Abstract
Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1 expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.
Highlights
Gastric cancer (GC) is the fifth most commonly occurring cancer and third leading cause of cancer mortality in the world (McLean and El-Omar, 2014)
Single nucleotide polymorphism in Insulin-like growth factors-1 (IGF-1) regulatory elements may lead to alter in IGF-1expression level and GC susceptibility
In order to find potential predisposing risk factors of GC, we selected an important polymorphism of IGF-1 gene and investigated whether the rs5742612 variant could have an effect on susceptibility and progression of GC risk in an Iranian population
Summary
Gastric cancer (GC) is the fifth most commonly occurring cancer and third leading cause of cancer mortality in the world (McLean and El-Omar, 2014). Among the some genetic changes, there is evidence that the upregulation of certain growth factors could play a significant role in the development and progression of gastric cancer (Altinkaynak et al, 2012). Insulin-like growth factors-1 (IGF-1) is one of the significant growth factors It is multifunctional peptide, affecting cell proliferation in almost every cell type through the RAS, RAF-MAP kinase signaling pathway and has antiapoptotic influence via activation of the phosphatidylinositol-3 kinase-AKT pathway, which use activates downstream transcription factors that mediate gene expression of proliferation, differentiation, and antiapoptotic agents (Karamouzis and Papavassiliou, 2006; Samani et al, 2007; Tao et al, 2007; Pollak 2008; Yang et al, 2014).
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