Effect of polymorphisms in the 3′ untranslated region (3′-UTR) of vascular endothelial growth factor gene on gastric cancer and peptic ulcer diseases in Japan

A complex interaction of host genetic and environmental factors may be relevant in the development of Helicocobacter pylori-related gastric carcinogenesis. We investigated the effect of vascular endothelial growth factor (VEGF) gene polymorphisms on the risk of gastric cancer (GC) and peptic ulcer diseases in a Japanese population. The G1612A-(rs10434) and C936T(rs3025039) polymorphisms in the 3′ untranslated region (3′-UTR) of VEGF gene were genotyped in a total of 844 subjects including 385 GC, 143 ulcer including 98 gastric ulcer (GU), 45 duodenal ulcer (DU), and 316 nonulcer subjects. The 1612A carrier held a significantly higher risk of GC when compared to both noncancer and nonulcer (overall noncancer vs. GC; OR=1.61, 95% CI=1.17-2.21, P=0.0038, nonulcer vs. GC; OR=1.54, 95% CI=1.07-2.22, P=0.0197). The 1612A carrier was more closely associated with an increased risk of noncardiac cancer (OR=1.64, 95% CI=0.17-2.21, P=0.0038), lower third cancer (OR=1.97, 95% CI=1.30-3.00, P=0.002), and Lauren's diffuse-type cancer (OR=1.75, 95% CI=1.24-2.46, P=0.001), while the same genotype was not associated with the progression of GC. The C936T genotype was not associated with a risk of GC and its progression. Both the G1612A and C936T genotypes were not associated with the risk of peptic ulcer diseases. Our data suggest that the G1612A, but not C936T polymorphisms in the 30-UTR of VEGF gene is associated with the susceptibility to GC in the Japanese population.