AIM: To identify a molecular marker for gastric cancer, andto investigate the relationship between the polymorphismof pepsinogen C (PGC) gene and the genetic predispositionto gastric cancer.METHODS: A total of 289 cases were involved in this study.115 cases came from Shenyang area, a low risk area ofgastric cancer, including 42 unrelated controls and 73 patientswith gastric cancer. 174 cases came from Zhuanghe area, ahigh-risk area of gastric cancer, including 113 unrelatedcontrols, and 61 cases from gastric cancer kindred families.The polymorphism of PGC gene was detected by polymerasechain reaction (PCR) and the relation between the geneticpolymorphism of PGC and gastric cancer was examined.RESULTS: Four alleles, 310bp (allele 1), 400bp (allele 2),450bp (allele 3), and 480bp (allele 4) were detected byPCR. The frequency of allele 1 was higher in patients withgastric cancer than that in controls. Genotypes containinghomogenous allele 1 were significantly more frequent inpatients with gastric cancerthan that in controls (0.33, 0.14,x2＝3.86, P＜0.05). There was no significant differencebetween the control group of Zhuanghe and the group ofgastric cancer kindred. But the frequency of allele 1 washigher in control group of Zhuanghe area than that in controlgroup of Shenyang area and genotypes containinghomogenous allele 1 were significantly more frequent inthe control group of Zhuanghe area than those in controlgroup of Shenyang area (0.33, 0.14, x2＝4.32, P＜0.05). Inthe group of gastric cancer kindred the frequency of allele 1was significantly higher than that in control group ofShenyang area (0.5164, 0.3571, x2＝4.47, P＜0.05).Genotypes containing homogenous allele 1 were significantlymore frequent in the group of gastric cancer kindred thanthose in control group of Shenyang area (0.36, 0.14, x2＝4.91,P＜0.05).CONCLUSION: These results suggest that there is somerelation between pepsinogen C gene polymorphism andgastric cancer, and the person with homogenous allele 1predisposes to gastric cancer than those with othergenotypes. Pepsinogen C gene polymorphism may be usedas a genetic marker for a genetic predisposition to gastriccancer. The distribution of pepsinogen C gene polymorphismin Zhuanghe, a high-risk area of gastric cancer, is differentfrom that in Shenyang, a low risk area of gastric cancer.