Zhang Fenghua, Sturgis Erich M, Sun Yan, Zhang Yang, Wei Qingyi, Zhang Caiyun, Zheng Hongliang, Li Guojun
Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX.
Department of General Surgery, Hebei General Hospital, Shijiazhuang, Hebei, China.
Int J Cancer. 2015 Nov 15;137(10):2454-61. doi: 10.1002/ijc.29604. Epub 2015 Jul 27.
Single nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.
FAS和FASLG启动子区域的单核苷酸多态性（SNP）可能会改变它们的转录活性。因此，我们确定了四种FAS和FASLG启动子变体（FAS1377G>A，rs2234767；670A>G，rs1800682；FASLG844T>C，rs763110和124A>G，rs5030772）与口咽鳞状细胞癌（SCCOP）复发风险之间的关联。我们在1008名患者的队列中评估了FAS和FASLG基因变体与复发风险之间的关联。采用对数秩检验和多变量Cox模型来评估这些关联。与FAS670和FASLG844多态性常见纯合基因型的患者相比，变体基因型的患者无病生存率较低（对数秩检验p分别<0.0001和<0.0001），并且在多变量调整后SCCOP复发风险大约高3倍（HR，3.2；95%CI，2.2 - 4.6；以及HR，3.1；95%CI，2.2 - 4.4）。此外，在HPV16阳性肿瘤患者中，这两种多态性变体基因型的患者无病生存率较低（对数秩检验，p分别<0.0001和<0.0001），并且复发风险高于常见纯合基因型的患者（HR，12.9；95%CI，3.8 - 43.6；以及HR，8.1；95%CI，3.6 - 18.6），而FAS1377和FASLG124多态性未发现显著关联。我们的研究结果表明，FAS670和FASLG844多态性调节SCCOP的复发风险，特别是在HPV16阳性肿瘤患者中。需要更大规模的研究来验证这些结果。
