Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosis.

ABSTRACT

PURPOSE: Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association between CASP8 and CASP9 gene polymorphisms and colorectal cancer (CRC) susceptibility. METHODS: A case-control study at 402 CRC patients and 480 healthy controls was undertaken in order to investigate the association between the genotype and allelic frequencies of CASP8 -652 6N ins/del and CASP9 -1263 A>G polymorphisms and the CRC susceptibility. The polymerase chain reaction (PCR) restriction fragment length polymorphism method was used and the incidence of polymorphisms on messenger RNA (mRNA) expression levels was detected by quantitative reverse-transcriptase PCR in CRC tissues. RESULTS: No statistical significant association was observed between CASP8 -652 6N ins/del polymorphism frequencies and CRC susceptibility. CASP9 -1263 G allele was observed to be significant associated with reduced risk of CRC. Homozygotes for the -1263 GG CASP9 genotype, and hetrozygotes for the -1263 AG genotype expressed 6.64- and 3.69-fold higher mRNA levels of Caspase-9, respectively compared to the -1263 AA genotype cases. No significant association was observed between CASP9 -1263 A>G polymorphism and tumor characteristics. The CASP9 -1263 GG genotype was associated with increased overall survival in CRC patients. CONCLUSION: The CASP9 -1263 A>G polymorphism was observed to play a protective role in CRC predisposition, while the CASP9 -1263 GG genotype may confer a better prognosis at CRC patients.