Transforming growth factor-beta 1 (TGF-beta1) inhibits the proliferation of tumors in early stages of cancers, whereas it promotes tumor growth and metastasis in later stages of cancers. To examine the effect of the TGF-beta1 polymorphisms on gastric cancer risk, we studied the association between C-509T and T+29C (Leu10Pro) polymorphisms in TGF-beta1 and gastric cancer risk in 414 cases and 414 controls in the Chinese population. When the overall gastric cancer cases were compared with the controls, no significant difference was found in genotype distributions for both the polymorphisms examined. However, when stratified by tumor stage, the -509T and +29C allele carriers had a 0.57-fold (95% CI = 0.36-0.90) and a 0.58-fold (95% CI = 0.36-0.91) decreased risk of TNM stage I+II gastric cancer, respectively, as compared with non-carriers. We conclude that TGF-beta1-509T and +29C alleles may have a protective role in the development of stage I+II gastric cancer.