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The relationship between gastric cancer and serum vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2, which are soluble form receptor proteins of vascular endothelial growth factor (VEGF), has not been extensively studied. VEGF, sVEGFR-1 and sVEGFR-2 were measured in the sera obtained before surgical operation from 164 gastric cancer patients and from 164 healthy controls matched for age and gender. Compared with controls, the cases showed elevated VEGF (< 0.01) and reduced sVEGFR-1 (= 0.07) and sVEGFR-2 (= 0.02). The difference in VEGF levels was small among men and when the outcome was early cancer. The difference in sVEGFR-1 levels was significant or borderline significant only in men and when the outcome was diffuse type cancer. The difference in sVEGFR-2 levels was significant only in men and when the outcome was advanced or diffuse type cancer. The sensitivities and specificities of VEGF, sVEGFR-1 and sVEGFR-2 were all approximately 60%. For diffuse type cancer, sVEGFR-2 showed a sensitivity of 62.4% and a specificity of 63.4%, which was similar to serum pepsinogen. In conclusion, elevated VEGF and reduced sVEGFR-1 and sVEGFR-2 in serum are characteristic of gastric cancer patients, and the value of serum sVEGFR-2 in the diagnosis of diffuse type gastric cancer should be further evaluated. (Cancer Sci 2011; 102: 866–869)