Association of CASP8 polymorphisms and cancer susceptibility: A meta-analysis

Hashemi, Mohammad; Aftabi, Sajjad; Moazeni‐Roodi, Abdolkarim; Sarani, Hosna; Wiecheć, Emilia; Ghavami, Saeid

doi:10.1016/j.ejphar.2020.173201

Cited by 20 publications

(10 citation statements)

References 111 publications

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“…Caspase8-rs1045485, also known as D302H, is located in exon 10 of the CASP8 gene. The findings of a recent meta-analysis (pooled analysis of 41 studies) by Hashemi et al showed that rs1045485 variant meaningfully reduced cancer susceptibility and stratified analysis also showed the reduced breast cancer risk in Caucasians, population-and hospital-based studies (Hashemi et al, 2020). Enjuanes et al observed a strong correlation between rs1045485 SNP and decreased risk of chronic lymphocytic leukemia in all statistical models including codominant, dominant and recessive.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features

Barati

Bahari

Asadi

et al. 2022

Asian Pac J Cancer Prev

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Background: Caspases (CASPs) are the main executors of the apoptotic process. Studies to date have shown the role of caspase-8 (CASP8) and caspase-9 (CASP9) in carcinogenesis. Therefore, the aim of this study was to investigate the associations between CASP9-rs4233532, CASP9-rs4646018, and CASP8-rs1045485 gene polymorphisms and non-Hodgkin lymphoma (NHL) susceptibility in an Iranian population-based study. Moreover, it was examined whether such the genotype of these polymorphisms is related with clinicopathological characteristics of NHL. Methods: 175 patients with NHL and 175 age-and sex-matched controls were enrolled in this study. We determined the genotypes of single nucleotide polymorphisms (SNPs) from CASP genes with Tetra ARMS-PCR (Amplification refractory mutation system) method. Results: Statistically significant association were observed between CASP9-rs4646018 and increased risk of NHL under codominant CC, codominant TC, and dominant TC+CC genetic models. Our results showed that the A allele of CASP8-rs1045485 was a protective factor for NHL and GArs1045485 genotype significantly reduced risk of NHL. In contrast, CASP9-rs4233532 was not linked to NHL susceptibility. No relationship was detected between CASP8-rs1045485 and CASP9-rs4233532 and NHL clinicopathological characteristics, however genetic variation in CASP9-rs4646018 was associated with histology, treatment and radio therapy of NHL. Conclusions: Our study presented that the CASP8-rs1045485 and CASP9-rs4646018 polymorphisms could affect the risk of NHL in Iranian populations which was the first report to show the significant relationship between rs1045485, rs4646018 polymorphisms and NHL susceptibility. Replication large-scale case-control studies in different ethnicities are warranted to verify these findings.

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Section: Discussionmentioning

confidence: 99%

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features

Barati

Bahari

Asadi

et al. 2022

Asian Pac J Cancer Prev

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“…Caspase-8 belongs to the cysteine aspartyl protease (caspase) family. Caspases drive apoptosis by cleaving aspartic acid peptide bonds, thus resulting in cell death 17 . Here, we found that caspase-8K14R inhibited malignancy and increased apoptosis rates.…”

Section: Discussionmentioning

confidence: 99%

“…Caspase-8K14R showed higher caspase-8 activity than caspase-8WT (Figure 5A). An important role of caspase-8 is triggering the extrinsic apoptosis pathway when TRAIL binds TRAIL-R [17][18][19] . Thus, we sought to determine the effects of caspase-8K14R on apoptosis after treatment with TRAIL.…”

