Association between main Caspase Gene Polymorphisms and the Susceptibility and Prognosis of Colorectal Cancer

Abstract

Caspase (CASP) 3, 8, 9 are important caspases in the apoptosis pathway and play important roles in development and progression of cancer. A case-control study with 451 colorectal cancer (CRC) patients and 631 cancer-free controls were carried out, and CRC patients followed up, to investigate the associations between three main polymorphisms and colorectal cancer risk and prognosis, and their potential interactions with environmental factors on CRC risk among Chinese people. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction-single strand conformation polymorphism sequencing. Odds ratio (OR), hazard ratio (HR) and their 95% confidence intervals (CIs) were estimated with unconditional logistic-regression and Cox proportion hazard model. Individuals harboring the CASP8 -652 6N ins/del plus del/del genotype had a slightly lower risk for CRC compared those with ins/ins genotype (adjusted OR=0.77, 95% CI 0.59-0.99, P=0.04). Significant associations between CASP3 -928 GG genotype and CASP9 -1263 GG genotype and reduced risk of rectal cancer were observed (adjusted OR=0.56, 95% CI 0.34-0.92, P=0.02; adjusted OR=0.59, 95% CI 0.36-0.95, P=0.03, respectively). There was a marginal significant association between CASP8 -652 6N ins/del polymorphism and CRC prognosis (ins/del versus ins/ins, adjusted HR=0.69, 95% CI 0.48-0.99, P=0.04). These findings suggested these polymorphisms and their combinations with dietary factors may be associated with the development of CRC. CASP8 -652 6N ins/del polymorphism may be an independent survival predictor for CRC.