Polymorphism in IGF-2 as a surrogate marker for predisposition towards tobacco chewing-mediated oral cancer

Insulin and insulin-like growth factors (IGFs) are major determinants of proliferation and apoptosis, thereby playing a significant role in carcinogenesis. Epidemiological evidence associates high levels of INS and IGFs with an increased risk of cancer. Polymorphism of the genes involved in insulin-signaling pathways has been associated with a variable risk for neoplasms in different ethnic and environmental backgrounds. In this study, using PCR-RFLP-based assays, we investigated the distribution of genetic polymorphism in INS and IGF-2 genes in tobacco chewing-mediated oral cancer patients (n = 60) and healthy controls ( n = 45) of Indian ethnic origin. The genotyping was performed for + 1127 INS-Pst1 in INS and + 3580 IGF-2-Msp1 in IGF-2. The frequencies of the IGF-2 genotypes AG, GG and AA found in oral cancer patients were 0.68, 0.2 and 0.12, respectively, whereas in noncancer controls these frequencies were 0.27, 0.71 and 0.02. Frequencies of each allele, i.e. CT, TT and CC of INS gene, were found to be nearly equal in the tumor (0.22, 0.75 and 0.03) as well as the normal ( 0.27, 0.67 and 0.06) population. A significant difference was observed in genotypic frequencies of IGF-2 and INS in the Indian ethnic population as compared to the Caucasian, African and Hispanic populations. Polymorphism at + 1127 INS-Pst1 locus of INS gene does not show an implication in oral cancer, whereas the genotype AG or AA at + 3580 IGF-2-Msp1 locus of IGF-2 is associated with progression and increased risk of oral cancer. From our study we can conclude that single nucleotide polymorphisms in the IGF-2 gene can be used as a marker for prediction of the risk of oral carcinogenesis. Copyright (C) 2005 S. Karger AG, Basel.