Caspase-8 (CASP-8) is an initiator CASP in the cell death receptor-mediated apoptotic pathway, and plays an important role in the development of cancer. Polymorphisms and their haplotypes in the CASP-8 gene can result in alterations in CASP-8 expression and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we examined the association of -678_-673delAGTAAG (-678del) and IVS12-19G-->A polymorphisms and their haplotypes with the risk of lung cancer in a Korean population. The CASP-8 genotypes were determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects. The distributions of the CASP-8 -678del and IVS12-19G-->A genotypes were not significantly different between the overall lung cancer cases and the controls. When the cases were categorized by tumor histology, however, the IVS12-19 AA genotype and the combined IVS12-19 GA + AA genotype were associated with a significantly decreased risk of small cell carcinoma (SmCC) compared with the IVS12-19 GG genotype [adjusted odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.03-0.64, P = 0.01; and adjusted OR = 0.56, 95% CI = 0.33-0.96, P = 0.03, respectively]. Consistent with the genotyping analyses, the -678del-/IVS12-19A haplotype containing 94% of the IVS12-19A allele in the study population was associated with a significantly decreased risk of SmCC compared with the -678del-/IVS12-19G (adjusted OR = 0.58, 95% CI = 0.36-0.93, P = 0.023, and Pc = 0.046). These findings suggest that the CASP-8 gene may contribute to an inherited predisposition to SmCC of the lung.
"Caspase-9 plays a central role in the execution-phase of cell apoptosis. Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation and may contribute to an individual’s susceptibility to cancer (7). In recent years, few studies have been performed to investigate the associations between effector caspases and cancer risk. "
[Show abstract][Hide abstract] ABSTRACT: Failure of apoptosis is one of the hallmarks of cancer. As an execution-phase caspase, caspase-9 plays a crucial role during apoptosis. To examine whether the Ex5+32 G>A (rs1052576) polymorphism in the CASP-9 gene alters cancer risk, we conducted a comprehensive meta-analysis of 7 case-control studies consisting of a total of 1668 cancer cases and 2294 healthy controls. All studies considered, A allele and A allele carriers of Ex5+32 G>A in the CASP-9 gene had significant associations with cancer risk (OR=0.72, 95% CI, 0.58-0.89, P= 0.003; OR= 0.76, 95% CI, 0.63-0.92, P= 0.004; respectively). In the subgroup analysis, we found that the A allele of Ex5+32 G>A was a protective factor for cancer risk in Chinese and American populations (OR=0.60, 95% CI, 0.44-0.81, P<0.001; OR= 0.80, 95% CI, 0.69-0.94, P= 0.005; respectively). Similarly, we also found positive associations between A allele carriers of Ex5+32 G>A and cancer risk in Chinese and American populations (OR=0.63, 95% CI, 0.44-0.90, P= 0.01; OR= 0.78, 95% CI, 0.62-0.98, P=0.03; respectively). In addition, we identified that A allele and A allele carriers of Ex5+32 G>A may decrease the risk of cancer in the Asian population (OR=0.60, 95% CI, 0.44-0.81, P<0.001; OR= 0.63, 95% CI, 0.44-0.90, P= 0.01; respectively). In conclusion, this meta-analysis demonstrated that A allele and A allele carriers of the Ex5+32 G>A polymorphism in the CASP-9 gene may be protective factors for cancer risk.
Experimental and therapeutic medicine 01/2013; 5(1):175-180. DOI:10.3892/etm.2012.756 · 1.27 Impact Factor
"Subsequent to the initial screening a total of 105 relevant publications were identified. Nineteen studies (20–37) appeared to have met the inclusion criteria and were subjected to further examination. The flow chart of study selection is shown in Fig. 1. "
[Show abstract][Hide abstract] ABSTRACT: Caspase-8 (encoded by the CASP-8 gene) is crucial in generating cell death signals and eliminating potentially malignant cells. Genetic variation in CASP8 may affect susceptibility to cancer. The CASP-8 -652 6N ins/del (rs3834129) polymorphism has been previously reported to influence the progression to several cancers. However, the overall reported studies have shown inconsistent conclusions. In this human genome epidemiology (HuGE) review and meta-analysis, the aim was to identify the association between CASP-8 -652 6N ins/del polymorphism and cancer risk. According to the inclusion criteria, 19 case-control studies with a total of 23,172 cancer cases and 26,532 healthy controls were retrieved. Meta-analysis results showed that the del allele, del allele carrier and ins/del genotype of -652 6N ins/del in the CASP-8 gene were negatively associated with cancer risk (OR=0.91, 95% CI=0.84-0.98, P=0.01; OR=0.88, 95% CI=0.80-0.96, P=0.005; OR=0.91, 95% CI=0.85-0.98, P<0.001; respectively, while no significant correlation was observed between the del/del genotype of -652 6N ins/del and cancer risk (OR=0.89, 95% CI=0.79-1.01, P=0.08). In the subgroup analysis by ethnicity, the meta-analysis indicated that Caucasian populations harboring the del allele, del allele carriers and ins/del genotype had a lower cancer risk (OR=0.96, 95% CI=0.93-1.00, P=0.05; OR=0.86, 95% CI=0.75-1.00, P=0.05; OR=0.91, 95% CI=0.84-0.98, P=0.01; respectively). In addition, a negative association was found between the del allele of -652 6N ins/del in the CASP-8 gene and cancer risk in the Asian population (OR=0.89, 95% CI=0.83-0.97, P=0.005). In conclusion, this meta-analysis suggests that the del allele, del allele carrier and ins/del geno-type of the -652 6N ins/del polymorphism in the CASP-8 gene may be protective factors for cancer risk.
Experimental and therapeutic medicine 10/2012; 4(4):762-770. DOI:10.3892/etm.2012.661 · 1.27 Impact Factor
"Among the 13 polymorphisms in the CASP3, CASP6, CASP7, CASP8, CASP9, and CASP10 genes that have been reported to be potentially functional or otherwise associated with cancer risk [11-16], ten polymorphisms (CASP3rs2705897; CASP6 rs1042891, rs2301717; CASP7 rs2227310, rs11593766; CASP8 rs3769818, rs3834129; CASP9 rs1052571, rs4645978; CASP10 rs13006529) were examined. CASP8 rs1045485 and CASP10 rs13010627 were excluded as they are rare or nonexistent in Asian populations [11,21]. "
[Show abstract][Hide abstract] ABSTRACT: This study analyzed potentially functional polymorphisms in CASPASE (CASP) genes and their impact on the prognosis for Korean colorectal cancer patients.
A total of 397 consecutive patients with curatively resected colorectal adenocarcinoma were enrolled in this study. Genomic DNA from these patients was extracted from fresh colorectal tissue, and the 10 polymorphisms in the CASP3, CASP6, CASP7, CASP8, CASP9, and CASP10 genes were determined using a reverse transcription polymerase chain reaction genotyping assay.
The median patient age was 63 years, and 218 (54.9%) patients had colon cancer, while 179 (45.1%) patients had rectal cancer. Univariate and multivariate survival analysis including pathologic stage, patient age, differentiation, and carcinoembryonic antigen level demonstrated that these polymorphisms were not associated with either disease-free or overall survival.
None of the 10 polymorphisms in the CASP genes investigated in this study was found to be an independent prognostic marker for Korean patients with curatively resected colorectal cancer.
Cancer Research and Treatment 03/2012; 44(1):32-6. DOI:10.4143/crt.2012.44.1.32 · 3.32 Impact Factor
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