Association of two CASP8 polymorphisms with breast cancer risk: a meta-analysis

Caspase-8 (CASP8) is an initiator caspase implicated in the process of apoptosis in breast cancer cells. Attention has been drawn upon two polymorphisms: CASP8 D302H (rs1045485) and, more recently, CASP8 -652 6N del (rs3834129). The CASP8 -652 6N del polymorphism remains an open field, as studies are controversial. This meta-analysis aims to examine: (i) the association between CASP8 -652 6N del and breast cancer risk, separately in Chinese and Caucasian populations, and (ii) the association between CASP8 D302H and breast cancer risk. Eligible articles were identified by a search of MEDLINE, Cochrane, and EMBASE bibliographical databases for the period from June 1996 to July 2009. Regarding -652 6N del, five case-control studies were eligible (12,439 breast cancer cases, 13,253 controls) and four case-control studies were eligible for D302H (18,791 breast cancer cases, 20,318 controls). In case significant heterogeneity was detected, the random effects model was chosen; nevertheless, the fixed effects estimates are also secondarily reported as an alternative approach. Where appropriate, power calculations were performed. CASP8 -652 6N del was associated with reduced breast cancer risk at a borderline level (for del carriers: pooled OR = 0.884, 95% CI: 0.761-1.028); the power calculation pointed to lack of power in the individual studies. In the Caucasian populations, the same results seem valid (for del carriers: pooled OR = 0.944, 95% CI: 0.884-1.008). The random effects model in Chinese subjects has not reached statistical significance (for del carriers: pooled OR = 0.811, 95% CI: 0.492-1.338). CASP8 D302H was associated with reduced breast cancer risk (for H carriers: pooled OR = 0.874, 95% CI: 0.834-0.917). In conclusion, both CASP8 -652 6N del and D302H polymorphisms are associated with reduced cancer risk. Further studies are needed to gain the optimal power on -652 6N del, especially in Chinese subjects, as well as to gain insight into D302H in Chinese populations.