Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy

Abstract

Background: The relationship between polymorphisms in vascular endothelial growth factor (VEGF) and gastric cancer is still inconclusive. We investigated whether there is an association between VEGF genetic polymorphisms and risk of gastric cancer, and evaluated the recurrence of advanced gastric cancer after curative resection with adjuvant chemotherapy according to VEGF genetic polymorphisms. Methods: The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene (+936C > T, - 634G > C, - 2578C > A, + 1612G > A) were evaluated. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A total of 151 patients with gastric cancer were enrolled, and the control group consisted of 413 individuals with esophago-gastroduodenoscopy who were randomly selected through health screening. All of the enrolled patients had curative resections with completion of adjuvant capecitabine and oxaliplatin combination chemotherapy and the initial metastatic cases were excluded. During the regular follow-up protocol, the episodes of the recurrence were documented and the specific genotype and allelic frequencies were evaluated. Results: As for the cancer risk, there were no significant differences in specific genotypes and allelic frequencies. The mean follow-up period was 28.82 ± 30.92 (12 ~ 72) months and the recurrence rate was 28.3%. In the patients carrying the 936-C allele, the recurrence rate of gastric cancer was high (P = 0.02). Disease-free interval was significantly different between the patients carrying the 936-CC and 936-CT/TT genotype (P = 0.02). Conclusions: VEGF 936-C allele is associated with poor prognosis, but not risk of gastric cancer. In the patients carrying the 936-C allele, more potent adjuvant treatment would be considered.