CASP8 -652 6N Del Polymorphism Contributes to Colorectal Cancer Susceptibility: Evidence from a Meta-Analysis

Qiliu Peng,Shan Li,Taijie Li,Jian Wang,Xue Qin,Ruolin Li,Weizhong Tang,Xianjun Lao,Yan Deng,Zhiping Chen,Gayle E Woloschak

doi:10.1371/journal.pone.0087925

Qiliu Peng, Shan Li + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0087925

Copy DOI

Abstract

ObjectiveCaspase-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.MethodsAll 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).ResultsSix 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.ConclusionsThe 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.

Highlights

Colorectal cancer (CRC) is the second most commonly diagnosed cancer with over 1.2 million new cases and 608,700 deaths in 2008 [1,2]
Genetic polymorphisms for genes controlling cell cycle or apoptosis have been found to modulate the risk for human malignancies [4,5]
Del polymorphism and CRC risk was assessed by odds ratios (ORs) with 95% confidence intervals (CIs)

Summary

Introduction

Colorectal cancer (CRC) is the second most commonly diagnosed cancer with over 1.2 million new cases and 608,700 deaths in 2008 [1,2]. The highest incidence rate of CRC is found in Australia, Europe, and North America. The incidence rate of CRC is rapidly increasing in a number of countries within Eastern Asia, such as China [2]. The development and progression of CRC involves unregulated epithelial cell proliferation due to a series of accumulated genetic alteration [3]. Evidence has shown that prolonged survival of such genetically unstable colorectal epithelial cells, leading eventually to their ultimate malignant transformation, is associated with progressive inhibition of apoptosis. Genetic polymorphisms for genes controlling cell cycle or apoptosis have been found to modulate the risk for human malignancies [4,5]

Methods

Results

Conclusion