Association analysis of genetic variants in microRNA networks and gastric cancer risk in a Chinese Han population
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To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer.
We genotyped 19 SNPs of the microRNA-related genes in a case–control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population.
We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p = 0.033, aOR = 0.742, 95%CI = 0.564–0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p = 0.037, aOR = 0.771, 95%CI = 0.604–0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p = 0.021, aOR = 0.529, 95%CI = 0.307–0.910) and TMN stage (p = 0.021, aOR = 0.532, 95%CI = 0.311–0.908), respectively.
Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population.
KeywordsMicroRNA Gastric cancer Single-nucleotide polymorphism
- Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353(17):1793–1801. doi: 10.1056/NEJMoa050995 PubMedCrossRefGoogle Scholar
- Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, Fredrickson T, Landgraf P, Ramachandra S, Huppi K, Toro JR, Zenger VE, Metcalf RA, Marti GE (2007) Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood 109(12):5079–5086. doi: 10.1182/blood-2007-02-071225 PubMedCrossRefGoogle Scholar
- Reshmi G, Surya R, Jissa VT, Babu PS, Preethi NR, Santhi WS, Jayaprakash PG, Pillai MR (2011) C-T variant in a miRNA target site of BCL2 is associated with increased risk of human papilloma virus related cervical cancer-An in silico approach. Genomics 98(3):189–193. doi: 10.1016/j.ygeno.2011.06.005 PubMedCrossRefGoogle Scholar
- Saetrom P, Biesinger J, Li SM, Smith D, Thomas LF, Majzoub K, Rivas GE, Alluin J, Rossi JJ, Krontiris TG, Weitzel J, Daly MB, Benson AB, Kirkwood JM, O’Dwyer PJ, Sutphen R, Stewart JA, Johnson D, Larson GP (2009) A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res 69(18):7459–7465. doi: 10.1158/0008-5472.CAN-09-1201 PubMedCrossRefGoogle Scholar
- Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R, Ma H, Chen Y, Shen H (2009) A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev 18(4):1183–1187. doi: 10.1158/1055-9965.EPI-08-0814 PubMedCrossRefGoogle Scholar
- Yang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K (2009) IFN regulatory factor 8 sensitizes soft tissue sarcoma cells to death receptor-initiated apoptosis via repression of FLICE-like protein expression. Cancer Res 69(3):1080–1088. doi: 10.1158/0008-5472.CAN-08-2520 PubMedCrossRefGoogle Scholar