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Purpose  Caspase 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.    Methods  We 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.    Results  There 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.    Conclusions  Our 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.

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