Genetic variants in miR-196a2 and miR-499 are associated with susceptibility to esophageal squamous cell carcinoma in Chinese Han population

Fangyuan Shen, Jiejun Chen, Shicheng Guo, Yinghui Zhou, Yabiao Zheng, Yajun Yang, Junjie Zhang, Xiaofeng Wang, Chenji Wang, Dunmei Zhao, Mengyun Wang, Meiling Zhu, Lixia Fan, Jiaqing Xiang, Yong Xia, Qingyi Wei, Li Jin, Jiucun Wang, Minghua Wang
Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine 2016, 37 (4): 4777-84
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.

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