Influence of TGFB1 C-509T polymorphism on gastric cancer risk associated with TGF-β1 expression in the gastric mucosa.

Background: Transforming growth factor-β1 (TGF-β1) has dual roles inhibiting and promoting carcinogenesis. Although many researchers have conducted association studies between TGFB1 C-509T polymorphism and the risk of developing gastric cancer, the results are not uniform. Methods: We genotyped 1028 gastric cancer patients and 958 controls by the polymerase chain reaction-restriction fragment length polymorphism method. Immunohistochemistry was performed to assess the expression of TGF-β1 in the cancer and noncancerous tissues of 120 gastric cancer patients. mRNA expression was also measured in noncancerous gastric mucosa by qRT-PCR in the 282 subjects. Results: The CT genotype in the TGFB1 C-509T polymorphism was associated with an increased risk of gastric cancer development (adjusted OR 1.35, 95 % CI 1.07-1.71, P = 0.013), especially for intestinal-type cancer (adjusted OR 1.43, 95 % CI 1.08-1.90, P = 0.014). More frequent TGF-β1 expression was found in the center of cancer tissue in the TGFB1-509T carrier group than in the others (90.5 % vs. 72.2 %, P = 0.010). T-carriers also presented higher expression level of gastric TGF-β1 mRNA than non T-carriers (median 1.29 vs. 0.80, P = 0.004) when they were infected by H. pylori. Cancer patients showed elevated gastric TGFB1gene expression compared to the control group (median 1.22 vs. 0.89, P = 0.009). Conclusions: The carcinogenic effect of TGF-β1 might be associated with increased gastric TGF-β1 expression in subjects with the T allele of TGFB1-509. [ABSTRACT FROM AUTHOR]