Zhu Lijun, Sturgis Erich M, Zhang Hua, Lu Zhongming, Tao Ye, Wei Qingyi, Li Guojun
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Oral and Maxillofacial Surgery, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China.
Int J Cancer. 2017 Oct 1;141(7):1355-1364. doi: 10.1002/ijc.30849. Epub 2017 Jul 7.
The incidence of squamous cell carcinoma of the oropharynx (SCCOP) continues to rise because of increasing rates of human papillomavirus (HPV) infection. Inherited polymorphisms in DNA repair pathways may influence the risk of SCCOP development and the prognosis of SCCOP. We sought to determine whether polymorphisms in microRNA (miRNA)-binding sites within 3'-untranslated regions (3'UTRs) of genes in DNA repair pathways modulate the risk of SCCOP recurrence. We evaluated the associations between nine such polymorphisms and SCCOP recurrence in 1,008 patients with incident SCCOP using the log-rank test and multivariable Cox models. In an analysis of all the patients, patients with variant genotypes of BRCA1 rs12516 and RAD51 rs7180135 had better disease-free survival (log-rank, p = 0.0002 and p = 0.0003, respectively) and lower risk of SCCOP recurrence (hazard ratio [HR], 0.5, 95% confidence interval [CI], 0.2-0.8, and HR, 0.5, 95% CI, 0.3-0.9, respectively) than patients with common homozygous genotypes of the two polymorphisms after multivariable adjustment. Moreover, in tumor HPV16-positive patients, patients with variant genotypes of the same two polymorphisms also had better disease-free survival (log-rank, p = 0.004 and p = 0.003, respectively) and lower recurrence risk (HR, 0.2, 95% CI, 0.1-0.6, and HR, 0.2, 95% CI, 0.0-0.7, respectively) than patients with common homozygous genotypes of the two polymorphisms. No such significant associations were found for other polymorphisms. These findings support significant roles of BRCA1 rs12516 and RAD51 rs7180135 in modifying the risk of recurrence of SCCOP, particularly HPV16-positive SCCOP. However, these results must be validated in larger studies.
由于人乳头瘤病毒（HPV）感染率不断上升，口咽鳞状细胞癌（SCCOP）的发病率持续升高。DNA修复途径中的遗传多态性可能会影响SCCOP的发生风险和预后。我们试图确定DNA修复途径中基因的3'非翻译区（3'UTR）内微小RNA（miRNA）结合位点的多态性是否会调节SCCOP复发的风险。我们使用对数秩检验和多变量Cox模型评估了1008例新发SCCOP患者中9种此类多态性与SCCOP复发之间的关联。在对所有患者的分析中，与两种多态性的常见纯合基因型患者相比，携带BRCA1 rs12516和RAD51 rs7180135变异基因型的患者无病生存期更好（对数秩检验，p分别为0.0002和0.0003），SCCOP复发风险更低（风险比[HR]分别为0.5，95%置信区间[CI]为0.2 - 0.8；HR为0.5，95% CI为0.3 - 0.9），多变量调整后也是如此。此外，在肿瘤HPV16阳性患者中，携带相同两种多态性变异基因型的患者与两种多态性的常见纯合基因型患者相比，无病生存期也更好（对数秩检验，p分别为0.004和0.003），复发风险更低（HR分别为0.2，95% CI为0.1 - 0.6；HR为0.2，95% CI为0.0 - 0.7）。其他多态性未发现此类显著关联。这些发现支持BRCA1 rs12516和RAD51 rs7180135在改变SCCOP复发风险中发挥重要作用，尤其是HPV16阳性的SCCOP。然而，这些结果必须在更大规模的研究中得到验证。
