Association of vascular endothelial growth factor gene polymorphisms with esophageal squamous cell cancer risk in North-West Indians: A case-control study

Vascular endothelial growth factor (VEGF) is a crucial regulator of physiological and pathological angiogenesis. Increased VEGF expression has been linked with inappropriate VEGF-induced angiogenesis in various disease pathologies including cancers. The aim of present study was to investigate the role of seven VEGF promoter polymorphisms [-417T/C (rs833062), -172C/A (rs59260042), -165C/T (rs79469752), -160C/T, -152G/A (rs13207351), -141A/C (rs28357093), and -116G/A (rs1570360) with esophageal squamous cell cancer risk in North-West Indians.

In this case-control study, DNA samples of 199 esophageal squamous cell cancer (ESCC) patients and 210 healthy controls from Punjab, North-West India were screened for VEGF -417T/C, -172C/A, -165C/T, -160C/T, -152G/A, -141A/C and -116G/A promoter polymorphisms using Sanger sequencing.

The mean age of patients and controls was 56.16±12.98 and 54.06 ±11.99 years respectively. In 62.81% of patients, cancer was diagnosed after the age of 50 years. The number of female patients was higher as compared to male patients. Of the 199 ESCC patients, 25 (12.56%) had stage I, 89 (44.72%) had stage II, 51 (25.63%) had stage III, and 18 (9.05%) had stage IV tumor. AA genotype and A allele of both VEGF -152G/A and -116G/A polymorphisms were significantly associated with elevated risk to ESCC in total subjects as well as in female group. CT genotype and T allele of VEGF-165C/T polymorphism was significantly associated with reduced risk for ESCC only in female group. Linkage disequilibrium was observed between VEGF -165C/T and VEGF -141A/C (D′ = 0.85, r2 = 0.73) and between VEGF-152G/A and VEGF -116G/A (D′ = 0.93, r2 = 0.50) polymorphisms. Haplotype T-C-C-C-A-A-A was significantly associated with increased ESCC risk in total subjects as well as in female group.

From this study we concluded that VEGF-116 G/A and VEGF-152G/A polymorphisms were significantly associated with increased ESCC risk in total patients as well as in female group whereas VEGF -165 C/T polymorphism was associated with reduced risk only in female group. Identification of correlation between VEGF polymorphisms and their haplotypes with particular therapy may be helpful in better selection of patients for treatment.

The authors.

MHRD grant under RUSA 2.0 scheme.

All authors have declared no conflicts of interest.