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Janet Gray, Ph.D.
Janet Gray, Ph.D.

As author of our 2008 and 2010 State of the Evidence reports, Dr. Gray drives the science behind all our work.

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Genomic Studies


Definition: The study of genes and their functions

Classification: Genomic

The past decade has seen an explosion of research centered on the changes in specific gene activity. This new field known as genomics began with the deciphering of the code of the human and mouse DNA sequences, along with the sequences of hundreds of other mammalian and non-mammalian species. Toxicogenomics is the new research field that allows scientists to identify and describe repeatable changes in specific gene activities in the presence of different exposures, and to then study the relationships between these genetic changes and health outcomes (Jayapal, 2010; Zarbl, 2007). Recent technical developments allow for screening of gene expression in clinically derived tissues, from experimental animal models, or from cell systems treated with various environmental chemicals.

Use of molecular profiling and genomic approaches in studying breast cancer have underscored the complexity of the disease, with different genomic profiles arising depending on breast cell type (e.g., stromal vs. epithelial), and tumor characteristics like size of tumor, node involvement, receptor status, and menstrual or estrous cycle phase (Sims, 2009). These studies have helped confirm that clinically-derived subtypes of breast cancer (based upon prognosis, receptor status and response to treatment) also differ at the genetic level (Curtis, 2012). Scientists studying changes in breast tissue over the course of cancer development are using this new information about genetic differences to better understand the process of carcinogenesis, the factors responsible for inducing those processes, and possible interventions (Rennstam, 2006).

An ultimate goal will be to combine genomic data with epidemiological studies of women (and men) with different genetic, reproductive, lifestyle and environmental toxicant exposures and their health histories, including history of breast cancer (Lund, 2008). This could provide a deeper understanding of changes in gene expression over the lifespan and among different populations.


Part of a larger national study, the Norwegian Woman and Cancer post-genome cohort study involves following about 50,000 women participants born between 1943 and 1957. They have answered extensive medical, reproductive history and lifestyle questionnaires and given blood samples that can be used for extensive gene-expression profiling analysis. Should a participant be diagnosed with breast cancer, blood samples and tumor biopsy tissues will be analyzed using similar gene expression assays and compared with samples from healthy women (Dumeaux, 2008).


DNA array technology allows for the screening of literally thousands of genes and their products at the same time. This is an extraordinarily powerful descriptive tool that allows scientists to develop hypotheses about changes in cell activity at the gene-expression level, and the interactions between numerous factors, without needing to rely on large number of clinical or animal samples. The sheer quantity of data requires investigators to make choices about which genes and gene products to focus on—a decision process that may vary greatly from lab to lab, especially since there is considerable redundancy in gene regulation of critical cell pathways implicated in breast cancer. The ability to go from screening of thousands of chemicals to interpretation of biological implications remains a goal for the years ahead, but the initial progress from this technology is very promising (Tice, 2013).

Most important, new applications of this genomics approach are being developed to study the effects of low-dose exposures to environmental toxicants on gene expression, through both traditional transcription studies as well as examination in epigenetic processes that have been implicated in lifetime accrual of added risk for cancer development (Vineis, 2009). These strategies can examine multiple mixtures of environmental factors as they affect cells with different genetic and epigenetic histories.


While these new genetic data will be informative for better understanding the complexity of disease, the relevance of gene profile data for prevention, diagnosis or treatment of breast cancer in individual women is less promising, although particular profiles may help in the development of individualized prevention strategies (Eccles, 2013). Unfortunately, without changes in occupational, consumer product and other environmental sources of toxicants associated with breast cancer, this knowledge may not be helpful in diminishing risk attributable to these critical sources.

In addition, cell activity is influenced not only by genes, but also by the cellular microenvironment and the external environment. The body has a vast array of checks and balances, such as the capacity to repair genes or to program cell death among severely damaged cells, which may not be captured in gene studies.

Finally, studies of gene-environment interactions are only as strong as the collected knowledge about both genes and environmental exposures. Thus toxicogenomics knowledge is limited by significant gaps in basic knowledge about chemicals, both individually and in mixtures.