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About the Authors:
Daniel Gusenleitner
Affiliations Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America, Department of Computational Biomedicine, Boston University Medical Campus, Boston, Massachusetts, United States of America
Scott S. Auerbach
Affiliation: Biomolecular Screening Branch, Division of the National Toxicology Program at the National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, United States of America
Tisha Melia
Affiliation: Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America
Harold F. Gómez
Affiliation: Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America
David H. Sherr
Affiliation: Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, United States of America
Stefano Monti
* E-mail: [email protected]
Affiliations Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America, Department of Computational Biomedicine, Boston University Medical Campus, Boston, Massachusetts, United States of America
Introduction
[T]he development of truly useful, predictive tests of human carcinogens still lies in the future.
– R.A. Weinberg [1]
Despite an overall decrease in mortality from cancer, about 41% of Americans will be diagnosed with the disease and about 21% will die from it [2]. The incidence of certain cancers is increasing for unknown reasons, and there is substantial evidence suggesting that inherited genetic factors make only a minor contribution [3], while the percentage of cancer cases that can be attributed to infectious diseases remains stable at about 16–18% [4]. It has thus been widely hypothesized that accumulating environmental chemicals play a significant role in sporadic cancer [5]–[7]. There is also growing recognition that the role played by environmental pollutants in human cancer is under-studied, and that more formal approaches to the analysis of the biological consequences of prolonged exposure to pollutants are needed [8], [9].
High-throughput genomic approaches have been successfully applied toward the elucidation of the molecular mechanisms of cancer initiation and progression, to the identification of novel therapeutic targets, and to the development of diagnostic and prognostic biomarkers, resulting in thousands of publications. However, their application to the study of the environmental causes of cancer has not received as much attention.
Standard approaches to carcinogen testing have adopted the 2-year rodent bioassay (2YRB) as the de facto “gold-standard”. The 2YRB requires, for each compound, the use of more than 800 rodents and...