Lu Zhongming, Zhang Hua, Tao Ye, Li Xiangping, Li Guojun
Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oncotarget. 2017 Sep 30;8(49):86710-86717. doi: 10.18632/oncotarget.21414. eCollection 2017 Oct 17.
The increasing incidence of squamous cell carcinoma of the oropharynx (SCCOP) is majorly attributed to the human papillomavirus (HPV) infection. Both HPV and MDM4 play a critical role in inhibition of p53 activity, thus affecting HPV tumor status of SCCOP. Three polymorphisms in were genotyped from blood genomic DNA samples and HPV16 status in tumor specimens was examined. Odds ratio (OR) and 95% confidence intervals (CIs) in univariate and multivariable logistic regression models were calculated for the associations between these polymorphisms and HPV16 status. Three variant genotypes were significantly associated with HPV16 tumor status among SCCOP patients compared with the common homozygous genotypes (OR, 0.6; 95% CI, 0.4-1.0 for rs10900598; OR, 1.6, 95% CI; 1.1-2.4 for rs1380576; and OR, 1.8, 95% CI, 1.1-2.9 for rs11801299; respectively). When we combined all risk genotypes of the 3 polymorphisms, the patients carrying 1-3 risk genotypes were approximately 2.5 time as likely to have an HPV16-positive tumor than those with no risk genotypes (OR, 2.5, 95% CI, 1.6-3.9). Additionally, modifying effect of risk genotypes was more pronounced among non-Hispanic white, never-smokers, and never-drinkers. Potential functional polymorphisms in may serve as biomarkers for predicting tumor HPV16 status among SCCOP patients, particularly in non-Hispanic white, never-smokers and never-drinkers. However, validation of these results in larger studies is needed.
口咽鳞状细胞癌(SCCOP)发病率的上升主要归因于人乳头瘤病毒(HPV)感染。HPV和MDM4在抑制p53活性方面均起关键作用,从而影响SCCOP的HPV肿瘤状态。从血液基因组DNA样本中对三个基因的多态性进行基因分型,并检测肿瘤标本中的HPV16状态。计算单变量和多变量逻辑回归模型中这些多态性与HPV16状态之间关联的优势比(OR)和95%置信区间(CI)。与常见纯合基因型相比,SCCOP患者中三种基因的变异基因型与HPV16肿瘤状态显著相关(rs10900598的OR为0.6;95%CI为0.4 - 1.0;rs1380576的OR为1.6,95%CI为1.1 - 2.4;rs11801299的OR为1.8,95%CI为1.1 - 2.9)。当我们将这三个多态性的所有风险基因型合并时,携带1 - 3个风险基因型的患者发生HPV16阳性肿瘤的可能性约为无风险基因型患者的2.5倍(OR为2.5,95%CI为1.6 - 3.9)。此外,风险基因型的修饰作用在非西班牙裔白人、从不吸烟者和从不饮酒者中更为明显。这些基因中的潜在功能性多态性可能作为预测SCCOP患者肿瘤HPV16状态的生物标志物,特别是在非西班牙裔白人、从不吸烟者和从不饮酒者中。然而,需要在更大规模的研究中验证这些结果。