A Functional Variant of the miR-15 Family Is Associated with a Decreased Risk of Esophageal Squamous Cell Carcinoma.

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.