Single-nucleotide polymorphisms and haplotypes of vascular endothelial growth factor

Abstract

Vascular endothelial growth factor (VEGF) is one of the most predominant mediators of angiogenesis, plays a critical role in lung carcinogenesis. We performed a case–control study of 209 non-small cell lung cancer (NSCLC) patients and 189 sex, age and smoking matched healthy controls; genotyped 9 VEGF single-nucleotide polymorphisms (SNPs) in patients and controls selected from Kashmiri population and evaluated the NSCLC risk conferred by individual SNPs and haplotypes. In single-locus analysis, alleles of rs699947, rs833061, rs13207351, rs2010963 and rs3025021 showed association with NSCLC [P value=6.00e−04, 2.54e−11, 6.38e−09, 0.0082 and 0.0024]. However permutation test revealed association of only three markers (rs83306, rs13207351 and rs699947) with NSCLC [P value=0.000e0, 0.000e0 and 0.0086], Haplotype analysis of case-control subjects identified one block of two SNPs (rs3025020 and rs3025021) having linkage disequilibrium [D′=0.26]; NSCLC subjects formed two blocks of four SNPs in promoter, 5′-un-translated and intronic region (rs2010963, rs833061, rs13207351 and rs1413711) and four polymorphisms downstream of the coding sequence, in intron and 3′ un-translated region (rs2146323, rs3025020, rs3025021 and rs3025039) with highest linkage disequilibrium [D′=0.89] between rs13207351 and rs3025020. There were no significant differences in the tested single-nucleotide polymorphisms (SNPs) and haplotypes in patients with non-small cell lung cancer.