Polymorphisms of transforming growth factor-β1 associated with increased risk of gastric cardia adenocarcinoma in north China

Authors


  • Supported by grants from the important medical subjects foundation of Hebei province.

Baoen Shan, Hebei Cancer Institute, the fourth hospital of Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, Hebei, China. Tel: +86 311 86095337; Fax: +86 311 86077634; E-mail: baoenshan2008@yahoo.cn

Summary

Transforming growth factor beta 1 (TGF-β1) is a multifunctional cytokine that has been implicated in the oncogenesis and tumour progression. However, the association of TGF-β1 polymorphism with gastric cardia adenocarcinoma (GCA) remains unclear. The aim of the study was to investigate the possible association of the polymorphisms of TGF-β1 with susceptibility to GCA in a population of north China. A case–control analysis was performed to assess the association of six single nucleotide polymorphisms (SNPs) of TGF-β1 and GCA risk. The genotype and allele distributions of TGF-β1 G−800A, C−988A, G915C and C788T in GCA patients were not significantly different from that in healthy controls (> 0.05). The −509T and 869C allele significantly elevated the risk of developing GCA (adjusted OR = 1.45 and 1.41; 95% CI = 1.04–2.10 and 1.07–2.08, respectively). The CT and TT genotype of C−509T and the TC and CC genotype of T869C significantly elevated the risk of developing GCA. When stratified by tumour stage, the −509T and 869C allele carriers had an increased risk of TNM stage III + IV GCA as compared with noncarriers. The C−509T and T869C SNP are in a strong linkage disequilibrium (D′ = 0.94). Compared with C/T haplotype, T/C haplotype significantly increased the risk of developing GCA. The TGF-β1 level and expression were higher in GCA patients with −509T or 869C allele than in those without T or C allele (< 0.05). GCA patients with −509TT and 869CC genotype had higher apoptotic tumour-infiltrating lymphocytes in their cancer tissues than those with −509CC and 869TT genotype. In all, TGF-β1 C−509T and T869C polymorphisms may be associated with an increased risk of GCA in north China.

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