Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas.
BACKGROUND
IGF binding protein-3 (IGFBP-3) regulates the bioavailability of insulin-like growth factors I and II, and has both anti-proliferative and pro-apoptotic properties. Elevated plasma IGFBP-3 has been associated with reduced risk of colorectal cancer (CRC), but the role of tissue IGFBP-3 is not well defined. We evaluated the association between tissue or plasma IGFBP-3 and risk of colorectal adenomas or low apoptosis.


METHODS
Subjects were consenting patients who underwent a clinically indicated colonoscopy at UNC Hospitals and provided information on diet and lifestyle. IGFBP-3 mRNA in normal colon was assessed by real time RT-PCR. Plasma IGFBP-3 was measured by ELISA and apoptosis was determined by morphology on H & E slides. Logistic regression was used to compute odds ratio (OR) and 95% confidence intervals.


RESULTS
We observed a modest correlation between plasma IGFBP-3 and tissue IGFBP-3 expression (p = 0.007). There was no significant association between plasma IGFBP-3 and adenomas or apoptosis. Tissue IGFBP-3 mRNA expression was significantly lower in cases than controls. Subjects in the lowest three quartiles of tissue IGFBP-3 gene expression were more likely to have adenomas. Consistent with previous reports, low apoptosis was significantly associated with increased risk of adenomas (p = 0.003). Surprisingly, local IGFBP-3 mRNA expression was inversely associated with apoptosis.


CONCLUSIONS
Low expression of IGFBP-3 mRNA in normal colonic mucosa predicts increased risk of adenomas. Our findings suggest that local IGFBP-3 in the colon may directly increase adenoma risk but IGFBP-3 may act through a pathway other than apoptosis to influence adenoma risk.
Keku
Temitope O
TO
Department of Medicine and Center for Gastrointestinal Biology & Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. tokeku@med.unc.edu
Sandler
Robert S
RS
Simmons
James G
JG
Galanko
Joseph
J
Woosley
John T
JT
Proffitt
Michelle
M
Omofoye
Oluwaseun
O
McDoom
Maya
M
Lund
Pauline K
PK
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D017209:Apoptosis; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D013223:Statistics as Topic; D014481:United States
D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger