title: Insulin-like growth factor binding protein-3: relationship to the development of gastric pre-malignancy and gastric adenocarcinoma (United Kingdom).
abstract: 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.
authors.affiliation: Division of Surgery, Level 7, Queens Building, Bristol Royal Infirmary, University of Bristol, Bristol BS2 8HW, UK. zunwuzhang@hotmail.com
authors.forename: Zun-Wu
authors.initials: ZW
authors.lastname: Zhang
authors.forename: Paul V
authors.initials: PV
authors.lastname: Newcomb
authors.forename: Moganaden
authors.initials: M
authors.lastname: Moorghen
authors.forename: Jyoti
authors.initials: J
authors.lastname: Gupta
authors.forename: Roger
authors.initials: R
authors.lastname: Feakins
authors.forename: Paul
authors.initials: P
authors.lastname: Savage
authors.forename: Andrew
authors.initials: A
authors.lastname: Hollowood
authors.forename: Derek
authors.initials: D
authors.lastname: Alderson
authors.forename: Jeff M P
authors.initials: JM
authors.lastname: Holly
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000209:etiology* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D006113:United Kingdom
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA