Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas

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  • Keku, Temitope
    • Affiliation: School of Medicine, Department of Medicine
  • Sandler, Robert
    • Affiliation: School of Medicine, Department of Medicine
  • Simmons, James G
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
  • Galanko, Joseph
    • Affiliation: School of Medicine, Department of Medicine
  • Woosley, John T
    • Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
  • Proffitt, Michelle
    • Affiliation: School of Medicine, Department of Medicine
  • Omofoye, Oluwaseun
    • Affiliation: School of Medicine, Department of Medicine
  • McDoom, Maya
    • Affiliation: School of Medicine, Department of Medicine
  • Lund, Pauline Kay
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
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. Conclusion 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.
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  • Article
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  • In Copyright
Rights holder
  • Temitope O Keku et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Cancer
Journal volume
  • 8
Journal issue
  • 1
Page start
  • 143
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2407
Bibliographic citation
  • BMC Cancer. 2008 May 22;8(1):143
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • July 15, 2016

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