CASP8 -652 6N del polymorphism contributes to colorectal cancer susceptibility: evidence from a meta-analysis.
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.
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Qiliu
Q
Peng
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Xianjun
X
Lao
Department of Anal and Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Weizhong
W
Tang
Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi, China.
Zhiping
Z
Chen
Department of Medicine Research, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Ruolin
R
Li
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Jian
J
Wang
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Yan
Y
Deng
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Taijie
T
Li
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Xue
X
Qin
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Shan
S
Li
D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*
C505530:CASP8 protein, human; D053181:Caspase 8