Tuberc Respir Dis.
2005 Apr;58(4):359-366.
Promoter -202 A/C Polymorphism of Insulin-like Growth Factor Binding Protein-3 Gene and Non-small Cell Lung Cancer Risk
- Affiliations
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- 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. sekyukim@yumc.yonsei.ac.kr.
- 2Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
- 3Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea.
- 4The Institute of Chest Diseases, Yonsei University College of Medicine, Seoul, Korea.
- 5Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.
Abstract
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BACKGROUND: IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of 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 its degradation. More than half of the inter- individual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene.
METHOD: We attempted to ascertain whether A-202C poly?morphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects.
RESULT: In the 104 NSCLC subjects, the genotypic freque?ncies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16).
CONCLUSION
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.
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