Description

Genetic Alterations in Cancer (GAC)

Comprehensive literature search strategies are used to identify studies of gene alterations in tumors associated with exposure to specific environmental agents. The search strategies are applied to the peer-reviewed literature and journal articles that met three critical criteria are selected for data extraction:

1. A description of the tumor(s) and indication of which were associated with exposure to a specific agent (e.g., occupational exposure or general population from epidemiologic or case series studies) and which were spontaneous
2. A molecular analysis of the tumor sample for genetic alterations; and (3) the identification of the affected gene(s) and description of the gene change(s)

Data from hundreds of studies of gene mutations, loss of heterozygosity (LOH), or homozygous deletions (HOD) in numerous types of tumors associated with exposure to chemical, physical, or biological agents, are provided in the GAC database. Data from studies in humans, mice, and rats are included. All information is procured from original studies published in the peer-reviewed literature.

Data mining features for querying the database summarize results in data tables and graphic profiles that show the incidence (percent) of tumors reported to have any type of genetic alteration for each gene studied. Detailed data tables are provided that show specific base changes reported for affected codons based on individual study subjects. The age or age range and gender of each study subject are also displayed. Corresponding reference lists are available with links to their PubMed abstracts.

To maintain consistency during data entry, controlled vocabularies are used for all data fields. Pull-down menus are used to select the agent, species, strain, tumor type, and gene. Look-up tables are used to automatically enter exon numbers, codon sequences, alteration descriptions, and amino acid codes, based on the identity of the affected codon and the base change reported. The resources used for developing the controlled vocabularies and look-up tables are presented in the table below.

Data Field	Source	URL
Agent (chemical name, CASRN, & MW)	ChemFinder	http://chemfinder.cambridgesoft.com/ (http://chemfinder.cambridgesoft.com/)
Tumor topography	International Classification of Diseases for Oncology, 2nd Edition	http://www.who.int/ classifications/apps/icd/icd10online/ (http://www.who.int/classifications/apps/icd/icd10online/)
Human morphologies	International Classification of Diseases for Oncology, 2nd Edition	http://seer.cancer.gov/ tools/conversion/ICDO2-3manual.pdf (http://seer.cancer.gov/tools/conversion/ICDO2-3manual.pdf)
Rodent morphologies	NTP Pathology Codes	http://jones.niehs.nih.gov:8080/ pct/ (http://jones.niehs.nih.gov:8080/pct/)
Ethnicity	NCI SEER Program Code Manual, 3rd Edition, 1998	http://seer.cancer.gov/ tools/codingmanuals (http://seer.cancer.gov/tools/codingmanuals)
Tumor grading	The American Joint Commission on Cancer	http://training.seer.cancer.gov/ module_coding_primary/ unit04_guidelines10_rule_g.html (http://training.seer.cancer.gov/module_coding_primary/unit04_guidelines10_rule_g.html)
Tumor staging	The Oncology Channel	http://www.oncologychannel.com/ staging.shtml (http://www.oncologychannel.com/staging.shtml)
Human gene symbols and codon sequences	HUGO Ensembl	http://www.genenames.org/ index.html (http://www.genenames.org/index.html) and http://www.ensembl.org/Homo_sapiens/ (http://www.ensembl.org/Homo_sapiens/)
Mouse gene symbols and codon sequences	Mouse Genome Informatics Ensembl	http://www.informatics.jax.org/ (http://www.informatics.jax.org/) http://www.ensembl.org/Mus_musculus/ (http://www.ensembl.org/Mus_musculus/)
Rat gene symbols and codon sequences	Rat Genome Database and NCBI GenBank	http://rgd.mcw.edu/ genes/ (http://rgd.mcw.edu/genes/) and http://www.ncbi.nih.gov/ entrez/query.fcgi?db=Nucleotide (http://www.ncbi.nih.gov/entrez/query.fcgi?db=Nucleotide)
Amino acid codes	NCBI Standard Code Table	http://www.ncbi.nlm.nih.gov/ Taxonomy/Utils/wprintgc.cgi?mode=t#SG1 (http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=t#SG1)

If a specific base change is not reported, NG (not given) is entered in the alteration description and the exon and codon fields. Summary results from gene mutations and HOD studies show the total number of tumors evaluated, the number of tumors affected, and the incidence (percentage) of tumors with alterations. Results from LOH studies show the total number of tumors in which informative markers were evaluated, the number of tumors in which LOH was reported for one or more of the markers, and the incidence (percentage) of tumors with LOH.

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Human Data

The majority of the human data are from case series studies. Many of the studies include data for both agent-related and sporadic tumors (tumors for which evidence of exposure is unknown or unclear), and in some cases, data from unexposed individuals. Most of the data are from studies of primary tumors; however, some studies also report data for metastatic tumors. Results from metastatic tumors are entered based on the primary tumor topography.

Data from individuals for which exposure to a specific agent associated with tumor development is reported (e.g., personal monitoring, biomarkers of exposure, or questionnaires) are entered in the database under the agent name; if evidence of non-exposure is reported, data are entered under Unexposed (with the study agent ID in parenthesis). If exposure to an exogenous agent is not presented or is unknown, data are entered under Sporadic (with the agent ID in parenthesis). For example, results from studies of skin tumors related to exposure to ultraviolet (UV) radiation are entered under the agent identities: UV-Radiation [tumors from sites known to be exposed to the sun], Unexposed (UV) [tumors from non sun-exposed sites], and Sporadic (UV) [tumor site is not reported]. If there is no mention of exposure to specific agent, the tumors are entered as Spontaneous.

Many chemical exposures are from occupational exposure to a mixture of chemicals of which one is of primary concern. For example, studies of individuals exposed to an agent like benzene may report exposure to a benzene-containing product such as gasoline. In such cases, data are entered under the name of the agent of concern and the total chemical composition is shown in note fields displayed using the [More Details] function along with other study details including exposure description and ethnicity.

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Mouse and Rat Data

Data from studies in mice and rats are entered under the study-agent name or, for results from untreated animals, as spontaneous. Both species and strain are identified for each study. As with the human data, information which describes the experimental conditions (dose, route, exposure time, sample time, and numbers of animals treated and those with tumors) are displayed using the [More Details] function.

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