TGF-α Expression as a Potential Biomarker of Risk Within the Normal-appearing Colorectal Mucosa of Patients with and without Incident Sporadic Adenoma

• Type of Material: Article
• Authors: Carrie R. Daniel, Emory University; Roberd M Bostick, Emory University; W Dana Flanders, Emory University; Qi Long, Emory University; Veronika Fedirko, Emory University; Eduard Sidelnikov, Emory University; March E. Seabrook, Consultants in Gastroenterology
• Language: English
• Date: 2009-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 American Association for Cancer Research.
• Final Published Version (URL): http://cebp.aacrjournals.org/content/18/1/65.long
• Title of Journal or Parent Work: Cancer Epidemiology, Biomarkers and Prevention
• ISSN: 1055-9965
• Volume: 18
• Issue: 1
• Start Page: 65
• End Page: 73
• Grant/Funding Information: Fullerton Foundation, Franklin Foundation, and Georgia Cancer Coalition Distinguished Scholar Award (R.M. Bostick).
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Oncology; Health Sciences, Public Health

Abstract

Background: Transforming growth factor-α (TGF-α), a stimulatory growth factor and member of the epidermal growth factor family, is a mediator of oncogenesis and malignant progression in colorectal carcinogenesis. Limited evidence suggests its utility as a growth-related biomarker of risk for colorectal cancer. Methods: We measured expression of TGF-α in biopsies of normal-appearing colorectal mucosa using automated immunohistochemistry and quantitative image analysis in a subsample of 29 cases and 31 controls from a colonoscopy-based case-control study (n = 203) of biomarkers of risk for incident sporadic colorectal adenoma. Diet, lifestyle, and medical history were assessed with validated questionnaires. Results: TGF-α expression in the rectum was 51% higher in cases compared with controls (P = 0.05) and statistically significantly associated with accepted risk factors for colorectal neoplasms (36% lower among nonsteroidal anti-inflammatory drug users, 49% lower among women using hormone replacement therapy, 79% higher among persons with a family history of colorectal cancer). Conclusions: TGF-α expression in the normal-appearing rectal mucosa shows promise as an early, potentially modifiable biomarker of risk for colorectal cancer.