TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case–control analysis in a Chinese population

Purpose Transforming growth factor β1 (TGF-β1) and its receptor II (TGF-βRII) are two key components of TGF-β signaling and play an important role in carcinogenesis. Several functional polymorphisms were identified in TGFB1 and TGFBR2 and associated with elevated serum or plasma level of TGF-β1 and enhanced transcription activity of TGFBR2 . This population-based case–control study was to evaluate the contribution of functional polymorphisms in TGFB1 C-509T, Leu10Pro and TGFBR2 G-875A to the risk of esophageal squamous cell carcinoma (ESCC). Methods Genotyping was performed using the primer-introduced restriction analysis-PCR assay in 255 ESCC cases and 704 cancer-free controls in a Chinese population. Results The variant genotypes (-509CT/TT) of TGFB1 C-509T were associated with a 63% significantly decreased risk of ESCC (adjusted OR = 0.37, 95% CI = 0.27–0.50) compared with -509CC wild-type homozygote. In addition, a moderately decreased risk of ESCC was related to -875GA (adjusted OR = 0.70, 95% CI = 0.49–0.99) but not -875AA genotype (adjusted OR = 1.09, 95% CI = 0.51–2.35) in TGFBR2 , compared with -875GG common genotype. Furthermore, subjects carrying variant genotypes either or both of TGFB1 C-509T and TGFBR2 G-875A had a significantly reduced risk of ESCC (adjusted OR = 0.37, 95% CI = 0.26–0.53 for either one variant genotype and adjusted OR = 0.30, 95% CI = 0.19–0.48 for both variant genotypes) in a dose-response manner (χ trend 2 = 33.87, P