Annual Review of Public Health - Volume 31, 2010

Genomic and genetic information is rapidly becoming a major element in public health research and emerging public health practice. This symposium reviews the methods, findings, and significance of genome-wide association studies from epidemiological and statistical points of view. We examine infectious and inflammatory components of gene-environment interaction in the respiratory system. We note the need for nutrient and dietary data and many other kinds of environmental exposure data in population-based genomic studies. Then we explore the sufficiency of a well-informed family history for public health and family counseling purposes. Finally, in an era of direct-to-consumer genomic test promotion, we review the evidence on the critical question, will genetic risk profiles motivate individuals and families to choose more healthful behaviors? This symposium builds on the foundation of the symposium on Public Health Genetics in Volume 21 (2000) of the Annual Review of Public Health.

Genome-wide association studies (GWAS) provide an important avenue for undertaking an agnostic evaluation of the association between common genetic variants and risk of disease. Recent advances in our understanding of human genetic variation and the technology to measure such variation have made GWAS feasible. Over the past few years a multitude of GWAS have identified and replicated many associated variants. These findings are enriching our knowledge about the genetic basis of disease and leading some to advocate using GWA study results for genetic testing. For many of the GWA study results, however, the underlying mechanisms remain unclear and the findings explain only a limited amount of heritability. These issues may be clarified by more detailed investigations, including analyses of less common variants, sequence-level data, and environmental exposures. Such studies should help clarify the potential value of genetic testing to the public's health.

Despite the considerable enthusiasm about the yield of novel and replicated discoveries of genetic associations from the new generation of genome-wide association studies (GWAS), the proportion of the heritability of most complex diseases that have been studied to date remains small. Some of this “dark matter” could be due to gene-environment (G × E) interactions or more complex pathways involving multiple genes and exposures. We review the basic epidemiologic study design and statistical analysis approaches to studying G × E interactions individually and then consider more comprehensive approaches to studying entire pathways or GWAS data. In addition to the usual issues in genetic association studies, particular care is needed in exposure assessment, and very large sample sizes are required. Although hypothesis-driven, pathway-based and agnostic GWA study approaches are generally viewed as opposite poles, we suggest that the two can be usefully married using hierarchical modeling strategies that exploit external pathway knowledge in mining genome-wide data.

Gene-environment interactions are the indisputable cause of most respiratory diseases. However, we still have very limited understanding of the mechanisms that guide these interactions. Although the conceptual approaches to environmental genomics were established several decades ago, the tools are only now available to better define the mechanisms that underlie the interactions among these important etiological features of lung disease. In this article, we summarize recent insights in the environmental genomics (ecogenomics) of common nonmalignant respiratory diseases (asthma, COPD, pulmonary fibrosis, and respiratory infections), describe the framework of gene-environment interactions that inform the pathogenesis of respiratory diseases, and propose future research directions that will help translate scientific advances into public health gains.

All diseases have a genetic predisposition. Genome-wide association studies (GWASs) by large international consortia are discovering genetic variants that contribute to complex diseases. However, nutrient information is missing, which is essential for the development of dietary advice for prevention and management of disease. Nutrigenetics/nutrigenomics studies provide data on mechanisms of nutrient and gene interactions in health and disease needed for personalized nutrition. A process will be needed to define when gene-nutrient-disease associations are ready to be evaluated as potential tools to improve public health.

Family history is a risk factor for many chronic diseases, including cancer, cardiovascular disease, and diabetes. Professional guidelines usually include family history to assess health risk, initiate interventions, and motivate behavioral changes. The advantages of family history over other genomic tools include a lower cost, greater acceptability, and a reflection of shared genetic and environmental factors. However, the utility of family history in public health has been poorly explored. To establish family history as a public health tool, it needs to be evaluated within the ACCE framework (analytical validity; clinical validity; clinical utility; and ethical, legal, and social issues). Currently, private and public organizations are developing tools to collect standardized family histories of many diseases. Their goal is to create family history tools that have decision support capabilities and are compatible with electronic health records. These advances will help realize the potential of family history as a public health tool.

