title: Polymorphisms of transforming growth factor-β1 associated with increased risk of gastric cardia adenocarcinoma in north China.
abstract: 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.
authors.affiliation: Laboratory of Pathology Research Center, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Jiankanglu 12, Shijiazhuang, Hebei, China.
authors.forename: W
authors.initials: W
authors.lastname: Guo
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Kuang
authors.forename: B
authors.initials: B
authors.lastname: Shan
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000368:Aged; D000483:Alleles; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002299:Cardia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1