Purpose: Transforming growth factor beta1 (TGF-beta1) and its receptor II (TGF-betaRII) are two key components of TGF-beta 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-beta1 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 (chi (trend) (2) = 33.87, P < 0.001) compared with subjects with both wild-type genotypes.
Conclusions: These results are consistent with our previous findings in gastric cancer and support the hypothesis that genetic variants in TGFB1 and TGFBR2 may modulate the risk of ESCC.
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