Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
PLoS One. 2012;7(6):e39777. doi: 10.1371/journal.pone.0039777. Epub 2012 Jun 28.
MicroRNAs (miRNAs) have been regarded as a critical factor in targeting oncogenes or tumor suppressor genes in tumorigenesis. The genetic predisposition of miRNAs-signaling pathways related to the development of oral squamous cell carcinoma (OSCC) remains unresolved. This study examined the associations of polymorphisms with four miRNAs with the susceptibility and clinicopathological characteristics of OSCC.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 895 male subjects, including 425 controls and 470 male oral cancer patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a, miRNA196, miRNA499 and miRNA149 genetic polymorphisms between the control group and the case group. This study determined that a significant association of miRNA499 with CC genotype, as compared to the subjects with TT genotype, had a higher risk (AOR = 4.52, 95% CI = 1.24-16.48) of OSCC. Moreover, an impact of those four miRNAs gene polymorphism on the susceptibility of betel nut and tobacco consumption leading to oral cancer was also revealed. We found a protective effect between clinical stage development (AOR = 0.58, 95% CI = 0.36-0.94) and the tumor size growth (AOR = 0.47, 95% CI = 0.28-0.79) in younger patients (age<60).
Our results suggest that genetic polymorphism of miRNA499 is associated with oral carcinogenesis, and the interaction of the miRNAs genetic polymorphism and environmental carcinogens is also related to an increased risk of oral cancer in Taiwanese.
MicroRNAs（miRNAs）被认为是肿瘤发生中靶向癌基因或肿瘤抑制基因的关键因素。miRNAs 信号通路的遗传易感性与口腔鳞状细胞癌（OSCC）的发展之间的关系仍未解决。本研究探讨了 miRNA 相关多态性与 OSCC 易感性和临床病理特征的相关性。
方法/主要发现：共选择了 895 名男性受试者，包括 425 名对照和 470 名男性口腔癌患者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和实时 PCR 分析对照组和病例组之间 miRNA146a、miRNA196、miRNA499 和 miRNA149 遗传多态性。本研究确定 miRNA499 与 CC 基因型的显著相关性，与 TT 基因型相比，OSCC 的风险更高（AOR=4.52，95%CI=1.24-16.48）。此外，还揭示了这四种 miRNA 基因多态性对食用槟榔和烟草导致口腔癌易感性的影响。我们发现，在年轻患者（年龄<60 岁）中，临床分期发展（AOR=0.58，95%CI=0.36-0.94）和肿瘤大小增长（AOR=0.47，95%CI=0.28-0.79）之间存在保护作用。
我们的结果表明，miRNA499 的遗传多态性与口腔癌发生有关，miRNA 遗传多态性与环境致癌物的相互作用也与台湾人口腔癌风险增加有关。
