Vascular endothelial growth factor single-nucleotide polymorphism in gallbladder cancer

Abstract

Background and aim: Angiogenesis plays a key role in growth, progression, and metastasis of various cancers. Vascular endothelial growth factor (VEGF) polymorphism has been associated with several cancers. Role of VEGF has not been reported in gallbladder cancer (GBC). Present study was designed to investigate the role of VEGF polymorphism in GBC and in other (benign) gallbladder diseases, that is chronic cholecystitis (CC) and xanthogranulomatous cholecystitis (XGC).

Methods: Blood samples were collected from 195 GBC, 140 CC, and 47 XGC patients and 300 normal healthy controls. VEGF polymorphisms were investigated using amplification refractory mutation system polymerase chain reaction for g.43737830A>G and g.3437A>C, polymerase chain reaction-restriction fragment length polymorphism for c.*237C>T, and g.43736418delTinsG amplified by polymerase chain reaction.

Results: At g.43737830A>G, GA genotype showed susceptibility (odds ratio [OR] = 1.65 and OR = 1.68) and GG genotype showed protective association (OR = 0.58 and OR = 0.50) with GBC and CC. Allele A of VEGF g.43737830A>G was risk associated with GBC and CC (OR = 1.48 and OR = 1.70), while G allele was risk protective for GBC and CC (OR = 0.67 and OR = 0.58). At g.3437A>C, genotype CA was risk protective for GBC (OR = 0.61). TT genotype of c.*237C>T was susceptible for GBC and CC (OR = 2.59 and OR = 3.48), while CC genotype was risk protective for GBC and CC (OR = 0.61 and OR = 0.34). T allele of c.*237C>T polymorphism was risk associated with GBC and CC (OR = 1.63 and OR = 2.90), while C allele was risk protective for GBC and CC (OR = 0.38 and OR = 0.28). Haplotype I-C-A-C was risk protective for GBC (OR = 0.27).

Conclusion: The present study suggests that c.*237C>T and g.43737830A>G polymorphisms are useful markers of susceptibility to GBC.

Keywords: VEGF; chronic cholecystitis; gallbladder cancer; xanthogranulomatous cholecystitis.