Promoter -202 A/C polymorphism of insulin-like growth factor binding protein-3 gene and non-small cell lung cancer risk

Int J Cancer. 2006 Jan 15;118(2):353-6. doi: 10.1002/ijc.21339.


Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits the mitogenic and antiapoptotic activity of insulin-like growth factor (IGF) by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Therefore, we attempted to ascertain whether the A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC). Our study included 209 NSCLC patients and 209 age-, gender- and smoking status-matched control subjects. The frequencies of each polymorphic variation in the control population were as follows: AA = 95 (45.5%), AC = 91 (43.5%) and CC = 23 (11.0%). In the NSCLC subjects, the genotypic frequencies were as follows: AA = 131 (62.7%), AC = 73 (34.9%) and CC = 5 (2.4%). We detected statistically significant differences in the genotypic distribution between the NSCLC and the control subjects (p < 0.05, Pearson's chi-square test). The NSCLC risk correlated significantly with AA genotype. Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 2.45 (95% CI = 1.17-5.40) and that for the ones with AA genotype was 4.58 (95% CI = 2.17-10.30). These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Case-Control Studies
  • Female
  • Genotype
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / physiology
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Risk Factors


  • Insulin-Like Growth Factor Binding Protein 3