Gene Summary

Gene:FAS; Fas cell surface death receptor
Aliases: APT1, CD95, FAS1, APO-1, FASTM, ALPS1A, TNFRSF6
Summary:The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. [provided by RefSeq, Mar 2011]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:tumor necrosis factor receptor superfamily member 6
Source:NCBIAccessed: 27 February, 2015

Cancer Overview

Research Indicators

Publications Per Year (1990-2015)
Graph generated 27 February 2015 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 27 February, 2015 using data from PubMed, MeSH and CancerIndex

Latest Publications: FAS (cancer-related)

Oh SB, Hwang CJ, Song SY, et al.
Anti-cancer effect of tectochrysin in NSCLC cells through overexpression of death receptor and inactivation of STAT3.
Cancer Lett. 2014; 353(1):95-103 [PubMed] Related Publications
Phenolic compounds (flavonoids and phenolic acid derivatives) are the most important pharmacologically active ingredients, and these compounds could inhibit proliferation of human cancer cells by inducing of apoptotic cell death. Here we focused on the anticancer effects of tectochrysin on human non-small-cell lung cancer (NSCLC) cells and its mechanism of action. We analysed the activity of tectochrysin on NSCLC cells (A549 and NCI-H460) by use of Western blot analysis for major apoptotic proteins and death receptor expression. We also used EMSA for effects on STAT3 DNA binding activity. Tectochrysin (0-80 μM) suppressed the growth of A549 and NCI-H460 lung cancer cells by inducing of apoptotic cell death in a concentration dependent manner. Expression of DR3 and Fas as well as DR downstream pro-apoptotic proteins including cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and Bax were concomitantly increased, but the expression of anti-apoptotic proteins; Bcl-2 was decreased in both cancer cells. In addition, tectochrysin treatment also inhibited phosphorylation of STAT3 in A549 and NCI-H460 cells. However, deletion of DR3 and Fas by small interfering RNA significantly reversed tectochrysin-induced cell growth inhibitory effect as well as down regulation of STAT3 in A549 and NCI-H460 lung cancer cells. Pull down assay and docking model showed interaction of tectochrysin with STAT3. We propose that tectochrysin leads to apoptotic cell death in NSCLC cells through activation of DR3 and Fas expression via inhibition of STAT3 phosphorylation.

Hebbar N, Shrestha-Bhattarai T, Rangnekar VM
Cancer-selective apoptosis by tumor suppressor par-4.
Adv Exp Med Biol. 2014; 818:155-66 [PubMed] Related Publications
Tumor suppressor genes play an important role in preventing neoplastic transformation and maintaining normal tissue homeostasis. Par-4 is one such tumor suppressor which is unique in its ability to selectively induce apoptosis in cancer cells while leaving the normal cells unaffected. The cancer cell specific activity of Par-4 is elicited through intracellular as well as extracellular mechanisms. Intracellularly Par-4 acts through the inhibition of pro-survival pathways and activation of Fas mediated apoptosis whereas extracellular (secreted Par-4) acts by binding to cell surface GRP78 leading to activation of the extrinsic apoptotic pathway. Many studies have highlighted the importance of Par-4 not only in preventing cancer development/recurrence but also as a promising anticancer therapeutic agent.

Zeng Y, Liu J, Yan J, et al.
Letter regarding Wang GQ et al. entitled "associations between Fas/FasL polymorphisms and susceptibility to cervical cancer: a meta-analysis".
Tumour Biol. 2014; 35(8):7293-4 [PubMed] Related Publications

