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Moon, Chang, Han, Kang, Park, Byun, Chung, Park, Yoo, Shin, Kim, Chang, Kim, Kim, and Kim: Promoter -202 A/C Polymorphism of Insulin-like Growth Factor Binding Protein-3 Gene and Non-small Cell Lung Cancer Risk
Original Article

Tuberculosis and Respiratory Diseases 2005; 58(4): 359-366.

Published online: 30 April 2005

DOI: https://doi.org/10.4046/trd.2005.58.4.359

Promoter -202 A/C Polymorphism of Insulin-like Growth Factor Binding Protein-3 Gene and Non-small Cell Lung Cancer Risk

Jin Wook Moon, M.D.1, Yoon Soo Chang, M.D.1, Chang Hoon Han, M.D.1, Shin Myung Kang, M.D.1, Moo Suk Park, M.D.1, Min Kwang Byun, M.D.1, Wou Young Chung, M.D.1, Jae Jun Park, M.D.1, Kyeong Nam Yoo, M.D.2, 3, Ju Hye Shin, M.D.3, Young Sam Kim, M.D.1, 4, Joon Chang, M.D.1, 4, Sung Kyu Kim, M.D.1, 4, Hee Jung Kim, M.D.5, Se Kyu Kim, M.D.1, 2, 3, 4

1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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.

Address for correspondence: Se Kyu Kim, MD, PhD. Department of Internal Medicine, Yonsei University College of Medicine, C.P.O Box 8044, Seoul, Korea. 120-752. Phone: 82-2-2228-1954, Fax: 82-2-393-6884, sekyukim@yumc.yonsei.ac.kr.

Received 5 January 2005       Accepted 15 March 2005

Copyright©2005. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

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 interindividual 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 polymorphic 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 frequencies 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.

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)

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