Insulin-like growth factor binding protein-3: relationship to the development of gastric pre-malignancy and gastric adenocarcinoma (United Kingdom)

Cancer Causes Control. 2004 Mar;15(2):211-8. doi: 10.1023/B:CACO.0000019510.96285.e9.


IGF family proteins play a pivotal role in regulating cell growth and apoptosis in normal and tumour tissues. IGFBP-3 is the major binding protein of IGFs and modulates the bioactivity of IGFs. To examine the role of IGFBP-3 in gastric cancer, an IGFBP3 promoter polymorphism, and serum and gastric mucosal levels of IGFBP-3 were assessed in two independent groups of patients (396 and 117 patients, respectively) with gastroduodenal diseases. There was no significant association between IGFBP-3 polymorphism and different gastroduodenal diseases ( p = 0.6), but a significantly higher frequency of CC, a genotype related to lower levels of serum IGFBP-3 previously, were observed in patients with antral intestinal metaplasia when compared with those without this pre-malignancy ( p = 0.04). Similarly, data from another independent group of patients further showed that patients with antral or corpus intestinal metaplasia had significantly lower serum levels of IGFBP-3 than those without these changes ( p = 0.03 and 0.04, respectively). Furthermore, the percentage of positive IGFBP-3 staining in tumour tissue was significantly higher in patients with well or moderately differentiated tumours than those with poorly differentiated tumours ( p = 0.04), indicating that IGFBP-3 may be associated with a better prognosis. In conclusion, our study suggests that IGFBP-3 may be protective against the development of gastric adenocarcinoma by preventing the formation of intestinal metaplasia and improve the prognosis of gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology*
  • Adenocarcinoma / genetics
  • DNA / chemistry
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Precancerous Conditions / etiology*
  • Precancerous Conditions / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / genetics
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • United Kingdom


  • Insulin-Like Growth Factor Binding Protein 3
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • DNA