The CASP8 -652 6N insertion/deletion (I/D) polymorphism reduces expression of caspase 8. We conducted a meta-analysis to clarify the relationship between this polymorphism and cancer risk. Eligible articles were retrieved from PubMed, EMBASE, CNKI, and WANFANG databases through February 2017. A total of 33 articles with 49 studies, including 33,494 cases and 36,397 controls, were analyzed. We found that the CASP8 -652 6N ins/del polymorphism was associated with decreased overall cancer risk in five genetic models [DD vs. II: odds ratio (OR)=0.76, 95% confidence interval (CI)=0.69–0.84, ID vs. II: OR=0.87, 95% CI=0.83–0.92, DD vs. ID/II: OR=0.82, 95% CI=0.75–0.89, ID/DD vs. II: OR=0.85, 95% CI=0.80–0.90, and D vs. I: OR=0.87, 95% CI=0.83–0.91]. Stratified analyses showed that the polymorphism was associated with decreased risk of colorectal, breast, esophageal, renal cell, lung, cervical, bladder, gastric, and other cancers. Overall cancer risk was reduced in Asian and Caucasian patients, both hospital- and population-based studies, and both high and low quality studies. Our results highlight the role of the CASP8 -652 6N ins/del polymorphism in decreasing cancer risk. Further studies with large-cohort populations, especially for specific cancer types and ethnic groups, are needed to confirm our findings.
