relatively little is known about the epidemiology and factors underlying susceptibility to childhood rhabdomyosarcoma (RMS). To better characterize genetic susceptibility to childhood RMS, we evaluated the role of family history of cancer using data from the largest case–control study of RMS and the Utah Population Database (UPDB). RMS cases (n = 322) were obtained from the Childrens Oncology Group (COG). Population‐based controls (n = 322) were pair‐matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate the association between family history of cancer and childhood RMS. The results were validated using the UPDB, from which 130 RMS cases were identified and matched to controls (n = 1300) on sex and year of birth. The results were combined to generate summary odds ratios (ORs) and 95% confidence intervals (CI). Having a first‐degree relative with a cancer history was more common in RMS cases than controls (ORs = 1.39, 95% CI: 0.97–1.98). Notably, this association was stronger among those with embryonal RMS (ORs = 2.44, 95% CI: 1.54–3.86). Moreover, having a first‐degree relative who was younger at diagnosis of cancer (<30 years) was associated with a greater risk of RMS (ORs = 2.37, 95% CI: 1.34–4.18). In the largest analysis of its kind, we found that most children diagnosed with RMS did not have a family history of cancer. However, our results indicate an increased risk of RMS (particularly embryonal RMS) in children who have a first‐degree relative with cancer, and among those whose relatives were diagnosed with cancer at <30 years of age.

Neighborhood-Based Socioeconomic Position and Risk of Oral Clefts Among Offspring.

OBJECTIVES We determined the association between maternal neighborhood socioeconomic position (SEP) and the risk of cleft lip with or without cleft palate (CL±P) or cleft palate alone (CP) in offspring. METHODS We obtained information on CL±P (n = 2555) and CP (n = 1112) cases and unaffected controls (n = 14 735) among infants delivered during 1999 to 2008 from the Texas Birth Defects Registry. Neighborhood SEP variables, drawn from the 2000 US Census, included census tract-level poverty, education, unemployment, occupation, housing, and crowding, from which we created a composite neighborhood deprivation index (NDI). We used mixed-effects logistic regression to evaluate neighborhood SEP and oral clefts. RESULTS Mothers with CL±P-affected offspring were more likely to live in high-NDI (adverse) areas than mothers with unaffected offspring (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.05, 1.37). This association was strongest among Hispanic mothers (OR = 1.32, 95% CI = 1.07, 1.62). No associations were observed with CP. CONCLUSIONS Using data from one of the worlds largest active surveillance birth defects registries, we found that adverse neighborhood SEP is modestly associated with CL±P, especially among Hispanics. These findings may have important implications for health disparities prevention.

Mapping the Epidemiology of Kaposi Sarcoma and Non-Hodgkin Lymphoma Among Children in Sub-Saharan Africa: A Review

Children with human immunodeficiency virus (HIV) have an increased risk of developing Kaposi Sarcoma (KS) and non‐Hodgkin lymphoma (NHL) compared to HIV‐negative children. We compiled currently published epidemiologic data on KS and NHL among children in sub‐Saharan Africa (SSA). Among countries with available data, the median incidence of KS was 2.05/100,000 in the general pediatric population and 67.35/100,000 among HIV‐infected children. The median incidence of NHL was 1.98/100,000 among the general pediatric population, while data on NHL incidence among HIV‐infected children were lacking. Larger regional studies are needed to better address the dearth of epidemiologic information on pediatric KS and NHL in SSA.

Residential Radon Exposure and Incidence of Childhood Lymphoma in Texas, 1995-2011.

There is warranted interest in assessing the association between residential radon exposure and the risk of childhood cancer. We sought to evaluate the association between residential radon exposure and the incidence of childhood lymphoma in Texas. The Texas Cancer Registry (n = 2147) provided case information for the period 1995–2011. Denominator data were obtained from the United States Census. Regional arithmetic mean radon concentrations were obtained from the Texas Indoor Radon Survey and linked to residence at diagnosis. Exposure was assessed categorically: ≤25th percentile (reference), >25th to ≤50th percentile, >50th to ≤75th percentile, and >75th percentile. Negative binomial regression generated adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI). We evaluated lymphoma overall and by subtype: Hodgkin (HL; n = 1248), Non-Hodgkin excluding Burkitt (non-BL NHL; n = 658), Burkitt (BL; n = 241), and Diffuse Large B-cell (DLBCL; n = 315). There was no evidence that residential radon exposure was positively associated with lymphoma overall, HL, or BL. Areas with radon concentrations >75th percentile had a marginal increase in DLBCL incidence (aIRR = 1.73, 95% CI: 1.03–2.91). In one of the largest studies of residential radon exposure and the incidence of childhood lymphoma, we found little evidence to suggest a positive or negative association; an observation consistent with previous studies.

Differences in environmental exposure assignment due to residential mobility among children with a central nervous system tumor: Texas, 1995-2009.

In epidemiologic studies of childhood cancer, environmental exposures are often assigned based on either residence at birth or diagnosis without considering the impact of residential mobility. Therefore, we evaluated residential mobility and exposure assignment differences to hazardous air pollutants between birth and diagnosis in children with a central nervous system (CNS) tumor. Children diagnosed with CNS tumors during 1995–2009 (N=1,196) were identified from the Texas Cancer Registry. Census tract-level estimates of 1,3-butadiene and benzene were used to assign quartiles of exposure based on the maternal residence at birth and the child’s residence at diagnosis. Overall, 64% of younger (0–4 years) children and 79% of older (5–14 years) children moved between birth and diagnosis. Using mixed-effects ordinal logistic regression, residence at diagnosis compared to birth did not result in a significant change in exposure assignment for younger children; however, older children were more likely to be placed in a lower 1,3-butadiene or benzene exposure quartile based on residence at diagnosis compared to birth (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.45–0.76; OR=0.57, 95% CI=0.44–0.75, respectively). In conclusion, while the majority of children moved between birth and CNS tumor diagnosis, mobility did not significantly impact 1,3-butadiene and benzene exposure assessment in younger children.

The Role of Childhood Infections and Immunizations on Childhood Rhabdomyosarcoma: A Report From the Children's Oncology Group

Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy.