Genetic Polymorphisms of the CASP8 Gene Promoter May Not Be Associated with Colorectal Cancer in Han Chinese from Southwest China

Abstract

PurposeCaspase 8 (CASP8) plays a critical role in the apoptotic pathway and aberrant regulation of this pathway causes many diseases including cancers. Genetic variants rs3834129 (CTTACT/−) and rs3769821 (T/C) in the promoter region of the CASP8 gene were documented to be associated with multiple solid cancers and non-Hodgkin’s lymphoma (NHL), respectively, despite of some controversies. We aimed to discern potential association of these two variants and rs113686495 (CTGTCATT/−), as well as CASP8 mRNA and protein expression levels with colorectal cancer (CRC) in Han Chinese.MethodsWe genotyped CASP8 genetic variants in 305 CRC patients and 342 healthy individuals from Kunming, Southwest China. Expression levels of CASP8 mRNA and protein were quantified in paired cancerous and paracancerous normal tissues by using real-time quantitative PCR and western blot, respectively. We compared the frequencies of alleles, genotypes, and haplotypes between the cases and controls. Correlation of CASP8 mRNA and protein expression levels in paired cancerous and paracancerous normal tissues from patients with different genotypes and clinical expression were also evaluated.ResultsThere was no association of the CASP8 genetic variants with CRC in our case-control study. The CASP8 gene mRNA expression levels in cancerous and paracancerous normal tissues were similar and there was no significant difference between subjects with different genotypes and clinical features. However, we found that CASP8 protein level was significantly lower in cancerous tissues than in paired paracancerous normal tissues.ConclusionsOur results suggest that the three CASP8 genetic variants may not be associated with CRC risk in Han Chinese from southwest China. Aberrant CASP8 protein expression may play a role in the pathogenesis of CRC.

CASP8 rs3834129 (-652 6N insertion/deletion) Polymorphism and Colorectal Cancer Susceptibility: An Updated Meta-Analysis

“…This study recruited 6,733 CRC cases and 7,576 controls by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (Colorectal cancer GENeTics). Such null associations were also presented in a study conducted by Xiao MS et al in Chinese population using 305 CRC patients and 342 healthy individuals 20 .…”

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

“…Manual search of references cited in the published studies did not reveal any additional articles. As a result, a total of six relevant studies containing 6,325 cases and 6,842 controls were included in the meta-analysis [8] , [19] , [20] , [21] , [22] , [23] ( Figure S1 ). Table 2 lists the main characteristics of these studies.…”

“…Among these publications, two were conducted in Caucasian descent [20] , [21] , and four were conducted in Asian descent [8] , [19] , [22] , [23] . Three were population–based studies [8] , [21] , [22] and three were hospital–based studies [19] , [20] , [23] . Two of these studies [19] , [22] presented CASP8 −652 6N ins/del polymorphism genotype distributions according to cancer location (colon cancer and rectal cancer).…”

“…Two of these studies [19] , [22] presented CASP8 −652 6N ins/del polymorphism genotype distributions according to cancer location (colon cancer and rectal cancer). The cases were histologically or pathologically confirmed as CRC in four studies [19] , [20] , [22] , [23] . Controls were mainly healthy or hospital-based populations and matched with age and gender.…”

Impact of Host Molecular Genetic Variations and HIV/HPV Co-infection on Cervical Cancer Progression: A Systematic review

“…The activation of Caspase 8 (CASP8), represents an important initiating event in the death receptor-induced apoptosis gene. However, the deleted allele of the CASP8 polymorphism has been associated with decreased risk for cervical cancer in a Chinese population (136). Studies in African populations have not found any association between CASP8 polymorphisms and cervical cancer susceptibility (65).…”