MicroRNAs (miRNAs)-related single-nucleotide polymorphisms (SNPs) have been shown to be implicated in the susceptibility to different types of cancer, including esophageal squamous cell carcinoma (ESCC). Identification of miRNA-related SNPs may provide candidate biomarkers for early diagnosis of ESCC. We performed a genome-wide microarray assay to identify differentially expressed miRNAs, which indicated that the miR-15 family may play an important role in ESCC biology. We then investigated the association of miR-15 family-related SNPs with ESCC. Five miR-15 family-related SNPs were genotyped in 300 patients and 418 controls. Unconditional logistic regression was used to evaluate the relationships of these SNPs with ESCC. Generalized multifactor dimensionality reduction was employed to analyze the SNP–SNP and SNP–smoking interactions. The expression quantitative trait loci (eQTL) databases were queried for in silico functional validation. We found that miR-15b SNP rs1451761T>G was associated with a significantly decreased risk of ESCC and there was a significant SNP–SNP interaction between rs1451761 and rs2740545. SNP–smoking interaction analysis also indicated that the association between rs1451761 and ESCC risk could be changed by smoking status. Additionally, the eQTL analysis revealed that rs1451761 was significantly correlated with structural maintenance of chromosomes 4 and karyopherin subunit alpha 4 mRNA expression. Our results suggest that miR-15b SNP rs1451761 may affect an individual's susceptibility to ESCC, alone and in SNP–SNP and SNP–smoking interaction manners.

中文翻译：

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miR-15家族的功能变异与食道鳞状细胞癌的风险降低相关。

已显示与MicroRNA（miRNA）相关的单核苷酸多态性（SNP）与包括食管鳞状细胞癌（ESCC）在内的不同类型癌症的易感性有关。与miRNA相关的SNP的鉴定可为ESCC的早期诊断提供候选生物标记。我们进行了全基因组微阵列分析，以鉴定差异表达的miRNA，这表明miR-15家族可能在ESCC生物学中发挥重要作用。然后，我们调查了miR-15家族相关SNP与ESCC的关联。在300名患者和418名对照中对5个与miR-15家庭相关的SNP进行了基因分型。使用无条件逻辑回归来评估这些SNP与ESCC的关系。广义多因素降维被用于分析SNP–SNP和SNP–吸烟的相互作用。在计算机功能验证中。我们发现miR-15b SNP rs1451761T> G与ESCC风险显着降低有关，并且rs1451761和rs2740545之间存在显着的SNP-SNP相互作用。SNP-吸烟相互作用分析还表明，rs1451761与ESCC风险之间的关联可能会因吸烟状况而改变。此外，eQTL分析显示rs1451761与4号染色体的结构维持和核蛋白亚基α4mRNA表达显着相关。我们的结果表明，miR-15b SNP rs1451761可能会单独和以SNP–SNP和SNP–吸烟相互作用方式影响个体对ESCC的易感性。