Utilization of Biomarker Data for Clinical and Environmental Intervention. The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Christiani, David C. 1996. Utilization of biomarker data for clinical and environmental intervention. Environmental Health Perspectives 104: 921-925. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:4882984 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Morm Utilization of Biomarker Data for Clinical are difficult to detect in epidemiologic studies because the relative risk for low-level and Environmental Intervention exposed, versus nonexposed, people is only slightly elevated (2). Complicating this David C. Christiani problem is the generic aim ofexposure-dose Occupational Medicine and Epidemiology, Harvard School of Public assessment in field studies: imprecise methodology to quantify exposures, espe- Health, Boston, Massachusetts cially those which may have occurred years bias. Of the 189 air toxics listed in the Clean Air Act, a substantial number are important in potentially ago, can lead to misclassification and causing adverse health effects in several organ systems. Although the major health effects are Moreover, the temporal pace of the tradi- manifested as respiratory diseases, especially airways disease, these agents may cause cancer tional cohort study, which must await data and premature mortality, probably from cardiopulmonary disease. Validated biologic markers may from large populations exposed for long be useful in identifying early effects to improve our understanding of exposure-response relation- periods, has become an obstacle. Regulators, ships and clarify susceptibility. However, the knowledge obtained from epidemiologic studies uti- clinicians, and the public are too impatient lizing these new molecular tools will reduce morbidity and mortality from air toxics only when to await such "natural experiments," and they can be applied effectively in the prevention and control of disease. Intervention strategies seek shorter term strategies for studies and using these markers can be used to identify etiologic factors and assess the effectiveness of quicker solutions (2). exposure reduction, and, in some instances, chemoprevention. This paper illustrates examples of Since the concept of molecular epi- these intervention strategies and reviews the current strengths and limitations of environmental demiology was popularized in the early molecular epidemiology in controlling disease caused by air toxics. Environ Health Perspect 1980s (3) to describe an evolving approach 104(Suppl 5):921-925 (1996) to human environmental health research, Key words: biomarkers, intervention strategies, air toxics, molecular epidemiology much work has been done on biomarker development. The theoretical foundation of this work relies on three biologic tenets: a) early biologic effects from a toxic expo- Introduction sure are more prevalent and detectable in This symposium has described the current Much of what we have learned about the population at risk than clinical disease is; state-of-the-art research on biologic mark- the human health effects of toxic exposures b) with technological advances, many toxins ers that may be relevant to air toxics. The has come from epidemiologic studies of can be either directly quantified in body goal of such research is practical: to apply exposed workers and from toxicologic fluids or tissues or indirectly measured by relevant and valid biomarkers of exposure, studies on animals. Astute clinical observa- identification of some predictable, dose- effect, and susceptibility to epidemiologic tions and animal testing have provided the related (early) biological response; and studies of populations exposed to air toxics basis for large-scale epidemiologic studies c) either (or both) of the above may be and to incorporate the resulting informa- of workers exposed to toxic agents such as influenced by susceptibility phenomena tion into public health actions aimed at asbestos and vinyl chloride. The risk of dis- (heritable or nonheritable), which can also controlling exposures and adverse health eases caused by such agents are markedly be accounted for with recent advances in effects. Studies that incorporate the use of increased in exposed workers who have molecular biology. Combining these three biologic markers in human populations are usually been exposed to concentrations principles, a new approach to environmental often referred to as "molecular epidemio- much higher than the general population. health research has emerged that expands on logic studies." A conceptual approach to the However, in the case of community air the traditional epidemiologic paradigm. application of biologic markers to human pollution studies, new challenges have In addition to improved measures of populations is shown in Figure 1. The ulti- arisen. First, we must find ways to eluci- exposure, response, and susceptibility, mate goal for environmental molecular date factors that modestly increase disease side benefits emerge that have direct rele- epidemiology is to fulfill the promise of risk (1). Though such causes could be vance for intervention (4): contributions preventive medicine: environmental disease extremely important from a public health to the understanding of pathogenic mecha- prevention and control. point of view, these kinds of associations nisms at the tissue, cellular, or molecular This paper was presented at the Conference on Air Toxics: Biomarkers in Environmental Applications Susceptibility held 27-28 April 1995 in Houston, Texas. Manuscript received 24 May 1996; manuscript accepted 5 June 1996. This work was supported by National Institutes of Health grants ES/CA 06409 and ES00002. Address correspondence to Dr. D.C. Christiani, Occupational Medicine and Epidemiology, Harvard School of Public Health, 665 Huntingdon Avenue, Boston, MA 02115. Telephone: (617) 432-3323. Fax: (617) 432-0219. E-mail: [email protected] Abbreviations used: PAH, polycyclic aromatic Figure 1. Relationship of biomarkers to exposure, susceptibility, and disease. Adapted from the National Research hydrocarbon; NAT, /\Nacetyltransferase; IL, interleukin. Council (36). Environmental Health Perspectives * Vol 104, Supplement 5 * October 1996 921 D.C. CHRISTIANI levels, potential for more accurate and eti- simultaneously. Lead toxicity provides an of smokers and nonsmokers. DNA adducts ologic classification of environmental dis- example of this combined approach: regula- are formed when chemical carcinogens eases, and the possibility that recognition tory measures are concurrently aimed at react with DNA. Several methods of of early adverse effects could prompt reducing the whole population's exposure detecting adducts in lung and surrogate tis- strategies for secondary prevention or and at monitoring internal dose (blood lead) sue, including the sensitive 32P-postlabeling disease modification. ofindividual children by pediatricians. procedure for PAHs, have been described in Biomarker research does not exist in a These generic intervention strategies detail. Among the class of pulmonary car- vacuum. Its usefulness can only be real- have also been important in cancer preven- cinogens known as PAHs, benzo[a]pyrene ized when it translates into prevention tion and control, such as control of occupa- forms DNA adducts in the lung that are strategies to protect public health. In this tional bladder cancer by substitution of associated with smoking. Recent research short review, I describe how biomarkers benzidine dyes with less toxic compounds; indicates that surrogate tissue (blood may be used in clinical and environmental control of coke-oven-induced lung cancers mononuclear cells) adducts reflect target interventions. by engineering controls and personal protec- organ (lung) adducts in cancer patients tion; and control of bis-chloromethyl ether (Figure 2) (6). Such validation will permit Intervention Approaches induced lung cancer by elimination of that assessment of interventions such as smoking Intervention approaches in public health compound in plastic and glass production. cessation, chemoprevention, and elimina- can be characterized as either the high-risk tion of passive smoking exposures in reduc- or population approach (5). The high-risk Lung Cancer ing PAH-DNA adducts in peripheral approach aims to detect individuals at high Tobacco smoke is implicated in up to 85% blood mononuclear cells. Use of blood risk by using a biologic marker and lower- of the more than 150,000 lung cancer cases adducts will also permit epidemiologic ing risk by clinical intervention or other that occur in the United States every year. study of large populations exposed to action. Usually, the risk marker is moni- Despite the strong and consistent epidemi- PAHs in air pollution. tored concurrently with the intervention. ologic evidence linking tobacco smoking to Although the presence of PAH-DNA In contrast, population approach aims to cancer, the majority of smokers do not adducts has not been definitely associated reduce the overall occurrence of a risk fac- develop lung cancer. Individual variability with lung cancer, it is clear that these tor (exposure) in a population. in carcinogen metabolism may explain dif-