Field defects in progression to adenocarcinoma of the colon and esophagus

Carol Bernstein*
Department of Microbiology and Immunology
College of Medicine, University of Arizona, Tucson AZ 85724
Tel: 1-520-626-6069
Fax: 1-520-626-2100 (fax)
E-mail: Bernstein3@earthlink.net

Harris Bernstein
Department of Microbiology and Immunology
College of Medicine, University of Arizona, Tucson AZ 85724
E-mail: Bernstein3@earthlink.net

Claire M. Payne
Department of Microbiology and Immunology
College of Medicine, University of Arizona, Tucson AZ 85724
E-mail: Cpayne@u.Arizona.edu

Harinder Garewal
Department of Internal Medicine, Section of Hematology/Oncology,
Arizona Cancer Center, Tucson AZ 85724 and
Section of Gastroenterology, Tucson Veteran Affairs Medical Center, Tucson AZ 85723
E-mail: Hgarewal@azcc.arizona.edu

* Corresponding author

Financial support: This work was supported in part by NIEHS grant #ES06694 (Experimental Pathology Core; #ES06694 Southwest Environmental Health Sciences Center); NIH Institutional Core Grant #CA23074 to Arizona Cancer Center; NIH PPG #CA72008; Arizona Disease Control Research Commission Grant #10016: Innovite, Inc. (Tigard, Oregon) and Biomedical Diagnostics and Research, Inc. (Tucson, Arizona).

A field of defective tissue (field defect) appears to be an early stage in the progression to adenocarcinoma of both the colon and the esophagus. In both cases the field is comprised of cells characterized by resistance to induction of apoptosis, aberrant increased proliferation and genomic instability. Specific mutations and epimutations occur in both types of field. Also there is evidence for aberrant overexpression or underexpression of specific proteins. Most of these early molecular alterations appear to promote either enhanced apoptosis resistance, proliferation, or genomic instability. The molecular alterations that are present early are often, but not always, also present to an even greater degree in the cancer itself. Many of the important events in the development of colonic and esophageal adenocarcinoma first occur in tissues that are histologically neither dysplastic nor malignant. The identification of early molecular defects in morphologically normal appearing tissue is paramount in identifying subjects at high risk for cancer.