title: Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas.
abstract: 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.
authors.affiliation: 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
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: James G
authors.initials: JG
authors.lastname: Simmons
authors.forename: Joseph
authors.initials: J
authors.lastname: Galanko
authors.forename: John T
authors.initials: JT
authors.lastname: Woosley
authors.forename: Michelle
authors.initials: M
authors.lastname: Proffitt
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Omofoye
authors.forename: Maya
authors.initials: M
authors.lastname: McDoom
authors.forename: Pauline K
authors.initials: PK
authors.lastname: Lund
mesh_terms: 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
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger