TGF-alpha expression as a potential biomarker of risk within the normal-appearing colorectal mucosa of patients with and without incident sporadic adenoma.
BACKGROUND
Transforming growth factor-alpha (TGF-alpha), 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-alpha 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-alpha 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-alpha expression in the normal-appearing rectal mucosa shows promise as an early, potentially modifiable biomarker of risk for colorectal cancer.
Daniel
Carrie R
CR
Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia 30322, USA.
Bostick
Roberd M
RM
Flanders
William Dana
WD
Long
Qi
Q
Fedirko
Veronika
V
Sidelnikov
Eduard
E
Seabrook
March E
ME
D000236:Adenoma / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D004032:Diet; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012044:Regression Analysis; D012307:Risk Factors; D011795:Surveys and Questionnaires; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016211:Transforming Growth Factor alpha