Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Environ Mol Mutagen. 2014 Jun;55(5):421-7. doi: 10.1002/em.21856. Epub 2014 Feb 17.
The FAS, FAS ligand (FASL), and CASP8 are key regulators for apoptosis and their deregulations play an important role in carcinogenesis. However, the effects of promoter polymorphisms of the FAS, and FASL, and CASP8 genes on the survival of gastric cancer are unknown. In this study, we investigated the association of four polymorphisms (FAS -1377G>A, -670A>G, FASL -844C>T, and CASP8 -652 6N ins>del) with the clinical outcome of 940 gastric cancer patients in a Chinese population. The correlation between genotype and survival outcomes was assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. Our results revealed that individuals with CASP8 -652 6N ins/del+del/del genotypes had a decreased risk of death compared with those with ins/ins genotype (log-rank P=0.005; hazard ratio=0.75, 95% confidence interval=0.62-0.92). The protective effect of the del allele was further confirmed in subgroups of patients with tumor size ≤ 5 cm (0.66, 0.50-0.86) and T2 depth invasion (0.59, 0.37-0.94), but no significant association was observed in the subgroups of lymph node metastasis (0.67, 0.47-0.97), and distance metastasis (0.73, 0.60-0.90). Our findings suggest that, if validated in different independent populations, the CASP8 -652 6N ins>del polymorphism may serve as a promising genetic marker for gastric cancer prognosis.
FAS、FAS 配体（FASL）和 CASP8 是细胞凋亡的关键调节因子，其失调在肿瘤发生中起着重要作用。然而，FAS、FASL 和 CASP8 基因启动子多态性对胃癌患者生存的影响尚不清楚。在这项研究中，我们研究了四个多态性（FAS-1377G>A、-670A>G、FASL-844C>T 和 CASP8-6526Nins>del）与中国人群 940 例胃癌患者临床结局的关系。通过 Kaplan-Meier 方法、Cox 比例风险模型和对数秩检验评估基因型与生存结果之间的相关性。我们的结果表明，与 ins/ins 基因型相比，CASP8-6526Nins/del+del/del 基因型的个体死亡风险降低（log-rank P=0.005；风险比=0.75，95%置信区间=0.62-0.92）。在肿瘤大小≤5cm（0.66，0.50-0.86）和 T2 深度浸润（0.59，0.37-0.94）的患者亚组中，del 等位基因的保护作用进一步得到证实，但在淋巴结转移（0.67，0.47-0.97）和远处转移（0.73，0.60-0.90）的患者亚组中未观察到显著相关性。我们的研究结果表明，如果在不同的独立人群中得到验证，那么 CASP8-6526Nins>del 多态性可能成为预测胃癌预后的有前途的遗传标志物。
