CASP-8-652 6N ins/del polymorphism and cancer risk: A literature-based systematic HuGE review and meta-analysis

Caspase-8 (encoded by the CASP-8 gene) is crucial in generating cell death signals and eliminating potentially malignant cells. Genetic variation in CASP8 may affect susceptibility to cancer. The CASP-8 -652 6N ins/del (rs3834129) polymorphism has been previously reported to influence the progression to several cancers. However, the overall reported studies have shown inconsistent conclusions. In this human genome epidemiology (HuGE) review and meta-analysis, the aim was to identify the association between CASP-8 -652 6N ins/del polymorphism and cancer risk. According to the inclusion criteria, 19 case-control studies with a total of 23,172 cancer cases and 26,532 healthy controls were retrieved. Meta-analysis results showed that the del allele, del allele carrier and ins/del genotype of -652 6N ins/del in the CASP-8 gene were negatively associated with cancer risk (OR=0.91, 95% CI=0.84-0.98, P=0.01; OR=0.88, 95% CI=0.80-0.96, P=0.005; OR=0.91, 95% CI=0.85-0.98, P<0.001; respectively, while no significant correlation was observed between the del/del genotype of -652 6N ins/del and cancer risk (OR=0.89, 95% CI=0.79-1.01, P=0.08). In the subgroup analysis by ethnicity, the meta-analysis indicated that Caucasian populations harboring the del allele, del allele carriers and ins/del genotype had a lower cancer risk (OR=0.96, 95% CI=0.93-1.00, P=0.05; OR=0.86, 95% CI=0.75-1.00, P=0.05; OR=0.91, 95% CI=0.84-0.98, P=0.01; respectively). In addition, a negative association was found between the del allele of -652 6N ins/del in the CASP-8 gene and cancer risk in the Asian population (OR=0.89, 95% CI=0.83-0.97, P=0.005). In conclusion, this meta-analysis suggests that the del allele, del allele carrier and ins/del genotype of the -652 6N ins/del polymorphism in the CASP-8 gene may be protective factors for cancer risk.