Huang G, Nishimoto K, Yang Y, Kleinerman ES
Participation of the Fas/FasL signaling pathway and the lung microenvironment in the development of osteosarcoma lung metastases.
Adv Exp Med Biol. 2014; 804:203-17 [PubMed] Related Publications
The lungs are the most common site for the metastatic spread of osteosarcoma. Success in using chemotherapy to improve overall survival has reached a plateau. Understanding the biologic properties that permit osteosarcoma cells to grow in the lungs may allow the identification of novel therapeutic approaches-the goal being to alter the tumor cells' expression of cell surface proteins so that there is no longer compatibility with the metastatic niche. We have demonstrated that the Fas Ligand positive (FasL(+)) lung microenvironment eliminates Fas(+) osteosarcoma cells that metastasize to the lungs. Indeed, osteosarcoma lung metastases from patients are Fas(-), similar to what we found in several different mouse models. The Fas(+) cells are cleared from the lungs through apoptosis induced by the Fas signaling pathway following interaction of Fas on the tumor cell surface with the lung FasL. Blocking the Fas signaling pathway interferes with this process, allowing the Fas(+) cells to grow in the lungs. Our investigations show that Fas expression in osteosarcoma cells is regulated epigenetically by the micro-RNA miR-20a, encoded by the miR-17-92 cluster. Our studies support the feasibility of finding agents that can re-induce Fas expression as a novel therapeutic approach to treat osteosarcoma patients with lung metastases. We have identified two such agents, the histone deacetylase inhibitor entinostat and the chemotherapeutic agent gemcitabine (GCB). Aerosol GCB and oral entinostat induce the upregulation of Fas and the regression of established osteosarcoma lung metastases. Aerosol GCB was not effective in the FasL-deficient gld mouse confirming that the lung microenvironment was central to the success of this therapy. Our studies establish the critical role of the lung microenvironment in the metastatic process of osteosarcoma to the lungs and suggest an alternative focus for therapy, that is, incorporating the lung microenvironment as part of the treatment strategy against established osteosarcoma disease in the lungs.

Xu Y, Deng Q, He B, et al.
The diplotype Fas -1377A/-670G as a genetic marker to predict a lower risk of breast cancer in Chinese women.
Tumour Biol. 2014; 35(9):9147-61 [PubMed] Related Publications
This study was designed to reveal the effects of Fas and FasL polymorphisms of interest on breast cancer risk. A total of 439 patients with breast cancer and 439 controls were enrolled in this study. The genotypes Fas -1377G/A, Fas -670A/G, and FasL -844 T/C were detected by MassARRAY. The protein expressions of estrogen receptor, progesterone receptor, and CerbB-2 were determined by immunohistochemistry. Among the 439 patients, Fas mRNA levels in 22 samples of breast cancer and adjacent normal tissues were detected by real-time polymerase chain reaction, and the soluble Fas and Fas ligand concentrations of 180 patients were measured by enzyme-linked immunosorbent assay. The Fas -1377GA, Fas -1377AA, Fas -670AG, Fas -670GG, and FasL -844TC genotypes were associated with a reduced risk of breast cancer. Haplotype analysis indicated that Fas -1377G/-670A was associated with an increased risk of breast cancer, whereas Fas -1377A/-670A was associated with the opposite effect. Furthermore, gene-gene interaction analysis revealed that the Fas -1377GA/AA (-670AG/GG) and FasL -844CC or TC/TT genotypes were associated with a decreased risk of breast cancer. Meanwhile, -1377GG and -670AA genotypes were associated with higher soluble Fas concentrations than other genotypes. We conclude that Fas and FasL polymorphisms can affect breast cancer risk and that Fas polymorphisms are likely to affect breast cancer risk by regulating the soluble Fas concentration.

Meng XW, Koh BD, Zhang JS, et al.
Poly(ADP-ribose) polymerase inhibitors sensitize cancer cells to death receptor-mediated apoptosis by enhancing death receptor expression.
J Biol Chem. 2014; 289(30):20543-58 [PubMed] Article available free on PMC after 25/07/2015 Related Publications
Recombinant human tumor necrosis factor-α-related apoptosis inducing ligand (TRAIL), agonistic monoclonal antibodies to TRAIL receptors, and small molecule TRAIL receptor agonists are in various stages of preclinical and early phase clinical testing as potential anticancer drugs. Accordingly, there is substantial interest in understanding factors that affect sensitivity to these agents. In the present study we observed that the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib and veliparib sensitize the myeloid leukemia cell lines ML-1 and K562, the ovarian cancer line PEO1, non-small cell lung cancer line A549, and a majority of clinical AML isolates, but not normal marrow, to TRAIL. Further analysis demonstrated that PARP inhibitor treatment results in activation of the FAS and TNFRSF10B (death receptor 5 (DR5)) promoters, increased Fas and DR5 mRNA, and elevated cell surface expression of these receptors in sensitized cells. Chromatin immunoprecipitation demonstrated enhanced binding of the transcription factor Sp1 to the TNFRSF10B promoter in the presence of PARP inhibitor. Knockdown of PARP1 or PARP2 (but not PARP3 and PARP4) not only increased expression of Fas and DR5 at the mRNA and protein level, but also recapitulated the sensitizing effects of the PARP inhibition. Conversely, Sp1 knockdown diminished the PARP inhibitor effects. In view of the fact that TRAIL is part of the armamentarium of natural killer cells, these observations identify a new facet of PARP inhibitor action while simultaneously providing the mechanistic underpinnings of a novel therapeutic combination that warrants further investigation.

Verim L, Timirci-Kahraman O, Akbulut H, et al.
Functional genetic variants in apoptosis-associated FAS and FASL genes and risk of bladder cancer in a Turkish population.
In Vivo. 2014 May-Jun; 28(3):397-402 [PubMed] Related Publications
BACKGROUND: The present study aimed to evaluate the role of functional polymorphisms of apoptosis-associated Fatty acid synthase (FAS) and fatty acid synthase ligand (FASL) genes in bladder cancer susceptibility as first presentation in a Turkish population.
PATIENTS AND METHODS: Genotypes of 91 patients with bladder cancer and 101 healthy controls were evaluated for the polymorphism of FAS-1377 G/A and FASL-844 T/C genes by polymerase chain reaction and restriction fragment length polymorphism analysis.
RESULTS: The frequency of the FAS-1377 G allele was significantly higher in patients with bladder cancer compared to controls (p<0.001). A significantly increased risk for developing bladder cancer was found for the group bearing a T allele for FASL-844 compared to the homozygous FASL-844 CC genotype (p=0.027). FAS-1377 GG genotype and FASL-844 T allele were found to be independently associated with an increased risk of bladder cancer. Additionally, gene-gene interaction analysis revealed that the frequency of FAS-1377AA with FASL-844TC was significantly lower in patients with bladder cancer in comparison to those of controls (p<0.001). Extensive studies for gene-gene interaction are still needed.
CONCLUSION: Our study provides new evidence that FAS-1377 G and FASL-844 T alleles may be used as low-penetrant risk factors for bladder cancer development in a Turkish population.

Weiss JM, Subleski JJ, Back T, et al.
Regulatory T cells and myeloid-derived suppressor cells in the tumor microenvironment undergo Fas-dependent cell death during IL-2/αCD40 therapy.
J Immunol. 2014; 192(12):5821-9 [PubMed] Article available free on PMC after 25/07/2015 Related Publications
Fas ligand expression in certain tumors has been proposed to contribute to immunosuppression and poor prognosis. However, immunotherapeutic approaches may elicit the Fas-mediated elimination of immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) within tumors that represent major obstacles for cancer immunotherapy. Previously, we showed that IL-2 and agonistic CD40 Ab (αCD40) elicited synergistic antitumor responses coincident with the efficient removal of Tregs and MDSCs. We demonstrate in this study in two murine tumor models that Treg and MDSC loss within the tumor microenvironment after IL-2/αCD40 occurs through a Fas-dependent cell death pathway. Among tumor-infiltrating leukocytes, CD8(+) T cells, neutrophils, and immature myeloid cells expressed Fas ligand after treatment. Fas was expressed by tumor-associated Tregs and immature myeloid cells, including MDSCs. Tregs and MDSCs in the tumor microenvironment expressed active caspases after IL-2/αCD40 therapy and, in contrast with effector T cells, Tregs significantly downregulated Bcl-2 expression. In contrast, Tregs and MDSCs proliferated and expanded in the spleen after treatment. Adoptive transfer of Fas-deficient Tregs or MDSCs into wild-type, Treg-, or MDSC-depleted hosts resulted in the persistence of Tregs or MDSCs and the loss of antitumor efficacy in response to IL-2/αCD40. These results demonstrate the importance of Fas-mediated Treg/MDSC removal for successful antitumor immunotherapy. Our results suggest that immunotherapeutic strategies that include exploiting Treg and MDSC susceptibility to Fas-mediated apoptosis hold promise for treatment of cancer.

