Kaur Ravinder, Nagpal Jatin K, Das Bibhu R
Research and Development Division, SRL-Ranbaxy Ltd., Clinical Reference Laboratories, Mumbai, India.
Tumour Biol. 2005 May-Jun;26(3):147-52. doi: 10.1159/000086486. Epub 2005 Jun 20.
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.
胰岛素和胰岛素样生长因子（IGFs）是细胞增殖和凋亡的主要决定因素，因此在肿瘤发生过程中发挥着重要作用。流行病学证据表明，高水平的胰岛素和胰岛素样生长因子与癌症风险增加有关。胰岛素信号通路相关基因的多态性与不同种族和环境背景下肿瘤发生的风险差异有关。在本研究中，我们采用基于聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的分析方法，调查了印度裔咀嚼烟草介导的口腔癌患者（n = 60）和健康对照者（n = 45）中胰岛素（INS）基因和胰岛素样生长因子2（IGF-2）基因的遗传多态性分布。对INS基因的+1127 INS-Pst1位点和IGF-2基因的+3580 IGF-2-Msp1位点进行基因分型。在口腔癌患者中发现的IGF-2基因AG、GG和AA基因型频率分别为0.68、0.2和0.12，而在非癌症对照者中这些频率分别为0.27、0.71和0.02。INS基因各等位基因（即CT、TT和CC）的频率在肿瘤人群（0.22、0.75和0.03）和正常人群（0.27、0.67和0.06）中几乎相等。与白种人、非洲人和西班牙裔人群相比，印度裔人群中IGF-2和INS基因的基因型频率存在显著差异。INS基因+1127 INS-Pst1位点的多态性与口腔癌无关，而IGF-2基因+3580 IGF-2-Msp1位点的AG或AA基因型与口腔癌的进展和风险增加有关。从我们的研究可以得出结论，IGF-2基因中的单核苷酸多态性可作为预测口腔癌发生风险的标志物。
