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

Theodoros N. Sergentanis (1, 2) , Konstantinos P. Economopoulos (1, 2)

1 School of Medicine
2 Society of Junior Doctors

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 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 carriers: pooled OR = 0.944, 95% CI: 0.884–1.008). The random effects model in Chinese subjects has not reached statistical significance (for 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.

Mots clés: CASP8 D302H; CASP8 −652 6N del; Caspase-8; Polymorphism; Breast cancer

Theodoros N. Sergentanis, Konstantinos P. Economopoulos. Association of two CASP8 polymorphisms with breast cancer risk: a meta-analysis. Breast Cancer Research and Treatment, 2009, 120 (1), pp.229-234. ⟨10.1007/s10549-009-0471-5⟩. ⟨hal-00535385⟩