Current practices in the spatial analysis of cancer: flies in the ointment

While many lessons have been learned from the spatial analysis of cancer, there are several caveats that apply to many, if not all such analyses. As "flies in the ointment", these can substantially detract from a spatial analysis, and if not accounted for, can lead to weakened and erroneous conclusions. This paper discusses several assumptions and limitations of spatial analysis, identifies problems of scientific inference, and concludes with potential solutions and future directions

Local clustering in breast, lung and colorectal cancer in Long Island, New York

BACKGROUND: Analyses of spatial disease patterns usually employ a univariate approach that uses one technique to identify disease clusters. Because different methods are sensitive to different aspects of spatial pattern, an approach employing a battery of techniques is expected to describe geographic variation in human health more fully. This two-part study employs a multi-method approach to elucidate geographic variation in cancer incidence in Long Island, New York, and to evaluate spatial association with air-borne toxics. This first paper uses the local Moran statistic to identify cancer hotspots and spatial outliers. We evaluated the geographic distributions of breast cancer in females and colorectal and lung cancer in males and females in Nassau, Queens, and Suffolk counties, New York, USA. We calculated standardized morbidity ratios (SMR values) from New York State Department of Health (NYSDOH) data. RESULTS: We identified significant local clusters of high and low SMR and significant spatial outliers for each cancer-gender combination. We then compared our results with the study conducted by NYSDOH using Kulldorff's spatial scan statistic. We identified patterns on a smaller spatial scale with different cluster shapes than the NYSDOH analysis did, a consequence of different statistical methods and analysis scale. CONCLUSION: This is a methodological and comparative study to evaluate whether there is substantial benefit added by using a variety of techniques for geographic pattern detection at different spatial scales. We located significant spatial pattern in cancer morbidity in Nassau, Queens, and Suffolk counties. These results broadly agree with the results of other studies that used different techniques, but differ in specifics. The differences in our results and that of the NYSDOH underscore the need for an exploratory, integrative, and multi-scalar approach to assessing geographic patterns of disease, as different methods identify different patterns. We recommend that future studies of geographic patterns use a concordance of evidence from a multiscalar integrative geographic approach to assure that 1) different aspects of spatial pattern are fully identified and 2) the results from the suite of analyses are logically consistent

Geographic boundaries in breast, lung and colorectal cancers in relation to exposure to air toxics in Long Island, New York

BACKGROUND: This two-part study employs several statistical techniques to evaluate the geographic distribution of breast cancer in females and colorectal and lung cancers in males and females in Nassau, Queens, and Suffolk counties, New York, USA. In this second paper, we compare patterns in standardized morbidity ratios (SMR values), calculated from New York State Department of Health (NYSDOH) data, to geographic patterns in overall predicted risk (OPR) from air toxics using exposures estimated in the USEPA National Air Toxics Assessment database. RESULTS: We identified significant geographic boundaries in SMR and OPR. We found little or no association between the SMR of colorectal and breast cancers and the OPR for each cancer from exposure to the air toxics. We did find boundaries in male and female lung cancer SMR and boundaries in lung cancer OPR to be closer to one another than expected. CONCLUSION: While consistent with a causal relationship between air toxics and lung cancer incidence, the boundary analysis does not demonstrate the existence of a causal relationship. However, now that the areas of overlap between boundaries in lung cancer incidence and potential airborne exposures have been identified, we can begin to evaluate local- as well as large-scale determinants of lung cancer

In search of induction and latency periods: Space-time interaction accounting for residential mobility, risk factors and covariates