Liu Q, Tan Q, Zheng Y, et al.
Blockade of Fas signaling in breast cancer cells suppresses tumor growth and metastasis via disruption of Fas signaling-initiated cancer-related inflammation.
J Biol Chem. 2014; 289(16):11522-35 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
Mechanisms for cancer-related inflammation remain to be fully elucidated. Non-apoptotic functions of Fas signaling have been proposed to play an important role in promoting tumor progression. It has yet to be determined if targeting Fas signaling can control tumor progression through suppression of cancer-related inflammation. In the current study we found that breast cancer cells with constitutive Fas expression were resistant to apoptosis induction by agonistic anti-Fas antibody (Jo2) ligation or Fas ligand cross-linking. Higher expression of Fas in human breast cancer tissue has been significantly correlated with poorer prognosis in breast cancer patients. To determine whether blockade of Fas signaling in breast cancer could suppress tumor progression, we prepared an orthotopic xenograft mouse model with mammary cancer cells 4T1 and found that blockade of Fas signaling in 4T1 cancer cells markedly reduced tumor growth, inhibited tumor metastasis in vivo, and prolonged survival of tumor-bearing mice. Mechanistically, blockade of Fas signaling in cancer cells significantly decreased systemic or local recruitment of myeloid derived suppressor cells (MDSCs) in vivo. Furthermore, blockade of Fas signaling markedly reduced IL-6, prostaglandin E2 production from breast cancer cells by impairing p-p38, and activity of the NFκB pathway. In addition, administration of a COX-2 inhibitor and anti-IL-6 antibody significantly reduced MDSC accumulation in vivo. Therefore, blockade of Fas signaling can suppress breast cancer progression by inhibiting proinflammatory cytokine production and MDSC accumulation, indicating that Fas signaling-initiated cancer-related inflammation in breast cancer cells may be a potential target for treatment of breast cancer.

Villa-Morales M, Cobos MA, González-Gugel E, et al.
FAS system deregulation in T-cell lymphoblastic lymphoma.
Cell Death Dis. 2014; 5:e1110 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
The acquisition of resistance towards FAS-mediated apoptosis may be required for tumor formation. Tumors from various histological origins exhibit FAS mutations, the most frequent being hematological malignancies. However, data regarding FAS mutations or FAS signaling alterations are still lacking in precursor T-cell lymphoblastic lymphomas (T-LBLs). The available data on acute lymphoblastic leukemia, of precursor origin as well, indicate a low frequency of FAS mutations but often report a serious reduction in FAS-mediated apoptosis as well as chemoresistance, thus suggesting the occurrence of mechanisms able to deregulate the FAS signaling pathway, different from FAS mutation. Our aim at this study was to determine whether FAS-mediated apoptotic signaling is compromised in human T-LBL samples and the mechanisms involved. This study on 26 T-LBL samples confirms that the FAS system is impaired to a wide extent in these tumors, with 57.7% of the cases presenting any alteration of the pathway. A variety of mechanisms seems to be involved in such alteration, in order of frequency the downregulation of FAS, the deregulation of other members of the pathway and the occurrence of mutations at FAS. Considering these results together, it seems plausible to think of a cumulative effect of several alterations in each T-LBL, which in turn may result in FAS/FASLG system deregulation. Since defective FAS signaling may render the T-LBL tumor cells resistant to apoptotic cell death, the correct prognosis, diagnosis and thus the success of anticancer therapy may require such an in-depth knowledge of the complete scenario of FAS-signaling alterations.

