TY - JOUR
T1 - Transforming growth factors and receptor as potential modifiable pre-neoplastic biomarkers of risk for colorectal neoplasms
AU - Tu, Huakang
AU - Ahearn, Thomas U.
AU - Daniel, Carrie R.
AU - Gonzalez-Feliciano, Amparo G.
AU - Seabrook, March E.
AU - Bostick, Roberd M.
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc..
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Increased colorectal epithelial cell proliferation is an early, common event in colorectal carcinogenesis. We conducted a pilot, colonoscopy-based case-control study (n=49 cases, 154 controls) of incident, sporadic colorectal adenoma to investigate endogenous cell growth factors and receptor, as well as the balance of growth factors, as potential modifiable pre-neoplastic biomarkers of risk for colorectal neoplasms. We measured transforming growth factor alpha (TGFα), TGFβ1, and TGFβ receptor II (TGFβRII) expression in normal-appearing mucosa from the rectum, sigmoid colon, and ascending colon using automated immunohistochemistry and quantitative image analysis. Diet and lifestyle were assessed via questionnaires. The mean ratio of rectal TGFα to TGFβ1 expression and mean rectal TGFα expression were, respectively, 110% (P=0.02) and 49% (P=0.04) higher in cases than in controls, and associated with a more than two-fold (OR 2.42, 95% CI 0.85-6.87) and a 62% (OR 1.62, 95% CI 0.63-4.19) higher risk of colorectal adenoma. TGFβ1 and TGFβRII expression were 6.7% (P=0.75) and 7.2% (P=0.49), respectively, lower in cases than in controls. The TGFα/TGFβ1 expression ratio was 105% higher among smokers than among non-smokers (P=0.03). These preliminary data suggest that the balance of TGFα and TGFβ1 expression, and to a lesser extend TGFα alone, in the normal-appearing rectal mucosa may be directly associated with risk for incident, sporadic colorectal neoplasms, as well as with modifiable risk factors for colorectal neoplasms.
AB - Increased colorectal epithelial cell proliferation is an early, common event in colorectal carcinogenesis. We conducted a pilot, colonoscopy-based case-control study (n=49 cases, 154 controls) of incident, sporadic colorectal adenoma to investigate endogenous cell growth factors and receptor, as well as the balance of growth factors, as potential modifiable pre-neoplastic biomarkers of risk for colorectal neoplasms. We measured transforming growth factor alpha (TGFα), TGFβ1, and TGFβ receptor II (TGFβRII) expression in normal-appearing mucosa from the rectum, sigmoid colon, and ascending colon using automated immunohistochemistry and quantitative image analysis. Diet and lifestyle were assessed via questionnaires. The mean ratio of rectal TGFα to TGFβ1 expression and mean rectal TGFα expression were, respectively, 110% (P=0.02) and 49% (P=0.04) higher in cases than in controls, and associated with a more than two-fold (OR 2.42, 95% CI 0.85-6.87) and a 62% (OR 1.62, 95% CI 0.63-4.19) higher risk of colorectal adenoma. TGFβ1 and TGFβRII expression were 6.7% (P=0.75) and 7.2% (P=0.49), respectively, lower in cases than in controls. The TGFα/TGFβ1 expression ratio was 105% higher among smokers than among non-smokers (P=0.03). These preliminary data suggest that the balance of TGFα and TGFβ1 expression, and to a lesser extend TGFα alone, in the normal-appearing rectal mucosa may be directly associated with risk for incident, sporadic colorectal neoplasms, as well as with modifiable risk factors for colorectal neoplasms.
KW - Biological markers
KW - Colorectal neoplasms
KW - TGFα
KW - TGFβ receptor II
KW - TGFβ<inf>1</inf>
UR - http://www.scopus.com/inward/record.url?scp=84938968816&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938968816&partnerID=8YFLogxK
U2 - 10.1002/mc.22152
DO - 10.1002/mc.22152
M3 - Article
C2 - 24719252
AN - SCOPUS:84938968816
SN - 0899-1987
VL - 54
SP - 821
EP - 830
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 9
ER -