<p>Abstract</p> <p>Background</p> <p>Space-time interaction arises when nearby cases occur at about the same time, and may be attributable to an infectious etiology or from exposures that cause a geographically localized increase in risk. But available techniques for detecting interaction do not account for residential mobility, nor do they evaluate sensitivity to induction and latency periods. This is an important problem for cancer, where latencies of a decade or more occur.</p> <p>Methods</p> <p>New case-only clustering techniques are developed that account for residential mobility, latency and induction periods, relevant covariates (such as age) and risk factors (such as smoking). The statistical behavior of the methods is evaluated using simulated data to assess type I error (false positives) and statistical power. These methods are applied to 374 cases from an ongoing study of bladder cancer in 11 counties in southeastern Michigan, and the ability of the methods to localize space-time interaction at the individual-level is demonstrated.</p> <p>Results</p> <p>Significant interaction is found for induction periods of ~5 years and latency ~19.5 years. Data are still being collected and the observed clusters may be attributable to differential sampling in the study area.</p> <p>Conclusion</p> <p>Residential histories are increasingly available, raising the possibility of routine surveillance in a manner that accounts for individual mobility and that incorporates models of cancer latency and induction. These new techniques provide a mechanism for identifying those geographic locations and times associated with increases in cancer risk <it>above and beyond </it>that expected given covariates and risk factors in geographically mobile populations.</p

New Data and Tools for Integrating Discrete and Continuous Population Modeling Strategies

Realistic population models have interactions between individuals. Such interactions cause populations to behave as systems with nonlinear dynamics. Much population data analysis is done using linear models assuming no interactions between individuals. Such analyses miss strong influences on population behavior and can lead to serious errors—especially for infectious diseases. To promote more effective population system analyses, we present a flexible and intuitive modeling framework for infection transmission systems. This framework will help population scientists gain insight into population dynamics, develop theory about population processes, better analyze and interpret population data, design more powerful and informative studies, and better inform policy decisions. Our framework uses a hierarchy of infection transmission system models. Four levels are presented here: deterministic compartmental models using ordinary differential equations (DE); stochastic compartmental (SC) models that relax assumptions about population size and include stochastic effects; individual event history models (IEH) that relax the SC compartmental structure assumptions by allowing each individual to be unique. IEH models also track each individual's history, and thus, allow the simulation of field studies. Finally, dynamic network (DNW) models relax the assumption of the previous models that contacts between individuals are instantaneous events that do not affect subsequent contacts. Eventually it should be possible to transit between these model forms at the click of a mouse. An example is presented dealing with Cryptosporidium . It illustrates how transiting model forms helps assess water contamination effects, evaluate control options, and design studies of infection transmission systems using nucleotide sequences of infectious agents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75616/1/j.1749-6632.2001.tb02756.x.pd

Local indicators of geocoding accuracy (LIGA): theory and application

BACKGROUND: Although sources of positional error in geographic locations (e.g. geocoding error) used for describing and modeling spatial patterns are widely acknowledged, research on how such error impacts the statistical results has been limited. In this paper we explore techniques for quantifying the perturbability of spatial weights to different specifications of positional error. RESULTS: We find that a family of curves describes the relationship between perturbability and positional error, and use these curves to evaluate sensitivity of alternative spatial weight specifications to positional error both globally (when all locations are considered simultaneously) and locally (to identify those locations that would benefit most from increased geocoding accuracy). We evaluate the approach in simulation studies, and demonstrate it using a case-control study of bladder cancer in south-eastern Michigan. CONCLUSION: Three results are significant. First, the shape of the probability distributions of positional error (e.g. circular, elliptical, cross) has little impact on the perturbability of spatial weights, which instead depends on the mean positional error. Second, our methodology allows researchers to evaluate the sensitivity of spatial statistics to positional accuracy for specific geographies. This has substantial practical implications since it makes possible routine sensitivity analysis of spatial statistics to positional error arising in geocoded street addresses, global positioning systems, LIDAR and other geographic data. Third, those locations with high perturbability (most sensitive to positional error) and high leverage (that contribute the most to the spatial weight being considered) will benefit the most from increased positional accuracy. These are rapidly identified using a new visualization tool we call the LIGA scatterplot. Herein lies a paradox for spatial analysis: For a given level of positional error increasing sample density to more accurately follow the underlying population distribution increases perturbability and introduces error into the spatial weights matrix. In some studies positional error may not impact the statistical results, and in others it might invalidate the results. We therefore must understand the relationships between positional accuracy and the perturbability of the spatial weights in order to have confidence in a study's results

Visualization and exploratory analysis of epidemiologic data using a novel space time information system

