A functional variant at miRNA-122 binding site in IL-1a 3' UTR predicts risk of recurrence in patients with oropharyngeal cancer.
A functional variant at miRNA-122 binding site in IL-1a 3' UTR predicts risk of recurrence in patients with oropharyngeal cancer.
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DOI：
10.18632/oncotarget.8908
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Wang C;Sturgis EM;Chen X;Wei Q;Li G
IL-1α是免疫和炎症反应的重要调节因子，与癌症的发展和预后有关。IL-1α 3 ' UTR中的插入(Ins)/缺失（Del）多态性（IL-1α rs3783553）可能破坏miRNA-122的结合位点并可能影响其转录水平。因此，这种多态性可能导致免疫和炎症反应的个体间差异，从而可能导致这类患者对治疗反应和预后的不同易感性。我们在1008例患者中评估了IL-1α rs3783553多态性与口咽部鳞状细胞癌（SCCOP）复发风险的关系。使用Log-rank检验和单变量和多变量Cox模型来评估相关性。与Del/Del纯合基因型患者相比，Ins/Del+Ins/Ins变异基因型患者的无病生存期较差（log-rank P < 0.0001），经多变量校正后SCCOP复发风险增加（HR, 2.4, 95% CI, 1.7-3.3）。此外，在hpv16阳性肿瘤患者中，IL-1α多态性的Ins/Del+Ins/Ins变异基因型患者的无病生存期较差（log-rank P < 0.0001），其复发风险远高于该多态性的Del/Del纯合基因型患者（HR, 16.3, 95% CI, 5.0-52.7）。我们的研究结果表明，IL-1α rs3783553多态性可能调节患者，特别是hpv16阳性肿瘤患者的SCCOP复发风险。然而，需要更大规模的研究来验证这些结果。
IL-1α, an important regulator of immune and inflammation responses, has been implicated in cancer development and prognosis. An insertion (Ins)/deletion (Del) polymorphism (IL-1α rs3783553) in the 3′ UTR of IL-1α may disrupt a binding site for miRNA-122 and may affect its transcription level. Thus, this polymorphism may cause interindividual variation in immune and inflammation responses and thus may lead to different susceptibility to treatment response and prognosis of such patients. We evaluated the association of IL-1α rs3783553 polymorphism with risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP) in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate associations. Compared with patients with Del/Del homozygous genotype, the patients with Ins/Del+Ins/Ins variant genotypes had worse disease-free survival (log-rank P < 0.0001) and increased risk of SCCOP recurrence (HR, 2.4, 95% CI, 1.7-3.3) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with Ins/Del+Ins/Ins variant genotypes of the IL-1α polymorphism had worse disease-free survival (log-rank P < 0.0001) and much higher recurrence risk than those with Del/Del homozygous genotype of this polymorphism (HR, 16.3, 95% CI, 5.0-52.7). Our findings suggest that IL-1α rs3783553 polymorphism may modulate the risk of SCCOP recurrence in patients, particularly for patients with HPV16-positive tumors. However, larger studies are needed to validate these results.
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DOI：
10.1016/j.cbpb.2013.12.002
发表时间：
2014-03-01
影响因子：
2.2
作者：
Mennigen, Jan A.;Plagnes-Juan, Elisabeth;Skiba-Cassy, Sandrine
通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
4.7
作者：
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通讯作者：
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影响因子：
45.3
作者：
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通讯作者：
Gillison, Maura L.