MicroRNA-101 polymorphisms and risk of head and neck squamous cell carcinoma in a Chinese population

MicroRNAs (miRNAs) play important roles in regulation of gene expressions and likely have involvement in cancer susceptibility and disease progression. MicroRNA-101 (miR-101) has been well established as a tumor suppressor, and aberrant expression of miR-101 levels has been previously reported in different malignancies including head and neck squamous cell carcinoma (HNSCC). However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in the susceptibility to HNSCC remains unclear. In this study, we genotyped 11 selected SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case-control study including 576 HNSCC cases and 1552 cancer-free controls. For the main effect analysis, none of the 11 selected SNPs was associated with HNSCC risk. However, in the stratification analysis by tumor sites, rs578481 and rs705509 in pri-miR-101-1 were significantly associated with risk of oral squamous cell carcinoma (OSCC) (rs578481: adjusted odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.01-1.39, P = 0.036; rs705509: adjusted OR = 0.85, 95 % CI 0.73-0.98, P = 0.030). Furthermore, combined analysis of the two SNPs revealed that subjects carrying the risk alleles of rs578481 and rs705509 had increased risk of OSCC in a dose-response manner (P trend = 0.022). Compared with subjects carrying "0-2" risk alleles, subjects carrying "3-4" risk alleles presented a 1.38-fold increased risk of OSCC. In conclusion, our findings suggested that the SNPs rs578481 and rs705509 locating in pri-miR-101-1 may play a role in genetic susceptibility to OSCC, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.