Abstract Background Recent years have seen an expansion in the use of Geographic Information Systems (GIS) in environmental health research. In this field GIS can be used to detect disease clustering, to analyze access to hospital emergency care, to predict environmental outbreaks, and to estimate exposure to toxic compounds. Despite these advances the inability of GIS to properly handle temporal information is increasingly recognised as a significant constraint. The effective representation and visualization of both spatial and temporal dimensions therefore is expected to significantly enhance our ability to undertake environmental health research using time-referenced geospatial data. Especially for diseases with long latency periods (such as cancer) the ability to represent, quantify and model individual exposure through time is a critical component of risk estimation. In response to this need a STIS – a Space Time Information System has been developed to visualize and analyze objects simultaneously through space and time. Results In this paper we present a "first use" of a STIS in a case-control study of the relationship between arsenic exposure and bladder cancer in south eastern Michigan. Individual arsenic exposure is reconstructed by incorporating spatiotemporal data including residential mobility and drinking water habits. The unique contribution of the STIS is its ability to visualize and analyze residential histories over different temporal scales. Participant information is viewed and statistically analyzed using dynamic views in which values of an attribute change through time. These views include tables, graphs (such as histograms and scatterplots), and maps. In addition, these views can be linked and synchronized for complex data exploration using cartographic brushing, statistical brushing, and animation. Conclusion The STIS provides new and powerful ways to visualize and analyze how individual exposure and associated environmental variables change through time. We expect to see innovative space-time methods being utilized in future environmental health research now that the successful "first use" of a STIS in exposure reconstruction has been accomplished.http://deepblue.lib.umich.edu/bitstream/2027.42/112824/1/12942_2004_Article_41.pd

Case-control geographic clustering for residential histories accounting for risk factors and covariates

BACKGROUND: Methods for analyzing space-time variation in risk in case-control studies typically ignore residential mobility. We develop an approach for analyzing case-control data for mobile individuals and apply it to study bladder cancer in 11 counties in southeastern Michigan. At this time data collection is incomplete and no inferences should be drawn – we analyze these data to demonstrate the novel methods. Global, local and focused clustering of residential histories for 219 cases and 437 controls is quantified using time-dependent nearest neighbor relationships. Business address histories for 268 industries that release known or suspected bladder cancer carcinogens are analyzed. A logistic model accounting for smoking, gender, age, race and education specifies the probability of being a case, and is incorporated into the cluster randomization procedures. Sensitivity of clustering to definition of the proximity metric is assessed for 1 to 75 k nearest neighbors. RESULTS: Global clustering is partly explained by the covariates but remains statistically significant at 12 of the 14 levels of k considered. After accounting for the covariates 26 Local clusters are found in Lapeer, Ingham, Oakland and Jackson counties, with the clusters in Ingham and Oakland counties appearing in 1950 and persisting to the present. Statistically significant focused clusters are found about the business address histories of 22 industries located in Oakland (19 clusters), Ingham (2) and Jackson (1) counties. Clusters in central and southeastern Oakland County appear in the 1930's and persist to the present day. CONCLUSION: These methods provide a systematic approach for evaluating a series of increasingly realistic alternative hypotheses regarding the sources of excess risk. So long as selection of cases and controls is population-based and not geographically biased, these tools can provide insights into geographic risk factors that were not specifically assessed in the case-control study design

Improving exposure assessment in environmental epidemiology: Application of spatio-temporal visualization tools

A thorough assessment of human exposure to environmental agents should incorporate mobility patterns and temporal changes in human behaviors and concentrations of contaminants; yet the temporal dimension is often under-emphasized in exposure assessment endeavors, due in part to insufficient tools for visualizing and examining temporal datasets. Spatio-temporal visualization tools are valuable for integrating a temporal component, thus allowing for examination of continuous exposure histories in environmental epidemiologic investigations. An application of these tools to a bladder cancer case-control study in Michigan illustrates continuous exposure life-lines and maps that display smooth, continuous changes over time. Preliminary results suggest increased risk of bladder cancer from combined exposure to arsenic in drinking water (>25 μ g/day) and heavy smoking (>30 cigarettes/day) in the 1970s and 1980s, and a possible cancer cluster around automotive, paint, and organic chemical industries in the early 1970s. These tools have broad application for examining spatially- and temporally-specific relationships between exposures to environmental risk factors and disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47931/1/10109_2005_Article_149.pd