Sun Yan, Yu Wenbin, Sturgis Erich M, Peng Wei, Lei Dapeng, Wei Qingyi, Song Xicheng, Li Guojun
Department of Head and Neck Surgery, Unit 1445, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, China.
BMC Cancer. 2016 Feb 8;16:70. doi: 10.1186/s12885-016-2110-y.
FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM).
In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations.
The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1-3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients.
These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner.
FAS/FASL启动子变异被认为会改变这些基因的转录活性，从而改变细胞死亡的调控。然而，尚无研究调查肿瘤部位是否会影响FAS/FASL基因多态性与第二原发性恶性肿瘤（SPM）风险之间的关联。
在本研究中，对752例口咽癌（OPC）患者和777例非OPC患者的FAS670 A>G、FAS1377 G>A、FASL124 A>G和FASL844C>T基因多态性进行基因分型。采用单变量和多变量Cox比例风险模型评估关联。
单变量和多变量分析显示，与以FASL844 CC基因型为参照组相比，患有原发性OPC且具有FASL844 CT/TT基因型的患者发生SPM的风险显著增加（校正危险比[cHR]，2.5；95%置信区间[CI]，1.1 - 5.8，P = 0.043；调整后危险比[aHR]，2.7；95% CI，1.2 - 6.0，P = 0.032）；而患有原发性非OPC且具有FAS670 AG/GG和FasL844 CT/TT基因型的患者发生SPM的风险显著增加（cHR分别为2.2和1.8；95% CI，1.2 - 5.7和1.1 - 3.2；P分别为0.04和0.041；aHR分别为2.4和1.7；95% CI，1.1 - 5.1和1.0 - 3.0；P分别为0.043和0.049），与各自相应的AA和CC基因型相比。此外，在原发性非OPC患者中，携带更多FAS/FASL变异的患者发生SPM的风险显著增加。分层分析显示，吸烟状态对原发性非OPC患者与OPC患者中FAS/FASL基因多态性与SPM风险之间的关联产生不同的影响。
这些结果表明，FAS/FASL基因多态性可能以肿瘤部位特异性方式显著改变头颈部鳞状细胞癌（SCCHN）患者的SPM风险。
