Association of caspase 8 polymorphisms -652 6N InsDel and Asp302His with progression-free survival and tumor infiltrating lymphocytes in early breast cancer.
Our results support that the presence of the CASP8D302H polymorphism diminishes the high risk of BC conferred by BRCA1 and BRCA2 mutations, making possible that some of the carriers could escape from suffering BC along their life span.
Further subgroup analysis indicated that CASP8 -652 6N del polymorphism was associated with breast cancer, lung and gastrointestinal cancer susceptibility.
To define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk.
To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC).
The reproducible, dose-dependent association of CASP8 D302H with breast cancer indicates the potential importance of inherited variation in the apoptosis pathway in breast cancer susceptibility.
For Caucasians, CASP8-652 6N del was associated with reduced breast cancer risk at a borderline level (homozygous: OR=0.94, 95% CI 0.86-1.02, heterozygous: OR=0.96, 95% CI 0.90-1.03, recessive: OR=0.96, 95% CI 0.90-1.03, dominant: OR=0.94, 95% CI 0.88-1.01).
Impaired kinetics of Bax-GFP and Smac/DIABLO-GFP in caspase-8- and bid-silenced and Bcl-2 overexpressed breast cancer MCF-7 cells exposed to camptothecin.
We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.
Thus, the suicidal caspase-8/ERα-LBD protein, which reverses the mitogenic effects of estrogens, has potential to provide novel approaches to treating estrogen-dependent and -independent breast cancers.
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.
The CpG sites in the promoter region of CASP8 and maspin were methylated in all four breast cancer cell lines but not in two non-tumorigenic breast cell lines.
We observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p = 0.0131).
Firstly, the induction of apoptosis in human breast cancer MCF-7 and BT549 cells showed that balsamin-induced apoptosis involved increases in caspase-3 and caspase-8 activity, upregulation of Bax, Bid, and Bad, and downregulation of BCL-2 and BCL-XL.
High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively).
Fas/FasL-dependent and -independent activation of caspase-8 in doxorubicin-treated human breast cancer MCF-7 cells: ADAM10 down-regulation activates Fas/FasL signaling pathway.