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

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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.

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