Genetic variation in transforming growth factor-beta1 gene associated with increased risk of esophageal squamous cell carcinoma.

The genetic alterations leading to esophageal squamous cell carcinoma (ESCC) are gradually being discovered. A wide variety of genes have been associated with ESCC development as well as tumor progression. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine; it promotes tumor growth and metastasis in later stages of of cancer development. Variations in the DNA sequence in the TGF-beta1 gene may lead to altered TGF-beta1 production and/or activity, and so this can modulate an individual's susceptibility to ESCC. To test this hypothesis, we investigated the association of the TGF-beta1 gene -509 C/T and 869 T/C (Leu10Pro) polymorphisms and their haplotypes with the risk of ESCC. 247 patients with ESCC and 260 age- and sex-matched controls were studied using a polymerase chain reaction-restriction fragment length polymorphism. There were significant differences in the genotype and allele distribution of 869 T/C polymorphism of the TGF-beta1 gene among cases and controls. The 869 TC and CC genotypes were associated with a significantly increased risk of ESCC as compared with the 869 TT genotypes [odds ratio (OR) = 1.882, 95% confidence interval (CI) 1.212-2.923, P = 0.005 and OR = 2.099, 95% CI 1.288-3.421, P = 0.003, respectively]. Consistent with the results of the genotyping analyses, the -509 T/869 C haplotype was associated with a significantly increased risk of ESCC as compared with the -509 C/869 T haplotype (OR = 1.463; 95% CI 1.120-1.912; P = 0.005). This study shows for the first time that TGF-beta1 gene 869 T/C polymorphism may contribute to a genetic risk factor for ESCC in a Chinese population.