Journal
HUMAN GENETICS
Volume 132, Issue 6, Pages 641-648Publisher
SPRINGER
DOI: 10.1007/s00439-013-1275-6
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Funding
- National Natural Science Foundation of China [30901360, 81270031, 30930085]
- 973 project [2013CB530501]
- Natural Science Foundation of the Higher Education Institutions of Jiangsu Province [12KJB320012]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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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 x 10(-8)). Compared with CC homozygotes, GG homozygotes and G allele carriers showed 3.73-fold (P = 2.98 x 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.
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