CASP8-652 6Ndel 多态性与结直肠癌易感性相关：来自荟萃分析的证据。
CASP8 -652 6N del polymorphism contributes to colorectal cancer susceptibility: evidence from a meta-analysis.
机构信息
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Anal and Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
出版信息
PLoS One. 2014 Feb 3;9(2):e87925. doi: 10.1371/journal.pone.0087925. eCollection 2014.
OBJECTIVE
Caspase-8 (CASP8) plays a central role in the apoptotic pathway and aberrant regulation of this pathway may cause cancers. Previous studies investigating the association between CASP8 -652 6N ins/del polymorphism and colorectal cancer (CRC) risk showed inconclusive results. We performed a meta-analysis of all available studies to investigate this association.
METHODS
All studies published up to October 2013 on the association between CASP8 -652 6N ins/del polymorphism and CRC risk were identified by searching electronic databases PubMed, EMBASE, and Cochrane library. The association between CASP8 -652 6N ins/del polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).
RESULTS
Six studies with 6,325 cases and 6,842 controls were included in the meta-analysis. We observed that the CASP8 -652 6N ins/del polymorphism was significantly correlated with CRC risk when all studies were pooled into the meta-analysis (ins/del vs. ins/ins: OR = 0.890, 95%CI 0.821-0.964, P = 0.004; del/del + ins/del vs. ins/ins: OR = 0.899, 95%CI 0.833-0.970, P = 0.006). In stratified analyses by ethnicity, source of control, and quality score, significant association was observed in Asians (ins/del vs. ins/ins: OR = 0.862, 95%CI 0.761-0.977, P = 0.020; del/del + ins/del vs. ins/ins: OR = 0.845, 95%CI 0.749-0.953, P = 0.006), population-based studies (ins/del vs. ins/ins: OR = 0.890, 95%CI 0.813-0.975, P = 0.012; del/del + ins/del vs. ins/ins: OR = 0.901, 95%CI 0.827-0.982, P = 0.018), and high quality studies. However, in subgroup analysis according to cancer location, no significant association was detected.
CONCLUSIONS
The present meta-analysis suggests that the CASP8 is a candidate gene for CRC susceptibility. The CASP8 -652 6N ins/del polymorphism may play a protective role in CRC development especially among Asians. Further large and well-designed studies are needed to confirm this association.
目的
半胱氨酸天冬氨酸蛋白酶-8（CASP8）在凋亡途径中发挥核心作用，该途径的异常调节可能导致癌症。先前研究探讨了 CASP8 -652 6N ins/del 多态性与结直肠癌（CRC）风险之间的关联，但结果并不一致。我们进行了一项荟萃分析，以研究这种关联。
方法
通过检索电子数据库 PubMed、EMBASE 和 Cochrane 图书馆，查找截至 2013 年 10 月有关 CASP8 -652 6N ins/del 多态性与 CRC 风险关联的所有研究。使用比值比（OR）及其 95%置信区间（CI）评估 CASP8 -652 6N ins/del 多态性与 CRC 风险之间的关联。
结果
共有 6 项研究纳入了 6325 例病例和 6842 例对照进行荟萃分析。我们发现，当所有研究合并进行荟萃分析时，CASP8 -652 6N ins/del 多态性与 CRC 风险显著相关（ins/del 与 ins/ins：OR=0.890，95%CI 0.821-0.964，P=0.004；del/del+ins/del 与 ins/ins：OR=0.899，95%CI 0.833-0.970，P=0.006）。按种族、对照来源和质量评分进行分层分析，在亚洲人群中观察到显著关联（ins/del 与 ins/ins：OR=0.862，95%CI 0.761-0.977，P=0.020；del/del+ins/del 与 ins/ins：OR=0.845，95%CI 0.749-0.953，P=0.006）、基于人群的研究（ins/del 与 ins/ins：OR=0.890，95%CI 0.813-0.975，P=0.012；del/del+ins/del 与 ins/ins：OR=0.901，95%CI 0.827-0.982，P=0.018）和高质量研究中。然而，按癌症部位进行亚组分析时，未检测到显著关联。
结论
本荟萃分析表明，CASP8 是 CRC 易感性的候选基因。CASP8 -652 6N ins/del 多态性可能在 CRC 发生发展中发挥保护作用，尤其是在亚洲人群中。需要进一步进行大规模和精心设计的研究来证实这种关联。
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