Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, Rhode Island 02903, USA.
Clin Cancer Res. 2010 Jul 15;16(14):3713-20. doi: 10.1158/1078-0432.CCR-10-0657. Epub 2010 May 25.
The central role of microRNAs as regulators of translation has been well established, whereas the relationships between genetic variation in microRNAs and disease risk is only beginning to be explored. A polymorphism in the MIR196A2 locus has shown associations with lung, breast, esophageal, and gastric tumors but has not been examined in head and neck cancers, which share similar pathology and etiology to these diseases.
We studied a polymorphism in the mature sequence of MIR196A2 (rs11614913, C/T) in a population-based case-control study (n = 1,039) of head and neck squamous cell carcinoma (HNSCC) to determine if MIR196A2 genotype was associated with disease occurrence and patient survival.
Presence of any variant allele was associated with a significantly reduced risk for HNSCC (odds ratio, 0.8; 95% confidence interval, 0.56-0.99). Homozygous variant allele carriers with pharyngeal tumors had significantly reduced survival compared with wild-type and heterozygous cases (hazard ratio, 7.4; 95% confidence interval, 1.9-28.2). Expression analysis in a subset of tumors (n = 83) revealed no significant difference in relative expression of either miR-196a or miR-196a* by MIR196A2 genotype.
These data demonstrate a role for MIR196A2 genotype in susceptibility and prognosis of HNSCC.
微 RNA 作为翻译调节剂的核心作用已得到充分证实，而微 RNA 遗传变异与疾病风险之间的关系才刚刚开始被探索。MIR196A2 基因座的一个多态性与肺癌、乳腺癌、食管癌和胃癌有关，但尚未在头颈部癌症中进行检查，头颈部癌症与这些疾病具有相似的病理和病因。
我们在一项基于人群的头颈部鳞状细胞癌（HNSCC）病例对照研究（n=1039）中研究了 MIR196A2 成熟序列中的一个多态性（rs11614913，C/T），以确定 MIR196A2 基因型是否与疾病发生和患者生存有关。
任何变异等位基因的存在与 HNSCC 的风险显著降低相关（比值比，0.8；95%置信区间，0.56-0.99）。与野生型和杂合子病例相比，咽部肿瘤的纯合变异等位基因携带者的生存时间明显缩短（风险比，7.4；95%置信区间，1.9-28.2）。在肿瘤的一个亚组（n=83）的表达分析中，MIR196A2 基因型对 miR-196a 或 miR-196a*的相对表达没有显著差异。
这些数据表明 MIR196A2 基因型在 HNSCC 的易感性和预后中起作用。
