Hou Y-Y, Lee J-H, Chen H-C, Yang C-M, Huang S-J, Liou H-H, Chi C-C, Tsai K-W, Ger L-P
Department of Otorhinolaryngology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Nursing, Yuh-Ing Junior College of Health Care and Management, Kaohsiung, Taiwan.
Oral Dis. 2015 Mar;21(2):195-206. doi: 10.1111/odi.12241. Epub 2014 Apr 24.
To investigate the association of miR-499a genetic polymorphism with the risk of oral leukoplakia, oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC), and clinicopathological outcomes of OSCC.
The genotyping of miR-499a T>C (rs3746444) using TagMan assay was conducted in two case-control studies of 1549 subjects. miR-499a-5p and miR-499a-3p were assayed using stem-loop RT-PCR for 63 paired OSCC and adjacent normal tissues.
T/C+C/C genotypes [adjusted odds ratio (AOR) 1.84, P = 0.032] and C allelic type (AOR 1.91, P = 0.007) at miR-499a T>C were associated with an increased risk of BQ-related OSF as compared to those with T/T genotype or T allelic type, respectively. Conversely, T/C+C/C genotypes and C allelic type decreased the risk of OSCC, especially for non-BQ-related OSCC (for genotype: AOR 0.49, P = 0.010; for allelic type: AOR 0.50, P = 0.007). Additionally, downregulation of miR-499a-5p was found in OSCC tissues (P = 0.001) and correlated with the TT genotype (P = 0.001).
The T/C+C/C genotypes of MiR-499a may contribute to an increased risk of BQ-related OSF, but a decreased risk of OSCC. miR-499a T>C influences the expression levels of miR-499a-5p during the tumorigenesis of OSCC.
探讨miR-499a基因多态性与口腔白斑、口腔黏膜下纤维化（OSF）、口腔鳞状细胞癌（OSCC）风险以及OSCC临床病理结果之间的关联。
在两项涉及1549名受试者的病例对照研究中，采用TaqMan分析对miR-499a T>C（rs3746444）进行基因分型。使用茎环逆转录聚合酶链反应（stem-loop RT-PCR）对63对OSCC及其癌旁正常组织检测miR-499a-5p和miR-499a-3p。
与T/T基因型或T等位基因类型相比，miR-499a T>C位点的T/C+C/C基因型[校正比值比（AOR）1.84，P = 0.032]和C等位基因类型（AOR 1.91，P = 0.007）分别与槟榔碱相关的OSF风险增加有关。相反，T/C+C/C基因型和C等位基因类型降低了OSCC的风险，尤其是对于非槟榔碱相关的OSCC（基因型：AOR 0.49，P = 0.010；等位基因类型：AOR 0.50，P = 0.007）。此外，在OSCC组织中发现miR-499a-5p表达下调（P = 0.001），且与TT基因型相关（P = 0.001）。
MiR-499a的T/C+C/C基因型可能导致槟榔碱相关的OSF风险增加，但OSCC风险降低。miR-499a T>C在OSCC肿瘤发生过程中影响miR-499a-5p的表达水平。
