Association of VEGFR1, VEGFR2 and VEGFR3 Polymorphisms with Esophageal Cancer Risk: A Case- Control Study

Abstract

Abstract Esophageal cancer is the eighth most common cancer with 5.3% cancer related deaths worldwide. Vascular endothelial growth factor (VEGF) and its receptors pathway is a key regulator of angiogenesis and play an important role in carcinogenesis. The aim of current study was to evaluate the association of five VEGFRs polymorphisms with esophageal cancer risk in patients from Punjab, North-West India. This case-control study included 310 esophageal cancer patients and 325 age and gender matched healthy controls. VEGFR1 -710C/T, VEGFR2 -604T/C (rs2071559), VEGFR2 1192 G/A (rs2305948), VEGFR2 1719A/T (rs1870377) and VEGFR3 (rs72816988) polymorphisms were genotyped by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. There was a significant association of CT genotype (OR = 0.28; 95%CI, 0.10–0.76; p = 0.01) and T allele (OR = 0.28; 95%CI, 0.10–0.77; p = 0.01) of VEGFR1-710C/T polymorphism with decreased risk of esophageal cancer. TC genotype of VEGFR2 -604T/C (OR = 0.66; 95%CI, 0.44–0.97; p = 0.03) and GA genotype of VEGFR2 1192G/A (OR = 0.54; 95%CI, 0.31–0.95; p = 0.03) polymorphisms were significantly associated with decreased risk of esophageal cancer. There was no significant difference in allele and genotype frequency of VEGFR2 1719A/T and VEGFR3 (rs72816988) polymorphisms between esophageal cancer patients and controls (p > 0.05). Haplotype analysis revealed that haplotype C-604 A1719A1192 was significantly associated with the decreased esophageal cancer risk (OR = 0.44; 95%CI, 0.23–0.84; p = 0.01). In conclusion, VEGFR1 -710C/T, VEGFR2 -604T/C and VEGFR2 1192G/A polymorphisms were associated with the decreased risk of esophageal cancer in patients from Punjab, North-West India.