Section: Caspase-8k14r Is More Sensitive To Trailmediated Apoptosismentioning

confidence: 99%

A causal variant rs3769823 in 2q33.1 involved in apoptosis pathway leading to a decreased risk of non-small cell lung cancer

et al. 2022

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Objective: Although our previous genome-wide association study (GWAS) has identified chromosome 2q33.1 as a susceptibility locus for non-small cell lung cancer (NSCLC), the causal variants remain unclear. The aims of this study were to identify the causal variants in 2q33.1 and to explore their biological functions in NSCLC. Methods: CCK-8, colony formation, EdU incorporation, Transwell, and quantitative real-time polymerase chain reaction assays were applied to examine variant function. The tumor xenograft model was used to examine variant function in vivo. Caspase-8 activity assays, flow cytometry analysis, and co-immunoprecipitation assays were used to explore the molecular mechanism. Results: The missense variant rs3769823 (A > G), which caused the substitution of lysine with arginine at amino acid 14 in caspase-8 (caspase-8K14R), was identified as a potential causal candidate in 2q33.1. Compared with the wild type caspase-8 (caspase-8WT) group, the caspase-8K14R group had higher expression of caspase-8 and cleaved caspase-8. Caspase-8K14R inhibited the proliferation and metastasis of human lung cancer cell lines in vitro. Moreover, caspase-8K14R repressed lung cancer cell growth in vivo. Mechanistically, caspase-8K14R was more sensitive than caspase-8WT to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and showed higher binding of caspase-8 and FADD. Conclusions: These results suggested that rs3769823 is the causal variant in chromosome 2q33.1 and is involved in an apoptosis pathway, leading to a decreased risk of NSCLC. KEYWORDSNon-small cell lung cancer; chromosome 2q33.1; risk; caspase-8; apoptosis

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“…Fritsch et al established that caspase-8 functions as the pyroptotic (17). The CASP8 gene is a critical cancer susceptible gene, as shown by numerous researches examining a variety of tumor forms, such as ovarian cancer, lung, prostate, and breast (18)(19)(20). Soung et al discovered that the CASP8 gene is commonly altered in HCC and that this mutation could result in the loss of the cell death role of CASP8 gene, thereby leading to the occurrence and progression of HCC (21).…”

Section: Discussionmentioning

confidence: 99%

A newly identified pyroptosis-related gene signature for predicting prognosis of patients with hepatocellular cancer

Shen¹,

Jiang²,

Hu³

et al. 2022

Transl Cancer Res TCR

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Background: Hepatocellular carcinoma (HCC) is a very heterogeneous illness, making prognosis prediction a huge problem. Pyroptosis, which has recently been shown to be an inflammatory type of programmed cell death, is involved in HCC. Nevertheless, the role of pyroptosis-related genes in HCC has not been fully elucidated. Thus, this study aimed to construct a prognostic signature based on pyroptosisrelated genes for HCC. Methods:The messenger RNA expression patterns of HCC patients, as well as the accompanying clinical information, were retrieved from The Cancer Genome Atlas (TCGA) database for this research. After differentially expressed pyroptosis-related Gene in tumor and normal groups were identified, Cox regression analyses were performed to construct a prognostic signature which was then assessed through independent prognostic analysis.Results: A signature consisting of four genes (CASP8, GSDME, NOD2, and PLCG1) was constructed to predict overall survival (OS) for HCC. The signature was identified to be independent by the cox regression analysis and obtained the largest area under the receiver operating characteristic (ROC) curve (AUC) was 0.691, 0.628, and 0.632 for survival at 1, 2, and 3 years, respectively.Conclusions: we discovered that the levels of pyroptosis-related genes expression differed across HCC patients and were associated with both survival and prognosis. This suggested that targeting pyroptosis as a treatment strategy for HCC may be a viable option.

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Association of CASP8 polymorphisms and cancer susceptibility: A meta-analysis

Cited by 20 publications

References 111 publications

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features

The Effect of Caspase 8, 9 Gene Polymorphisms on Non-Hodgkin Lymphoma Susceptibility and Clinical/Pathological Features

A causal variant rs3769823 in 2q33.1 involved in apoptosis pathway leading to a decreased risk of non-small cell lung cancer

A newly identified pyroptosis-related gene signature for predicting prognosis of patients with hepatocellular cancer

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