Association of VEGFR1, VEGFR2 and VEGFR3 polymorphisms with esophageal cancer risk: a case–control study

Abstract Background Esophageal cancer is the eleventh most common cancer and is the seventh leading cause of mortality worldwide. Vascular endothelial growth factor (VEGF) and its receptors pathway are a key regulator of angiogenesis and play an important role in carcinogenesis. The aim of current study was to evaluate the association of five VEGFR polymorphisms with esophageal cancer risk in patients from Punjab, North-west India. Methods This case–control study included 310 esophageal cancer patients and 325 age and gender matched healthy controls. VEGFR1 -710C/T, VEGFR2 -604 T/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. Restriction digestion products were analyzed on 2.4% agarose gel and genotype was assigned to each sample on the basis of fragments obtained after digestion. Randomly 10% samples were repeated by Sanger sequencing to revalidate the results. Results 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 -604 T/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 A 1719 A 1192 was significantly associated with the decreased esophageal cancer risk (OR = 0.44; 95%CI, 0.23–0.84; p = 0.01). Conclusion VEGFR1 -710C/T , VEGFR2 -604 T/C and VEGFR2 1192G/A polymorphisms were associated with the decreased risk of esophageal cancer in patients from Punjab, North-west India. Graphical abstract