title: A miR-570 binding site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma.
abstract: Single nucleotide polymorphisms (SNPs) in putative microRNA (miRNA) target sites (miRSNPs) could affect the binding of miRNA with the target and contribute to the susceptibility of human cancers. However, the role of miRSNPs in gastric cancer susceptibility remains largely unknown. Since the over-expression of B7-H1 protein has been reported to be closely related to disease progression of gastric cancer, we investigated the possible role of miRSNPs at the 3'-untranslated region (3'-UTR) of B7-H1 in the risk of developing gastric cancer. In this association study on 205 gastric adenocarcinoma patients and 393 non-cancer controls, we found that the genotype distribution of a common C>G polymorphism (rs4143815) was significantly different between the cases and controls (P = 1.32 × 10(-8)). Compared with CC homozygotes, GG homozygotes and G allele carriers showed 3.73-fold (P = 2.98 × 10(-8)) and 1.85-fold (P = 0.002) increased risk of gastric adenocarcinoma, respectively. Stratified analyses indicated that variant genotypes had a strong association with the clinic-pathological features of gastric cancer including differentiation grade, depth of tumor infiltration, and tumor node metastasis (TNM) stage (P < 0.001). Luciferase reporter assay indicated that this SNP might be responsible for aberrant B7-H1 protein expression in gastric cancer by disrupting the interaction between miR-570 and B7-H1 mRNA. These results are consistent with our hypothesis and indicate that genetic polymorphisms influencing B7-H1 expression modify cancer susceptibility.
authors: Stem Cell Research Laboratory of Jiangsu Province and Jiangsu Institute of Clinical Immunology, Soochow University, Suzhou, 215007, Jiangsu, People's Republic of China.
authors: Weipeng
authors: W
authors: Wang
authors: Fang
authors: F
authors: Li
authors: Yong
authors: Y
authors: Mao
authors: Huan
authors: H
authors: Zhou
authors: Jing
authors: J
authors: Sun
authors: Rui
authors: R
authors: Li
authors: Cuiping
authors: C
authors: Liu
authors: Weichang
authors: W
authors: Chen
authors: Dong
authors: D
authors: Hua
authors: Xueguang
authors: X
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics*; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C582115:MIRN570 microRNA, human; D035683:MicroRNAs