BOX 6-3Summary of Research Issues and Potential Applications

Questions to be answered

  • How does human genetic variation influence transcriptomic, proteomic, or metabonomic patterns of response to toxic agents?
  • Is genetic susceptibility to different classes of toxicologic agents due to a few key genes or does it represent a continuum of multigenic risk?
  • How many drugs fail clinical trials because of a toxic response in a genetically susceptible subgroup?
  • How do we best use existing environmental cohort studies to identify gene-environment interactions with toxicogenomic approaches?
  • How can toxicogenomic research be translated and tested to reduce health risks for the public?

Gaps in knowledge

  • The influence of human genetic and epigenetic variation on transcriptomic, proteomic, and metabonomic studies of toxicologic agents is unknown.
  • Although animal models and established human cell lines offer some insight into human response to toxic agents, questions remain about how well these studies indicate toxicologic risk in free-living humans.
  • Cohort study estimates of the relative risk of disease for most genotype-environment combinations is lacking.
  • Multigenic predictive models of toxicologic risk that integrate pleiotropic and polygenic networks of interactions among genes, environments, and other factors have yet to be developed.

How can this technology be applied?

  • Identifying genetic variations associated with environmental susceptibility to toxicity can be used to identify at-risk subgroups of the population through genetic testing.
  • Developing multigenic models of toxicologic risk can be used to better understand the distribution of risk in a population and can be used in risk communication efforts to reduce exposure and disease.

From: 6, Application to Analyzing Variation in Human Susceptibility

Cover of Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment
Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment.
National Research Council (US) Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology.
Washington (DC): National Academies Press (US); 2007.
Copyright © 2007, National Academy of Sciences.

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