Epidemiologic Evidence in Toxic Torts

Implications for General Causation

Toxicogenomics and related techniques study how exposure to suspected toxins interacts with variable genetic material to produce, or not produce, toxic effects.¹²² Exposure may result in direct alteration of coding DNA sequences, in alteration of epigenetic factors, or in alteration of gene expression. Such alterations may serve as biomarkers of exposure or, if the alterations indicate or accompany clinical manifestations, as biomarkers of effect.

Valid biomarkers of exposure or effect could importantly supplement other evidence of general causation in toxic tort cases. Conceivably, as with other evidence of a toxic agent's mechanism of action, toxicogenomic evidence could suffice to support a finding of general causation even in the absence of epidemiologic support, particularly if limitations of power or other reasons explain the lack of epidemiologic evidence.

Alternatively, toxicogenomics could identify biomarkers of susceptibility—genetic or epigenetic variations that alter an individual's risk of developing disease after toxic exposure. Such variations could also be detected by genetic epidemiology studies, which extend the methods of classical epidemiology by considering genetic variability or using biomarkers to measure at least some properties of the sampled population.¹²³ The ability to take into account variations across genotypes in susceptibility to the toxic effects of exposure may be among the most important implications of these techniques to toxic tort cases. Discerning such differences could provide vital information in a case of an agent-disease link that yields no association or a small association when investigated without accounting for genetic variability. Some studies have shown, for example, that the degree to which exposure to tobacco smoke increases breast cancer risk varies substantially across genotypes of the NAT2 gene.¹²⁴

Of course, if toxicogenomic studies observe no effect of an exposure, or genetic epidemiology studies find no association between exposure and disease independent of genotype, defendants would use the research to argue against a finding of general causation. Regardless of whether a plaintiff or defendant introduces expert testimony based on toxicogenomic or genetic epidemiologic studies, however, all involved—testifying experts, attorneys, and judges—should appreciate that such studies will not necessarily eliminate uncertainty and controversy concerning general causation. Questions may still be raised about the inferences needed from experimental toxicogenomic systems to actual people and real-world exposures, and about inadequate power, bias, confounding, and other methodological difficulties that may afflict genetic epidemiologic studies no less than traditional epidemiologic research.

Regards

Jun Ray

Assistant Mnaging Editor

Environmental Toxicology and Studies Journal