Spatial-temporal analysis of breast cancer in upper Cape Cod, Massachusetts

INTRODUCTION. The reasons for elevated breast cancer rates in the upper Cape Cod area of Massachusetts remain unknown despite several epidemiological studies that investigated possible environmental risk factors. Data from two of these population-based case-control studies provide geocoded residential histories and information on confounders, creating an invaluable dataset for spatial-temporal analysis of participants' residency over five decades. METHODS. The combination of statistical modeling and mapping is a powerful tool for visualizing disease risk in a spatial-temporal analysis. Advances in geographic information systems (GIS) enable spatial analytic techniques in public health studies previously not feasible. Generalized additive models (GAMs) are an effective approach for modeling spatial and temporal distributions of data, combining a number of desirable features including smoothing of geographical location, residency duration, or calendar years; the ability to estimate odds ratios (ORs) while adjusting for confounders; selection of optimum degree of smoothing (span size); hypothesis testing; and use of standard software. We conducted a spatial-temporal analysis of breast cancer case-control data using GAMs and GIS to determine the association between participants' residential history during 1947–1993 and the risk of breast cancer diagnosis during 1983–1993. We considered geographic location alone in a two-dimensional space-only analysis. Calendar year, represented by the earliest year a participant lived in the study area, and residency duration in the study area were modeled individually in one-dimensional time-only analyses, and together in a two-dimensional time-only analysis. We also analyzed space and time together by applying a two-dimensional GAM for location to datasets of overlapping calendar years. The resulting series of maps created a movie which allowed us to visualize changes in magnitude, geographic size, and location of elevated breast cancer risk for the 40 years of residential history that was smoothed over space and time. RESULTS. The space-only analysis showed statistically significant increased areas of breast cancer risk in the northern part of upper Cape Cod and decreased areas of breast cancer risk in the southern part (p-value = 0.04; ORs: 0.90–1.40). There was also a significant association between breast cancer risk and calendar year (p-value = 0.05; ORs: 0.53–1.38), with earlier calendar years resulting in higher risk. The results of the one-dimensional analysis of residency duration and the two-dimensional analysis of calendar year and duration showed that the risk of breast cancer increased with increasing residency duration, but results were not statistically significant. When we considered space and time together, the maps showed a large area of statistically significant elevated risk for breast cancer near the Massachusetts Military Reservation (p-value range:0.02–0.05; ORs range: 0.25–2.5). This increased risk began with residences in the late 1940s and remained consistent in size and location through the late 1950s. CONCLUSION. Spatial-temporal analysis of the breast cancer data may help identify new exposure hypotheses that warrant future epidemiologic investigations with detailed exposure models. Our methods allow us to visualize breast cancer risk, adjust for known confounders including age at diagnosis or index year, family history of breast cancer, parity and age at first live- or stillbirth, and test for the statistical significance of location and time. Despite the advantages of GAMs, analyses are for exploratory purposes and there are still methodological issues that warrant further research. This paper illustrates that GAM methods are a suitable alternative to widely-used cluster detection methods and may be preferable when residential histories from existing epidemiological studies are available.National Cancer Institute (5R03CA119703-02); National Institute of Enviornmental Health (5P42ES007381

Prenatal Exposure to Tetrachloroethylene-Contaminated Drinking Water and the Risk of Congenital Anomalies: A Retrospective Cohort Study

BACKGROUND: Prior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring. OBJECTIVES: This retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception. METHODS: The study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model. RESULTS: Children whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure. CONCLUSION: The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.National Institute of Environmental Health (5 P42 ES007381); National Institutes of Healt

Alcohol Outlets and Violent Crime in Washington D.C.

Objective: Alcohol is more likely than any other drug to be involved in substance-related violence. In 2000 violence-related and self-directed injuries accounted for an estimated $37 billion and$33 billion in productivity losses and medical treatment, respectively. A review of emergency department data revealed violence and clinically identified trauma-related injuries have the strongest correlation among alcohol-dependent injuries. At the environmental level there is a relationship between alcohol outlet density and violent crime. A limited number of studies have examined the relationship between alcohol outlet type and the components of violent crime. The aim of this study is to examine the relationship between the aggregate components of violent crime and alcohol outlet density by type of outlet.Methods: For this study we used Washington, D.C. census tract data from the 2000 census to examine neighborhood characteristics. Alcohol outlet, violent crime, and population-level data for Washington, D.C. were drawn from various official yet publicly available sources. We developed an analytic database to examine the relationship between alcohol outlet category and four types of violent crime. After estimating spatial correlation and determining spatial dependence, we used a negative binomial regression analysis to assess the alcohol availability-violent crime association, while controlling for structural correlates of violence.Results: Independent of alternative structural correlates of violent crime, including the prevalence of weapons and illicit drugs, community-level alcohol outlet density is significantly associated with assaultive violence. Outlets were significantly related to robbery, assault, and sexual offenses. In addition, the relationship among on-premise and off-premise outlets varied across violent crime categories.Conclusion: In Washington, D.C., alcohol outlet density is significantly associated with the violent crimes. The science regarding alcohol outlet density and alcohol-related harms has clearly identified the use of limiting outlet density to reduce the associated adverse health consequences. Moreover, the disproportionate burden among poor urban and minority communities underscores the urgency to develop context-appropriate policies to regulate the functioning of current alcohol outlet establishments and to prevent the proliferation of future outlets. [West J Emerg Med. 2010; 11(3): 284-291.

