VEGF Polymorphisms in Gall Bladder Cancer

Abstract

Purpose: Gall bladder cancer (GBC) is common in Chile and in north India. Angiogenesis plays an important role in carcinogenesis. Vascular endothelial growth factors (VEGF) at 6p12 play an important role in carcinogenesis. VEGF overexpression has been found in many cancers. We studied VEGF single nucleotide polymorphisms (SNPs) in GBC and gall stone associated benign diseases viz. chronic cholecystitis (CC) and xantho-granulomatous cholecystitis (XGC). Methods: DNA was extracted from blood in patients with GBC (n=195), CC (n=140), XGC (n=47), and normal controls (n=300). VEGF polymorphism (-1154G/A, -2578C/A, +936C/T and 18 bp -2549I/D) was investigated using PCR-RFLP method. Results: -1154G/A heterozygous genotype GA and +936C/T genotype TT were risk associated with GBC (OR 1.65, p=0.01; OR 2.59, p=0.02) and CC (OR 1.68, p=0.01; OR 3.48, p=0.003). -2578C/A heterozygous genotype CA was protective for GBC (OR=0.6, p=0.01). Combitorial analysis revealed that ICGC, DTGC, DCAC, and DTGA were predisposing haplotypes for GBC, CC, and XGC. Haplotype DTGA, containing mutant alleles, showed highest risk for GBC (OR 15.15, p<0.0001), CC (OR 7.5, p=0.007), and XGC (OR 10.6, p=0.001). Haplotype DCGC was risk protective for GBC (OR 0.28, p<0.0001), CC (OR 0.39, p<0.0001), and XGC (OR 0.32, p=0.001). Haplotype ICAC was protective for GBC (OR 0.27, p=0.0001). Conclusion: Hsing et al (2008) also found VEGF polymorphism to be associated with GBC. VEGF polymorphism may play a role in carcinogenesis of GBC and needs further evaluation.