Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits the mitogenic and anti-apoptotic 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 inter-individual 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. After extracting the genomic DNA, we amplified the 168-base-pair (bp) fragment encompassing the A-202C polymorphic site in IGFBP-3 gene. Each PCR product was digested with FspI enzyme and electrophoresed. The allele was designated either C or A depending on whether the FspI restriction site was present or not.
The frequencies of each polymorphic variation in the control population were as followes: 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 χ2 –test). The NSCLC risk correlated significantly with AA genotype. Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.45 (95% CI: 1.17 - 5.40) and the OR for the ones with AA genotype was 4.58 (95% CI: 2.17 - 10.30).
Our results indicate that there are differences in the genotypic distribution at the A-202C polymorphic site of IGFBP-3 gene between NSCLC and general populations.
The dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, a potential target for novel antineoplastic therapies, and preventative strategies in high-risk groups.
Jin Wook Moon, None.