Xu Y, He B, Li R, et al.
Association of the polymorphisms in the Fas/FasL promoter regions with cancer susceptibility: a systematic review and meta-analysis of 52 studies.
PLoS One. 2014; 9(3):e90090 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
Fas and its ligand (FasL) play an important role in apoptosis and carcinogenesis. Therefore, the potential association of polymorphisms in the Fas (-670A>G, rs1800682; -1377G>A, rs2234767) and FasL (-844C>T, rs763110) with cancer risk has been widely investigated. However, all the currently available results are not always consistent. In this work, we performed a meta-analysis to further determine whether carriers of the polymorphisms in Fas and FasL of interest could confer an altered susceptibility to cancer. All relevant data were retrieved by PubMed and Web of Science, and 52 eligible studies were chosen for this meta-analysis. There was no association of the Fas -670A>G polymorphism with cancer risk in the pooled data. For the Fas -1377G>A and FasL -844C>T polymorphisms, results revealed that the homozygotes of -1377A and -844C were associated with elevated risk of cancer as a whole. Further stratified analysis indicated markedly increased risk for developing breast cancer, gastric cancer, and esophageal cancer, in particular in Asian population. We conclude that carriers of the Fas-1377A and the FasL -844C are more susceptible to the majority of cancers than non-carriers.

Rai R, Sharma KL, Sharma S, et al.
Death receptor (DR4) haplotypes are associated with increased susceptibility of gallbladder carcinoma in north Indian population.
PLoS One. 2014; 9(2):e90264 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
BACKGROUND AND AIM: Defective apoptosis is a hallmark of cancer development and progression. Death receptors (DR4, FAS) and their ligands (TRAIL, FASL) are thought to mediate the major extrinsic apoptotic pathway in the cell. SNPs in these genes may lead to defective apoptosis. Hence, the present study aimed to investigate the association of functional SNPs of DR4 (rs20575, rs20576 and rs6557634), FAS (rs2234767) and FASL (rs763110) with gallbladder cancer (GBC) risk.
METHODS: This case-control study included 400 GBC and 246 healthy controls (HC). Genotyping was carried out by Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16. Meta-analysis was performed using Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) to systematically summarize the possible association of SNP with cancer risk. Functional prediction of these variants was carried out using Bioinformatics tools (FAST-SNP, F-SNP). False discovery rate (FDR test) was used in multiple comparisons.
RESULTS: The DR4 C rs20575 A rs20576 A rs6557634, G rs20575 A rs20576 G rs6557634 and G rs20575 C rs20576 G rs6557634 haplotypes conferred two-fold increased risk for GBC. Among these, the DR4 C rs20575 A rs20576 A rs6557634 haplotype emerged as main factor influencing GBC susceptibility as the risk was not modulated by gender or gallstone stratification. Our meta-analysis results showed significant association of DR4 rs6557634 with overall cancer risk, GI cancers as well as in Caucasians. We didn't find any association of FAS and FASL SNPs with GBC susceptibility.
CONCLUSIONS: The DR4 haplotype C rs20575 A rs20576 A rs6557634 represents an important factor accounting the patients susceptibility to GBC probably due to decreased apoptosis. However, additional well-designed studies with larger sample size focusing on different ethnicities are required to further validate the results.

Wang X, Xing GH, Fan CC
Association between the FAS rs2234767G/A polymorphism and cancer risk: a systematic review and meta-analysis.
DNA Cell Biol. 2014; 33(5):320-7 [PubMed] Related Publications
Abnormal regulation of apoptosis can lead to carcinogenesis. Single nucleotide polymorphisms in apoptotic genes have been associated with cancer risk, such as the FAS rs2234767G/A polymorphism, which alters transcription of the FAS promoter. Downregulation of FAS, with resultant cellular resistance to death signals, has been found in many cancers. However, the association between the FAS rs2234767G/A polymorphism and cancer risk is still controversial. Here, we performed a meta-analysis including 41 articles (44 case-control studies, 17,814 cases and 24,307 controls) identified from PubMed and Chinese language (CNKI and WanFang) databases related to cancer susceptibility and the FAS rs2234767G/A polymorphism. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the associations. We found that the rs2234767 G-allele was a protective factor for cancer risk (GG vs. AA: OR=0.88, 95% CI=0.79-0.98; GG+GA vs. AA: OR=0.87, 95% CI=0.79-0.96). Similar associations were detected in the "source of control", ethnicity, and cancer type subgroups. Further studies on a larger sample size and considering gene-environment interactions should be conducted to confirm the role of FAS polymorphisms, especially rs2234767G/A, in cancer risk.

