Abstract: OBJECTIVE: To investigate the possible association of the transforming growth factor β1(TGF-β1) gene T869C, G915C and C788T polymorphisms with susceptibility to gastric cardia adenocarcinoma(GCA) in a population of North China. METHODS: Polymerase-chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to detect the genotype of T869C, G915C and C788T single nucleotide polymorphisms(SNPs) in 214 GCA patients and 298 healthy controls. The level of TGF-β1 was measured by ELISA and the protein expression of TGF-β1 in tumors and corresponding normal tissues was detected by immunohistochemistry method. RESULTS: The overall genotype and allelotype distributions of TGF-β1 T869C polymorphism in GCA patients were significantly different from that in healthy controls(P<0.05). The frequency of C allelotype was significantly higher in GCA patients than that in healthy controls (55.8％ vs.45.8％, P<0.01), the C allelotype significantly increased the risk of developing GCA [adjusted odds ratio (OR)=1.50, 95％ confidence interval(CI)=1.17－2.11]. Compared with TT genotype, the TC and CC genotypes significantly enhanced the risk of developing GCA(adjusted OR=1.91 and 2.18, respectively; 95％CI=1.34－2.41 and 1.56－2.71, respectively). The genotype and allelotype distributions of TGF-β1 G915C and C788T polymorphism in GCApatients were not significantly different from that in healthy controls(P>0.05). The level of TGF-β1 was higher in GCA patients than that in healthy controls(P<0.01) and GCA patients with C allelotype of T869C site were higher than that without C allelotype(P<0.05). The protein expression of TGF-β1 in GCA tumor tissues(65.5％) was significantly higher than that in corresponding normal tissues (15.5％)(P<0.01) and GCA patients with C allelotype of T869C site were higher than that without C allelotype(P<0.05). CONCLUSION: C allelotype of TGF-β1 T869C may be one of the factors that affects the risk of developing GCA in north China and C allelotype carriers may be at increased risk of GCA by enhancing the TGF-β1 expression.

Key words: transforming growth factor β1, polymorphism, gastric cardia adenocarcinoma, susceptibility