Department of Epidemiology and Health Statistics, School of Public Health, Beijing Municipal Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, China.
Department of Molecular Physiology and Biophysics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
DNA Cell Biol. 2020 Sep;39(9):1583-1594. doi: 10.1089/dna.2020.5606. Epub 2020 Jul 7.
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 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.
微小 RNA（miRNA）相关的单核苷酸多态性（SNP）已被证明与不同类型的癌症易感性有关，包括食管鳞状细胞癌（ESCC）。鉴定 miRNA 相关 SNP 可能为 ESCC 的早期诊断提供候选生物标志物。我们进行了全基因组微阵列分析，以鉴定差异表达的 miRNA，表明 miR-15 家族可能在 ESCC 生物学中发挥重要作用。然后，我们研究了 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 miR-15 家族相关 SNP 进行了基因分型。使用条件逻辑回归评估这些 SNP 与 ESCC 的关系。广义多因子降维分析用于分析 SNP-SNP 和 SNP-吸烟相互作用。查询表达数量性状基因座（eQTL）数据库进行功能验证。我们发现 miR-15b SNP rs1451761T>G 与 ESCC 风险显著降低相关，并且 rs1451761 和 rs2740545 之间存在显著的 SNP-SNP 相互作用。SNP-吸烟相互作用分析还表明，rs1451761 与 ESCC 风险的关联可能因吸烟状况而改变。此外，eQTL 分析表明 rs1451761 与结构维持染色体 4 和载体蛋白亚基α4 mRNA 表达显著相关。我们的结果表明，miR-15b SNP rs1451761 可能单独影响个体对 ESCC 的易感性，以及 SNP-SNP 和 SNP-吸烟相互作用方式。
