Assessment of research models for testing gene-environment interactions

Throughout the last century, possible effects of exposure to toxicants, nutrients or drugs were examined primarily by studies of groups or populations. Individual variation in responses was acknowledged but could not be analyzed due to lack of information or tools to analyze individual genetic make-ups and lifestyle factors such as diet and activity. The Human Genome, Haplotype Map, 1000Genomes, and Human Variome Projects are identifying and cataloging the variation found within humans. Advances in DNA sequencing technologies will soon permit the characterization of individual genomes in clinical and basic research studies, thus allowing associations to be made between an individual genotype and the response to a particular exposure. Such knowledge and tools have generated a significant challenge for scientists: to design and conduct research studies that account for individual genetic variation. However, before these studies are done in humans, they will be performed in various in vivo and in vitro models. The advantages and disadvantages of some of the model test systems that are being used or developed in relation to individual genetic make-up and responses to xenobiotics are discussed.