This report describes the use of information emerging from genetic discovery to motivate risk-reducing health behaviors. Most research to date has evaluated the effects of information related to rare genetic variants on screening behaviors, in which genetic risk feedback has been associated consistently with improved screening adherence. The limited research with common genetic variants suggests that genetic information, when based on single-gene variants with low-risk probabilities, has little impact on behavior. The effect on behavioral outcomes of more realistic testing scenarios in which genetic risk is based on numerous genetic variants is largely unexplored. Little attention has been directed to matching genetic information to the literacy levels of target audiences. Another promising area for research is consideration of using genetic information to identify risk shared within kinship networks and to expand the influence of behavior change beyond the individual.

Several key factors bear on the interpretation of prevention trials and observational studies that inform prevention strategies. These factors include the underlying disease process and aspects of the intervention: sustainability of behavior change, the time course of the intervention within the disease process, dose and duration of exposure needed to effect risk reduction, durability of the impact of intervention, and methodological problems in implementing and interpreting randomized trials and observational studies to evaluate prevention strategies. The question asked through an intent-to-treat analysis of a randomized controlled trial (RCT) differs from that in the observational setting. Furthermore, the long duration necessary to conduct prevention trials and the resulting lack of adherence to therapy can bias results toward the null. A broader range of approaches to evaluate prevention interventions and programs with improved knowledge synthesis and translation to public health practice will speed our progress toward achieving public health and prevention of chronic diseases.

The close of the twentieth century brought historic changes in cancer risk factors, early detection, and treatment. As a consequence, we have seen two decades of steadily declining risk of death from cancer in the United States. The reasons for declining cancer mortality rates are largely known: reduced tobacco use, the adoption of cancer early-detection methods, and better cancer therapeutics. Despite this progress, disparities in cancer mortality persist across different groups defined by race and social class. Because all the factors that account for declining cancer trends are influenced strongly by social class, and because of large social class disparities in cancer risk factors, there will likely be a widening gap in cancer mortality among those in lower socioeconomic groups in the future. This article reviews the trends in risk factors for cancer mortality and discusses the persistent problem of disparities by race and social class.

Benzene is a ubiquitous chemical in our environment that causes acute leukemia and probably other hematological cancers. Evidence for an association with childhood leukemia is growing. Exposure to benzene can lead to multiple alterations that contribute to the leukemogenic process, indicating a multimodal mechanism of action. Research is needed to elucidate the different roles of multiple metabolites in benzene toxicity and the pathways that lead to their formation. Studies to date have identified a number of polymorphisms in candidate genes that confer susceptibility to benzene hematotoxicity. However, a genome-wide study is needed to truly assess the role of genetic variation in susceptibility. Benzene affects the blood-forming system at low levels of occupational exposure, and there is no evidence of a threshold. There is probably no safe level of exposure to benzene, and all exposures constitute some risk in a linear, if not supralinear, and additive fashion.

Uncertainty in assessment of individual exposure levels leads to bias, often, but not always, toward the null in estimates of health effects, and to underestimation of the variability of the estimates, leading to anticonservative p-values. In the absence of data on the uncertainty in individual exposure estimates, sensitivity analysis, also known as uncertainty analysis and bias analysis, is available. Hypothesized values of key parameters of the model relating the observed exposure to the true exposure are used to assess the resulting amount of bias in point and interval estimates. In general, the relative risk estimates can vary from zero to infinity as the hypothesized values of key parameters of the measurement error model vary. Thus, we recommend that exposure validation data be used to empirically adjust point and interval estimates of health effects for measurement error. The remainder of this review gives an overview of available methods for doing so. Just as we routinely adjust for confounding, we can and should routinely adjust for measurement error.

The extensive flooding in the aftermath of Hurricanes Katrina and Rita created conditions ideal for indoor mold growth, raising concerns about the possible adverse health effects associated with indoor mold exposure. Studies evaluating the levels of indoor and outdoor molds in the months following the hurricanes found high levels of mold growth. Homes with greater flood damage, especially those with >3 feet of indoor flooding, demonstrated higher levels of mold growth compared with homes with little or no flooding. Water intrusion due to roof damage was also associated with mold growth. However, no increase in the occurrence of adverse health outcomes has been observed in published reports to date. This article considers reasons why studies of mold exposure after the hurricane do not show a greater health impact.

