title: Promoter -202 A/C polymorphism of insulin-like growth factor binding protein-3 gene and non-small cell lung cancer risk.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Moon
authors.forename: Yoon Soo
authors.initials: YS
authors.lastname: Chang
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Ahn
authors.forename: Kyeong Nam
authors.initials: KN
authors.lastname: Yoo
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Shin
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kong
authors.forename: Young Sam
authors.initials: YS
authors.lastname: Kim
authors.forename: Joon
authors.initials: J
authors.lastname: Chang
authors.forename: Sung Kyu
authors.initials: SK
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Se Kyu
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000502:physiology; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3