The proliferation of colorectal epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes can modify the colorectal cancer risk. TGF-[beta]1 can act as both a tumor suppressor and a stimulator of tumor progression. TGF-[beta]1 C-509T polymorphism in the promoter sequence has been associated with increased levels of plasma TGF-[beta]1 in individuals with T allele. To evaluate the potential influences of this polymorphism on colorectal adenoma and cancer risk, a case-control study was conducted in Korea. A total of 646 subjects were prospectively enrolled in Seoul National University Hospital. Risk of colorectal neoplasms was evaluated separately for 244 patients with colorectal adenoma, 152 patients with colorectal cancer relative to 250 healthy controls. Genotypes were determined by the PCR-RFLP method. ORs and 95% CIs were calculated by a multivariate logistic regression analysis. The TGF-[beta]1 -509T allele containing genotypes posed a reduced risk of colorectal cancer (adjusted OR = 0.59, 95% CI = 0.28-0.92). But there was no association between this polymorphism and colorectal adenoma. Our results suggest that the TGF-[beta]1 -509T allele may have a protective role in the development of colorectal cancer, possibly consistent with its role as an inhibitor of epithelial malignant transformation.