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 (P>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 (P<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.
© 2011 Blackwell Publishing Ltd.