Promoter -202 A/C Polymorphism of Insulin-like Growth Factor Binding Protein-3 Gene and Non-small Cell Lung Cancer Risk.
10.4046/trd.2005.58.4.359
- Author:
Jin Wook MOON
1
;
Yoon Soo CHANG
;
Chang Hoon HAN
;
Shin Myung KANG
;
Moo Suk PARK
;
Min Kwang BYUN
;
Wou Young CHUNG
;
Jae Jun PARK
;
Kyeong Nam YOO
;
Ju Hye SHIN
;
Young Sam KIM
;
Joon CHANG
;
Sung Kyu KIM
;
Hee Jung KIM
;
Se Kyu KIM
Author Information
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. sekyukim@yumc.yonsei.ac.kr.
- Publication Type:Original Article
- Keywords:
Insulin-like growth factor (IGF);
Insulin-like growth factor binding protein-3 (IGFBP-3);
Non-small cell lung cancer (NSCLC);
Promoter -202 A/C polymorphism;
Restriction fragment length polymorphism (RFLP)
- MeSH:
Axis, Cervical Vertebra;
Carcinoma, Non-Small-Cell Lung*;
Genotype;
Humans;
Insulin-Like Growth Factor Binding Protein 3;
Odds Ratio;
Risk Factors;
Smoke;
Smoking
- From:Tuberculosis and Respiratory Diseases
2005;58(4):359-366
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.