Geng P, Li J, Ou J, et al.
Association of Fas -1377 G/A polymorphism with susceptibility to cancer.
PLoS One. 2014; 9(2):e88748 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
BACKGROUND: The relationship between Fas -1377 G/A polymorphism and cancer susceptibility has been implicated in accumulating data. However, the data presented inconsistent results. This study was devised to investigate the association of Fas -1377 G/A polymorphism and cancer susceptibility in a large number of participants.
METHODS: The databases of PubMed, Embase, and Web of Science were searched and a total of 27 case-control studies including 13,355 cases and 16,078 controls were included in this meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the fixed-effects model. Statistical analyses were performed by using Stata software.
RESULTS: The results suggested that Fas -1377 G/A polymorphism was overall associated with cancer susceptibility (additive model: OR, 1.16, 95%CI = 1.06-1.27, Pheterogeneity = 0.381; recessive model: OR, 1.19, 95%CI = 1.10-1.29, Pheterogeneity= 0.137). In the subgroup analysis by cancer type, significantly increased risk was observed in breast cancer (additive model: OR, 1.24, 95%CI = 1.04-1.58, Pheterogeneity = 0.614; recessive model: OR, 1.24, 95%CI = 1.02-1.51, Pheterogeneity = 0.349) and lung cancer (recessive model: OR, 1.25, 95%CI = 1.04-1.49, Pheterogeneity = 0.090). Similarly, elevated cancer risk associated with Fas -1377 G/A polymorphism was revealed in Asians.
CONCLUSIONS: The combined results suggest that Fas -1377 G/A polymorphism might modulate cancer susceptibility in an Asian-specific manner.

Gu D, Du M, Tang C, et al.
Functional polymorphisms in apoptosis pathway genes and survival in patients with gastric cancer.
Environ Mol Mutagen. 2014; 55(5):421-7 [PubMed] Related Publications
The FAS, FAS ligand (FASL), and CASP8 are key regulators for apoptosis and their deregulations play an important role in carcinogenesis. However, the effects of promoter polymorphisms of the FAS, and FASL, and CASP8 genes on the survival of gastric cancer are unknown. In this study, we investigated the association of four polymorphisms (FAS -1377G>A, -670A>G, FASL -844C>T, and CASP8 -652 6N ins>del) with the clinical outcome of 940 gastric cancer patients in a Chinese population. The correlation between genotype and survival outcomes was assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. Our results revealed that individuals with CASP8 -652 6N ins/del+del/del genotypes had a decreased risk of death compared with those with ins/ins genotype (log-rank P=0.005; hazard ratio=0.75, 95% confidence interval=0.62-0.92). The protective effect of the del allele was further confirmed in subgroups of patients with tumor size ≤ 5 cm (0.66, 0.50-0.86) and T2 depth invasion (0.59, 0.37-0.94), but no significant association was observed in the subgroups of lymph node metastasis (0.67, 0.47-0.97), and distance metastasis (0.73, 0.60-0.90). Our findings suggest that, if validated in different independent populations, the CASP8 -652 6N ins>del polymorphism may serve as a promising genetic marker for gastric cancer prognosis.

