Applying new biotechnologies to the study of occupational cancer—a workshop summary - Workshop Summary

Environmental Health Perspectives, March 15, 2004 by Mark Toraason, Richard Albertini, Steven Bayard, William Bigbee, Aaron Blair, Paolo Boffetta, Stefano Bonassi, Steven Chanock, David Christiani, David Eastmond, Samuel Hanash, Carol Henry, Fred Kadlubar, Frank Mirer, Daniel Nebert, Stephen Rapport, Kathleen Rest, Nataniel Rothman, Avima Ruder, Russell Savage, Paul Schulte, Jack Siemiatycki, Peter Shields, Martyn Smith, Paige Tolbert, Roel Vermeulen, Paolo Vineis, Sholom Wacholder, Elizabeth Ward, Michael Waters, Weston Ainsley

As high-throughput technologies in genomics, transcriptomics, and proteomics evolve, questions arise about their use in the assessment of occupational cancers. To address these questions, the National Institute for Occupational Safety and Health, the National Cancer Institute, the National Institute of Environmental Health Sciences, and the American Chemistry Council sponsored a workshop 8-9 May 2002 in Washington, DC. The workshop brought together 80 international specialists whose objective was to identify the means for best exploiting new technologies to enhance methods for laboratory investigation, epidemiologic evaluation, risk assessment, and prevention of occupational cancer. The workshop focused on identifying and interpreting markers for early biologic effect and inherited modifiers of risk. Key words: biomarkers, chemical exposure, epidemiology, gene-environment interactions, genomics, occupational cancer, polymorphisms, proteomics, risk assessment, toxicogenomics. Environ Health Perspect 112:413-416 (2004). doi: 10.1289/txg.6343 available via http://dx.doi.org/[Online 14 January 2004]

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The National Occupational Research Agenda (NORA) was established by the National Institute for Occupational Safety and Health (NIOSH) in 1996 with input from more than 500 organizations and individuals. Since its inception, NORA has become a prototype for advancing research in the area of worker safety and health. It is the largest single source of support for 21 occupational research priority areas. The goal of the cancer research methods priority area is to identify, evaluate, and recommend new technologies designed to better control and help investigators understand occupational carcinogenesis. This ongoing effort has coincided with a revolution in biology. The human genome map has just been completed, and it has arrived with a wealth of new biologic methods that drove or were driven by the goal to complete the mapping. Despite this increase in new technologies and methods, they have yet to be applied fully to occupational cancer research (Ward et al. 2003). To address this gap, a workshop, "Applying New Biotechnology to the Study of Occupational Cancer, "was sponsored by NIOSH in conjunction with the National Cancer Institute (NCI), the National Institute of Environmental Health Sciences (NIEHS), and the American Chemistry Council (ACC). The workshop brought together researchers studying worker populations and those developing and validating new biotechnologies. The workshop focused on four topics: a) the challenge of applying new biotechnologies to the study of occupational cancer, b) markers of early biologic effect, c) inherited modifiers of risk, and d) applying genetic biomarkers to human studies.

Challenge of Applying New Biotechnologies to the Study of Occupational Cancer

Epidemiology in the 21st century. A primary challenge in applying new biotechnologies to occupational cancer research is including them within the framework of classic studies of occupational exposure and effect. Historically, occupational studies have helped identify many of the recognized environmental carcinogens, resulting in reduced exposure for both workers and the general population. Studies of carcinogens in occupational populations were facilitated by the availability of records of employees and the high and prolonged exposures they experienced, which often resulted in high relative risks for specific cancers. Challenges to occupational cancer epidemiology in the 21st century relate to the changing nature of the workplace and the complexity of the exposures. As a result of regulations and industry efforts, exposure levels are much lower than in the past. Many exposures are mixtures, and many industries involve exposures to an ever-changing and diverse array of substances. These changes create the need for more sensitive measures to detect cancer risks. To move the field of occupational cancer research forward, it will be necessary to a) conduct more studies of occupational cancer among women and minorities, as these populations have been ignored in the past; b) perform quantitative exposure assessments, as qualitative exposure assessments that rely on general classification of occupation are not good enough; c) examine interactions between occupational exposures and nonoccupational exposures, as cancer is a multi-faceted disease; d) focus on biologic tissues and mechanisms of action and incorporate gene--environmental assessments into traditional exposure disease paradigms used in epidemiology; and e) integrate epidemiology, toxicology, genetics, and quantitative exposure assessment.

The promise of new biotechnologies. The progression from exposure to disease is typically expressed as a continuum of environmental exposure [right arrow], internal dose [right arrow] biologically effective dose [right arrow] early biologic effect [right arrow] altered structure and function [right arrow] and finally clinical disease. Each step is affected by a person's susceptibility, and the continuum provides multiple opportunities for application of biomarkers for early prediction of disease. Although applicable to biomarkers of exposure, the new technologies apply primarily to biomarkers of early effect and susceptibility. Biomarkers that measure early effect and susceptibility can be used in selecting study cohorts, assessing participant compliance, or determining intervention effectiveness. The effective use of biomarkers include optimizing reliability, precision, accuracy, and validity. Not all biomarkers are suitable for all purposes and are likely to be imperfect in any single setting. The greatest potential for new biomarkers of early effect in occupational hazard assessment lies in toxicogenomics, which can be defined as a field of study that examines how the entire genome responds to toxicants or other environmental hazards. Toxicogenomics applies genomics, gene and protein expression profiling, metabolite profiling or metabonomics, and bioinformatics to understand gene--environment interactions and disease. The many genomic-related technologies, often referred to simply as "omics," allow exploration of multiple interactions between genetic and environmental factors. This exploration will improve the understanding of mechanisms of action, clarify the use and limitations of surrogate models, enhance predictive toxicology and screening, and better characterize susceptible populations.