Genetic, genomic, and bioinformatic tools for studying breast cancer progression

Cancer susceptibility is a complex interaction of an individual's genetic composition and environmental exposures. Huge strides have been made in understanding cancer over the past 100 years, from the recognition of cancer as a genetic disease, to the identification of specific carcinogens, isolation of oncogenes and the recognition of tumor suppressors. Analysis of high-risk familial cancers has led to the discovery of new tumor suppressor genes and important cancer pathways. These families however represent only a small fraction of cancer in the general population. Most cancer instead probably results of an intricate interaction of polymorphic susceptibility genes with the sea of environmental exposures that humans experience. Although the central cadre of cancer genes is known, little is understood about the peripheral genes that likely comprise the polymorphic susceptibility loci. The challenge for cancer genetics is therefore to move forward from the Mendelian genetics of the rare familial cancer syndromes into the field of quantitative trait loci, susceptibility factors, and modifier genes. By identifying the genes that modulate an individual's susceptibility to cancer after an environmental exposure, researchers will be able to gain important insights into human biology, cancer prevention and treatment. The most efficient strategies to identify and characterize modifier loci will likely be those that are transdisciplinary, encompassing a variety of different "-omic" technologies. The application of a "trans-omic" techniques in our laboratory to the study of breast cancer dissemination is presented here as an illustration of the strategy.