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Erschienen in:
01.03.2008 | Original Paper
TGFB1 and TGFBR2 functional polymorphisms and risk of esophageal squamous cell carcinoma: a case–control analysis in a Chinese population
Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2008
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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 < 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.