Thurner EM, Krenn-Pilko S, Langsenlehner U, et al.
Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy.
Strahlenther Onkol. 2014; 190(3):304-9 [PubMed] Related Publications
BACKGROUND AND PURPOSE: Fas ligand (FASL) triggers apoptotic cell death by cross-linking with its receptor FAS, and after irradiation, expression of FAS and FASL is increased. In the present study, we investigated the association between common polymorphisms in the genes for FAS and FASL and the risk of late side effects after radiotherapy for prostate cancer.
PATIENTS AND METHODS: The role of FAS (- 1377G > A, rs2234767 and - 670A > G, rs1800682) and FASL (- 844C > T, rs763110) gene polymorphisms in the development of high-grade late rectal and/or urinary toxicity (defined as late toxicity EORTC/RTOG grade ≥ 2) was analyzed in 607 prostate cancer patients treated with radiotherapy. DNA was isolated and the selected polymorphisms were determined by 5'-nuclease (TaqMan) assays.
RESULTS: After a median follow-up time of 82 months, high-grade late rectal and/or urinary toxicity was observed in 175 patients (29.7 %). Univariate analysis revealed a significantly decreased risk of high-grade late toxicity in carriers of the FASL - 844T allele. After adjusting for covariates, patients harboring at least one - 844T allele (CT or TT genotype) remained at decreased risk of high-grade late toxicity compared with patients harboring the CC genotype [hazard ratio (HR) 0.585, 95 %CI 0.39-0.878; p = 0.010]. For patients with the - 844TT genotype, the HR was 0.404 (95 %CI 0.171-0.956; p = 0.039) in multivariate analysis. No significant associations were found for the remaining polymorphisms analyzed.
CONCLUSIONS: These results provide the first evidence that the presence of the FASL - 844T variant allele may have a protective effect against the development of high-grade late rectal and/or urinary side effects after prostate cancer radiotherapy.

Wang GQ, Bao L, Zhao XX, et al.
Associations between Fas/FasL polymorphisms and susceptibility to cervical cancer: a meta-analysis.
Tumour Biol. 2014; 35(5):4107-12 [PubMed] Related Publications
UNLABELLED: Genetic polymorphisms in the Fas/Fas ligand (FasL) gene were proposed to be associated with susceptibility to cervical cancer, but previous studies reported controversial findings. We performed a meta-analysis to assess the associations between Fas/FasL polymorphisms and susceptibility to cervical cancer. We carried out a literature search in PubMed and Embase databases for studies on the associations between Fas/FasL polymorphisms and susceptibility to cervical cancer. The associations were assessed by odds ratio (OR) together with its 95% confidence intervals (CIs). Eleven individual studies with a total of 6,919 subjects were finally included into the meta-analysis. Overall, there was no association between Fas 1377G > A polymorphism and susceptibility to cervical cancer (A vs. G: OR = 0.99, 95% CI 0.88-1.12, P = 0.91; AA vs. GG: OR = 1.00, 95% CI 0.76-1.32, P = 0.99; AA/GA vs. GG: OR = 0.95, 95% CI 0.81-1.12, P = 0.54; AA vs.
GG/GA: OR = 1.11, 95% CI 0.85-1.43, P = 0.45). In addition, there was also no association between FasL 844 T > C polymorphism and susceptibility to cervical cancer (C vs. T: OR = 1.12, 95% CI 0.91-1.36, P = 0.28; CC vs. TT: OR = 1.17, 95% CI 0.90-1.51, P = 0.24; CC/TC vs. TT: OR = 1.13, 95% CI 0.92-1.39, P = 0.24; CC vs.
TT/TC: OR = 1.11, 95% CI 0.83-1.50, P = 0.47). In subgroup analysis by ethnicity, there were also no associations between Fas/FasL polymorphisms and susceptibility to cervical cancer in Asians and Africans. In conclusion, Fas 1377G > A polymorphism and FasL 844 T > C polymorphism are both not associated with susceptibility to cervical cancer.