A power comparison of generalized additive models and the spatial scan statistic in a case-control setting

<p>Abstract</p> <p>Background</p> <p>A common, important problem in spatial epidemiology is measuring and identifying variation in disease risk across a study region. In application of statistical methods, the problem has two parts. First, spatial variation in risk must be detected across the study region and, second, areas of increased or decreased risk must be correctly identified. The location of such areas may give clues to environmental sources of exposure and disease etiology. One statistical method applicable in spatial epidemiologic settings is a generalized additive model (GAM) which can be applied with a bivariate LOESS smoother to account for geographic location as a possible predictor of disease status. A natural hypothesis when applying this method is whether residential location of subjects is associated with the outcome, i.e. is the smoothing term necessary? Permutation tests are a reasonable hypothesis testing method and provide adequate power under a simple alternative hypothesis. These tests have yet to be compared to other spatial statistics.</p> <p>Results</p> <p>This research uses simulated point data generated under three alternative hypotheses to evaluate the properties of the permutation methods and compare them to the popular spatial scan statistic in a case-control setting. Case 1 was a single circular cluster centered in a circular study region. The spatial scan statistic had the highest power though the GAM method estimates did not fall far behind. Case 2 was a single point source located at the center of a circular cluster and Case 3 was a line source at the center of the horizontal axis of a square study region. Each had linearly decreasing logodds with distance from the point. The GAM methods outperformed the scan statistic in Cases 2 and 3. Comparing sensitivity, measured as the proportion of the exposure source correctly identified as high or low risk, the GAM methods outperformed the scan statistic in all three Cases.</p> <p>Conclusions</p> <p>The GAM permutation testing methods provide a regression-based alternative to the spatial scan statistic. Across all hypotheses examined in this research, the GAM methods had competing or greater power estimates and sensitivities exceeding that of the spatial scan statistic.</p

A multilevel non-hierarchical study of birth weight and socioeconomic status

<p>Abstract</p> <p>Background</p> <p>It is unclear whether the socioeconomic status (SES) of the community of residence has a substantial association with infant birth weight. We used multilevel models to examine associations of birth weight with family- and community-level SES in the Cape Cod Family Health Study. Data were collected retrospectively on births to women between 1969 and 1983 living on Cape Cod, Massachusetts. The sample included siblings born in different residences with differing community-level SES.</p> <p>Methods</p> <p>We used cross-classified models to account for multiple levels of correlation in a non-hierarchical data structure. We accounted for clustering at family- and community-levels. Models included extensive individual- and family-level covariates. SES variables of interest were maternal education; paternal occupation; percent adults living in poverty; percent adults with a four year college degree; community mean family income; and percent adult unemployment.</p> <p>Results</p> <p>Residual correlation was detected at the family- but not the community-level. Substantial effects sizes were observed for family-level SES while smaller magnitudes were observed for community-level SES. Overall, higher SES corresponded to increased birth weight though neither family- nor community-level variables had significant associations with the outcome. In a model applied to a reduced sample that included a single child per family, enforcing a hierarchical data structure, paternal occupation was found to have a significant association with birth weight (p = 0.033). Larger effect sizes for community SES appeared in models applied to the full sample that contained limited covariates, such as those typically found on birth certificates.</p> <p>Conclusions</p> <p>Cross-classified models allowed us to include more than one child per family even when families moved between births. There was evidence of mild associations between family SES and birth weight. Stronger associations between paternal occupation and birth weight were observed in models applied to reduced samples with hierarchical data structures, illustrating consequences of excluding observations from the cross-classified analysis. Models with limited covariates showed associations of birth weight with community SES. In models adjusting for a complete set of individual- and family-level covariates, community SES was not as important.</p

Exposure to Polyfluoroalkyl Chemicals and Attention Deficit/Hyperactivity Disorder in U.S. Children 12–15 Years of Age

Background: Polyfluoroalkyl chemicals (PFCs) have been widely used in consumer products. Exposures in the United States and in world populations are widespread. PFC exposures have been linked to various health impacts, and data in animals suggest that PFCs may be potential developmental neurotoxicants. Objectives: We evaluated the associations between exposures to four PFCs and parental report of diagnosis of attention deficit/hyperactivity disorder (ADHD). Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 and 2003–2004 for children 12–15 years of age. Parental report of a previous diagnosis by a doctor or health care professional of ADHD in the child was the primary outcome measure. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) levels were measured in serum samples from each child. Results: Parents reported that 48 of 571 children included in the analysis had been diagnosed with ADHD. The adjusted odds ratio (OR) for parentally reported ADHD in association with a 1-μg/L increase in serum PFOS (modeled as a continuous predictor) was 1.03 [95% confidence interval (CI), 1.01–1.05]. Adjusted ORs for 1-μg/L increases in PFOA and PFHxS were also statistically significant (PFOA: OR = 1.12; 95% CI, 1.01–1.23; PFHxS: OR = 1.06; 95% CI, 1.02–1.11), and we observed a nonsignificant positive association with PFNA (OR = 1.32; 95% CI, 0.86–2.02). Conclusions: Our results, using cross-sectional data, are consistent with increased odds of ADHD in children with higher serum PFC levels. Given the extremely prevalent exposure to PFCs, follow-up of these data with cohort studies is needed