Several potentially functional polymorphisms of CASP8 encoding an apoptotic
enzyme,
caspase 8, have been implicated in
cancer risk, but individually published studies showed inconclusive results. We performed a meta-analysis of 23 publications with a total of 55 174
cancer cases and 59 336 controls from 55 individual studies. We summarized the data on the associations between three studied CASP8 polymorphisms (G>C D302H, -652 6N del and Ex14-271A>T) and
cancer risk and performed subgroup analysis by ethnicity,
cancer type, study design and etiology. We found that D302H CC and CG variant genotypes were associated with significantly reduced overall risk of
cancers using conservative random genetic models [homozygote comparison: odds ratios (OR) = 0.79; 95% confidence interval (CI): 0.69-0.92; dominant comparison: OR = 0.93, 95% CI: 0.89-0.98; recessive comparison: OR = 0.81, 95% CI: 0.71-0.93). In further stratified analyses, the reduced
cancer risk remained for subgroups of Caucasians, breast or
estrogen-related
cancers, and hospital- or population-based studies, except for an elevated risk for
brain tumors. Similarly, the -652 6N del polymorphism was also associated with significantly reduced overall risk of
cancers (homozygote comparison: OR = 0.84, 95% CI: 0.75-0.94; dominant comparison: OR = 0.88, 95% CI: 0.81-0.96; recessive comparison: OR = 0.90, 95% CI: 0.82-0.99) and all subgroups analyzed. However, the Ex14-271A>T polymorphism did not appear to have an effect on
cancer risk. These results suggest that CASP8 D302H and -652 6N del polymorphisms are potential
biomarkers for
cancer risk.