Esophageal cancer is one of the most aggressive cancers in the world, 70 % of which are from China and esophageal squamous cell carcinoma (ESCC) is the major histopathological form (>90 %). The single nucleotide polymorphisms (SNPs) in mature sequence of microRNA (miRNA) (mmSNPs) could cause the alteration of microRNA expression and contribute to the susceptibility of cancers. To evaluate the association between mmSNPs and ESCC, a case-control study including 773 patients with ESCC and 882 gender- and age-matched controls was carried out to investigate the association of five mmSNPs (miR-449b rs10061133, miR-4293 rs12220909, miR-608 rs4919510, miR-627 rs2620381, and miR-646 rs6513497) with ESCC susceptibility. As a result, two SNPs, miR-449b rs10061133 and miR-4293 rs12220909, were associated with decreased ESCC risk. For miR-449b rs10061133 A>G, individuals carrying GG genotype had an odds ratio (OR) of 0.77 (95 % confidence interval (95 % CI) 0.62–0.97) compared with individuals with AA genotype. In the recessive model, the GG genotype also showed a protective effect on ESCC (OR = 0.78, 95 % CI 0.63–0.97). For miR-4293 rs12220909 G>C, the heterozygous genotype GC was associated with a decreased ESCC risk (OR = 0.77, 95 % CI 0.61–0.97) compared with GG genotype. The C allele conferred 23 % decrease in ESCC risk compared with the G allele in the allelic model (95 % CI 0.63–0.93). In the dominant model, the GC/CC genotypes decreased the risk of ESCC (adjusted OR = 0.77, 95 % CI 0.61–0.96). This study provides the first evidence that miR-449b rs10061133 and miR-4293 rs12220909 are associated with ESCC risk in Chinese population.
This is a preview of subscription content, log in to check access.
This work was supported by the grants from the National Natural Science Foundation of China (grant numbers 81071957), the Key Project in the National Science & Technology Pillar Program (grant number 2011BAI09B00), the Suzhou City Science and Technology Program (grant number SYS201419), the Priority Academic Program Development of Jiangsu Higher Education Institutions of China (PAPD), and the funds from “China’s Thousand Talents Program” at Fudan University.
Vizcaino AP, Moreno V, Lambert R, Parkin DM. Time trends incidence of both major histologic types of esophageal carcinomas in selected countries, 1973–1995. Int J Cancer. 2002;99(6):860–8. doi:10.1002/ijc.10427.CrossRefPubMedGoogle Scholar
Zhang Y, Dai J, Deng H, Wan H, Liu M, Wang J, et al. miR-1228 promotes the proliferation and metastasis of hepatoma cells through a p53 forward feedback loop. Br J Cancer. 2014. doi:10.1038/bjc.2014.593.Google Scholar
Wei WJ, Wang YL, Li DS, Wang Y, Wang XF, Zhu YX, et al. Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population. Endocrine. 2014. doi:10.1007/s12020-014-0467-8.Google Scholar
Wang R, Zhang J, Jiang W, Ma Y, Li W, Jin B, et al. Association between a variant in microRNA-646 and the susceptibility to hepatocellular carcinoma in a large-scale population. Sci World J. 2014;2014:312704. doi:10.1155/2014/312704.Google Scholar
Gong J, Tong Y, Zhang HM, Wang K, Hu T, Shan G, et al. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum Mutat. 2012;33(1):254–63. doi:10.1002/humu.21641.CrossRefPubMedGoogle Scholar
Fang Y, Gu X, Li Z, Xiang J, Chen Z. miR-449b inhibits the proliferation of SW1116 colon cancer stem cells through downregulation of CCND1 and E2F3 expression. Oncol Rep. 2013;30(1):399–406. doi:10.3892/or.2013.2465.PubMedGoogle Scholar
Ma L, Li N, He X, Zhang Q. miR-449b and miR-34c on inducing down-regulation of cell cycle-related proteins and cycle arrests in SKOV3-ipl cell, an ovarian cancer cell line. J Peking Univ Health Sci. 2011;43(1):129–33.Google Scholar
Weng W, Yin J, Zhang Y, Qiu J, Wang X. Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin. Int J Oncol. 2014;44(3):812–8. doi:10.3892/ijo.2014.2253.PubMedGoogle Scholar
Hu YC, Lam KY, Law S, Wong J, Srivastava G. Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC. Clin Cancer Res. 2001;7(11):3519–25.PubMedGoogle Scholar
Li H, Xiao W, Ma J, Zhang Y, Li R, Ye J, et al. Dual high expression of STAT3 and cyclinD1 is associated with poor prognosis after curative resection of esophageal squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7(11):7989–98.PubMedPubMedCentralGoogle Scholar
Yang X, Feng M, Jiang X, Wu Z, Li Z, Aau M, et al. miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev. 2009;23(20):2388–93. doi:10.1101/gad.1819009.CrossRefPubMedPubMedCentralGoogle Scholar
Xu J, Hu Z, Xu Z, Gu H, Yi L, Cao H, et al. Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population. Hum Mutat. 2009;30(8):1231–6. doi:10.1002/humu.21044.CrossRefPubMedGoogle Scholar
Zhu W, You Z, Li T, Yu C, Tao G, Hu M, et al. Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas. Jpn J Clin Oncol. 2011;41(3):386–93. doi:10.1093/jjco/hyq217.CrossRefPubMedGoogle Scholar