Caspase 8 and caspase 9 gene polymorphisms and susceptibility to gastric cancer

Abstract

Background Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association of CASP8 and CASP9 gene polymorphisms with gastric cancer (GC) susceptibility. Methods We undertook a case-control study of 88 GC cases and 480 controls to investigate the association between CASP8 -652 6N ins/del and CASP9 -1263 A[G polymorphisms and GC susceptibility by a polymerase chain reaction (PCR)-restriction fragment length polymorphism method. Results CASP8 -652 6N ins/del polymorphism and CASP9 -1263 GG genotype were observed to be significantly associated with a reduced risk of GC. No significant association was observed between CASP8 -652 6N ins/del and CASP9 -1263 A[G polymorphisms and tumor characteristics. However, both CASP8 del/del and CASP9 -1263 GG genotypes were associated with increased overall survival in GC patients. Conclusions The CASP8 -652 6N ins/del and the CASP9 -1263 A[G polymorphisms were observed to play a protective role in GC predisposition.

A Meta-Analysis of Caspase 9 Polymorphisms in Promoter and Exon Sequence on Cancer Susceptibility

“…A total of 9 studies [6], [8], [11], [13], [15]–[19] involving 2,390 cases and 3,138 controls were ultimately analyzed for CASP9 rs4645978, six studies [7], [10], [12], [14], [20], [21] involving 1,002 cases and 1,401 controls for rs1052576 and two studies [6], [8] for rs4645981. As for CASP9 rs4645978, there were six subjects of Caucasians [11], [13], [15]–[18] and three subjects of Asians [6], [8], [19]. For rs1052576, there were four groups of Asians [7], [10], [12], [14] and two of Mix [20], [21].…”

“…It is identified some of these SNPs in the promoter or exon sequence of CASP9 as potential biomarkers [eg. −1263A>G (rs4645978), −712C>T (rs4645981) and Ex5+32G.>A (rs1052576)], which can modulate susceptibility to cancer, such as those that occur in the lung [6], [7], [8], esophagus [9], stomach [10], [11], colorectal [12], [13], liver [14], pancreas [15], prostate [16], [17], bladder [18], thyroid [19] and hemopoietic system [20], [21]. However, the observed associations of these studies were inconsistent and a single study may be too underpowered to detect the effect of the gene polymorphism on cancer, especially when the sample size is relatively small.…”

CASP-9 gene functional polymorphisms and cancer risk: A large-scale association study plus meta-analysis

“…However, Catchpoole and Lock (2001) found that CASP-9 is also strongly associated with neuroblastoma. Liamarkopoulos et al (2011) confirmed that CASP-9 genetic polymorphisms influence the risk of gastric cancer. Moreover, Choi et al (2012) demonstrated CASP-9 involvement in the pathogenesis of lung cancer.…”

Bi-directional PCR allele-specific amplification (bi-PASA) for detection of caspase-8 −652 6N ins/del promoter polymorphism (rs3834129) in breast cancer

“…Furthermore, a number of studies have established an association between CASP8 −652 6N del polymorphism and lower risk of predisposition to epithelial ovarian cancer (EOC) (Ma et al, 2011), gastric cancer (GC) (Liamarkopoulos et al, 2011), renal cell carcinoma (RCC) (Zhu et al, 2010), gallbladder cancer (GBC) (Srivastava et al, 2010), and bladder cancer (Wang et al, 2009). Similarly, the meta-analysis of Yin et al (2010) provided evidence regarding the association between the CASP8 −652 6N del variant and reduced cancer risks, and also concerning the potential role of this del variant as a cancer biomarker.…”

“…It is well documented that a sixnucleotide deletion polymorphism (−652 6N del) in the promoter of CASP8 abolishes a binding site for the transcriptional activator 1 (Sp1), resulting in a decreased expression of the CASP8 protein in lymphocytes and lower CASP8 activity and activation-induced cell death of T lymphocytes (Yang et al, 2008). This deletion variants were found to have a protection against several types of cancers (Liamarkopoulos et al, 2011;Ma et al, 2011;Sergentanis and Economopoulos, 2010;Sun et al, 2007;Wang et al, 2009). However, other studies have found no correlation between CASP8 −652 6N ins/del and the risk of several cancers (Chatterjee et al, 2011;Frank et al, 2008;Liu et al, 2010;Wang et al, 2011).…”