By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrine-disrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs—i.e., reduce, reuse, recycle, rethink, restrain—for minimizing pre- and postnatal exposures to potentially harmful components of plastics.

Unintentional injuries are the largest source of premature morbidity and mortality and the leading cause of death among adolescents 10–19 years of age. Fatal injury rates of males are twice those of females, and racial disparities in injury are pronounced. Transportation is the largest source of these injuries, principally as drivers and passengers, but also as cyclists and pedestrians. Other major causes involve drowning, poisonings, fires, sports and recreation, and work-related injuries. Implementing known and effective prevention strategies such as using seat belts and bicycle and motorcycle helmets, installing residential smoke alarms, reducing misuse of alcohol, strengthening graduated driver licensing laws, promoting policy change, using safety equipment in sports and leisure, and protecting adolescents at work will all contribute to reducing injuries. The frequency, severity, potential for death and disability, and costs of these injuries, together with the high success potential of prevention strategies, make injury prevention a key public health goal to improve adolescent health in the future.

Evaluability assessment, also commonly known as exploratory evaluation, has assisted the field of public health to improve programs and to develop a pragmatic, practice-based research agenda. Evaluability assessment was originally developed as a low-cost pre-evaluation activity to prepare better for conventional evaluations of programs, practices, and some policies. For public health programs, however, it serves several other important purposes: (a) giving program staff rapid, constructive feedback about program operations; (b) assisting the core public health planning and assurance functions by helping to develop realistic objectives and providing low-cost, rapid feedback on implementation; (c) navigating federal performance measurement requirements; (d) translating research into practice by examining the feasibility, acceptability, and adaptation of evidence-based practices in new settings and populations; and (e) translating practice into research by identifying promising new approaches to achieve public health goals.

Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause ∼70% of cervical cancers, and clinical trials have demonstrated 90%–100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This review summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated framework can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research.

The broad scope of the public health mission leads to an increasingly diverse workforce. Given the range of feeder disciplines and the reality that much of the workforce does not have formal training in public health science and practice, a pressing need exists for training and education throughout the workforce. Just as we in public health take a rigorous approach to our science, so too should we take a rigorous, evidence-driven approach to workforce development. In this review, we recommend a framework for workforce education in public health, integrating three critical conceptual approaches: (a) adult learning theory; (b) competency-based education; and (c) the expanded Dreyfus model in public health, an addition to the Dreyfus model of professional skills progression. We illustrate the application of this framework in practice, using the field of applied epidemiology. This framework provides a context for designing and developing high-quality, outcome-based workforce development efforts and evaluating their impact, with implications for academic and public health practice efforts to educate the public health workforce.

Healthy People 2010 is a comprehensive framework for improving the health of Americans, built on the foundation of several decades of predecessor initiatives. Its two overarching goals, to “[i]ncrease the quality and years of healthy life” and “[e]liminate health disparities,” subsume 28 focus areas and comprise 955 objectives and subobjectives. This review evaluates progress toward meeting the Healthy People 2010 program's challenging agenda in the context of leading health indicator (LHI) measures, developed by the Department of Health and Human Services (DHHS), augmented by additional objectives for a total of 31 measures. Our evaluation of progress includes analysis of changes in objective values, including progress toward Healthy People 2010 targets, where appropriate, and analysis of changes in disparities. The Healthy People 2010 LHI measures suggest that although some progress has been made, there is much work to be done toward the Healthy People 2010 targets and both overarching goals.

Recognizing the public's health is the outcome of dynamic, adaptive, and complex systems of agencies; infrastructure, relationships, and interactions that dictate how to improve health outcomes; and reducing health risks in a population is based on systems thinking and evidence. New methods such as network analysis and public health practice–based research networks demonstrate the potential for new insight to our understanding of how systems and infrastructure influence population health. We examine advances in public health systems research since 1988 and discuss the relevance of this type of research to public health practice. We assess the current infrastructure for conducting public health systems research, suggest how the research infrastructure can be improved, and conclude with a discussion of how health reform in the United States will require research focused on understanding the adaptive complexity inherent in public health and health care systems and strengthening the systems research infrastructure.