Genetic variants in miR-196a2 and miR-499 are associated with susceptibility to esophageal squamous cell carcinoma in Chinese Han population
Esophageal squamous cell carcinoma (ESCC) is the dominant type of esophageal cancer in the East Asian population. MicroRNAs (miRNAs) have been studied to play important roles in tumorigenesis. Single nucleotide polymorphisms (SNPs) in miRNA lead to the aberrant expression and structural alteration of miRNA and are hypothesized to be involved in tumorigenesis and cancer development. We conducted a population-based case-control study to evaluate the association between SNPs in miRNAs and ESCC risk in 1400 ESCC cases and 2185 matched controls. Four SNPs including miR-196a2 rs11614913, miR-146a rs2910164, miR-499 rs3746444, and miR-423 rs6505162 were selected with comprehensive collection strategy and genotyped using the SNaPshot Multiplex System. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of association. The CC genotype of miR-196a2 rs11614913 was significantly associated with an increased ESCC risk compared with the TT genotype (OR 1.11, 95 % CI 1.01–1.22, P 0.049) and the TT/TC genotypes (OR 1.09, 95 % CI 1.01–1.19, P 0.043). The association was more pronounced in non-drinkers in the recessive model (OR 1.13, 95 % CI 1.01–1.27, P 0.029). A significantly increased risk of ESCC associated with miR-499 rs3746444 polymorphism was evident among patients who never smoking and drinking. This study suggests that miR-196a2 rs11614913 and miR-499 rs3746444 are associated with an increased ESCC risk in a Chinese population.
KeywordsESCC susceptibility miR-196a2 miR-499 rs11614913 rs3746444
Esophageal squamous cell carcinoma
Single nucleotide polymorphism
Receiver operating characteristic
Area under the curve
This work was supported by the grant from the National Natural Science Foundation of China (grant number 81071957), National Natural Science Foundation of China (grant number 81572923), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Key Project in the National Science & Technology Pillar Program (grant number 2011BAI09B00), The Ministry of Health (grant number 201002007), and the funds from “China’s Thousand Talents Program” at Fudan University.
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Conflicts of interest
- 6.Zhang P, Wang J, Lu T, Wang X, Zheng Y, Guo S, et al. miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma in a Chinese population. Tumour Biol. Jun 9 2015.Google Scholar
- 10.Zempleni J, Baier SR, Howard KM, Cui J. Gene regulation by dietary microRNAs. Can J Physiol Pharmacol. 2015;14:1–6.Google Scholar
- 16.Tong N, Xu B, Shi D, Du M, Li X, Sheng X, et al. Hsa-miR-196a2 polymorphism increases the risk of acute lymphoblastic leukemia in Chinese children. Mutat Res. 2013;28:16–21.Google Scholar