Verma RK, Gunda V, Pawar SC, Sudhakar YA
Extra cellular matrix derived metabolite regulates angiogenesis by FasL mediated apoptosis.
PLoS One. 2013; 8(12):e80555 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
OBJECT: Antiangiogenic treatments are beginning to give promising outcomes in many vascular diseases including tumor angiogenesis. In this current study the antiangiogenic and pro-apoptotic actions of α1(IV)NC1 and its N- and C- peptides α1S1(IV)NC1, α1S2(IV)NC1 were investigated in-vitro and in-vivo.
STUDY METHOD: Endothelial cells (ECs) were treated with α1(IV)NC1, α1S1(IV)NC1, α1S2(IV)NC1 and in-vitro proliferation, migration, tube formation and apoptotic assays were executed. FasL, Fas, Caspase-8, -3 and PARP activations were studied using immunoblotting analysis using specific antibodies. Also the in-vivo antiangiogenic and pro-apoptotic effects were tested using α1(IV)NC1 in a mice model.
RESULTS: Like α1(IV)NC1, its N- and C- terminal α1S2(IV)NC1 and α1S1(IV)NC1 domains posses anti-proliferative, pro-apoptotic activity and inhibit ECs migration and tube formation in-vitro. Both α1S1(IV)NC1 and α1S2(IV)NC1 domains promote apoptosis by activating FasL and down stream apoptotic events including activation of caspase-8, -3 and PARP cleavage in a dose dependent manner in-vitro in ECs. Tumors in mice showed apoptotic TUNEL positive microvasculature upon α1(IV)NC1 treatment, indicating inhibition of tumor angiogenesis and tumor growth. Further, the antitumor activity of α1(IV)NC1 was abrogated when caspase-3 inhibitor was used. These results conform additional properties of α1(IV)NC1 as an endogenous angioinhibitor that induces apoptosis in-vitro and in-vivo by activating FasL mediated caspase-3.
SIGNIFICANCE: α1(IV)NC1 and its N- and C- terminal α1S1(IV)NC1 and α1S2(IV)NC1 domains also posses pro-apoptotic and angioinhibitory activity in-vitro and in-vivo. α1(IV)NC1 regulates tumor angiogenesis by activating FasL mediated apoptosis in-vitro and in-vivo. These results demonstrate that α1(IV)NC1 and its peptides inhibit neo-vascular diseases.

Yamada N, Noguchi S, Kumazaki M, et al.
Epigenetic regulation of microRNA-128a expression contributes to the apoptosis-resistance of human T-cell leukaemia jurkat cells by modulating expression of fas-associated protein with death domain (FADD).
Biochim Biophys Acta. 2014; 1843(3):590-602 [PubMed] Related Publications
Increased expression of miR-128a is often observed in acute lymphoblastic leukaemia (ALL) compared with its expression in acute myeloid leukaemia (AML). The objective of this study was to investigate the role of miR-128a, especially that in the Fas-signalling pathway, in T-cell leukaemia cells. The role of miR-128a in Fas-mediated apoptosis was examined by using Fas-activating antibody (CH-11)-susceptible Jurkat cells and -resistant Jurkat/R cells. Whereas ectopic expression of miR-128a conferred Fas-resistance on Jurkat cells by directly targeting Fas-associated protein with death domain (FADD), antagonizing miR-128a expression sensitized Jurkat/R cells to the Fas-mediated apoptosis through derepression of FADD expression. Myeloid leukaemia HL60 and K562 cells were also CH-11-resistant, sharing a similar resistant mechanism with Jurkat/R cells. Furthermore, CH-11 induced demethylation of the promoter region of miR-128a with resultant up-regulation of miR-128a expression in Jurkat/R cells, which was shown to be a mechanism for the resistance ofJurkat/R cells to Fas-mediated apoptosis. Our results indicate that the induction of miR-128a expression by DNA demethylation is a novel mechanism of resistance to Fas-mediated apoptosis.

Wang Z, Gu J, Nie W, et al.
Quantitative assessment of the association between three polymorphisms in FAS and FASL gene and breast cancer risk.
Tumour Biol. 2014; 35(4):3035-9 [PubMed] Related Publications
FAS and FAS ligand (FASL) play crucial roles in apoptotic signaling, and deregulation of this pathway may facilitate carcinogenesis. Studies on the association between the FAS/FASL polymorphisms (FAS-1377G/A rs2234767, FAS-670A/G rs1800682, and FASL-844C/T rs763110) and breast cancer risk have reported inconsistent results. Therefore, to characterize the relationship between those polymorphisms and breast cancer risk, we undertook a meta-analysis of those studies. Several electronic databases were searched for articles on the FAS/FASL polymorphisms and breast cancer risk. The genotype data were extracted; pooled odds ratios (OR) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Five studies were eligible for our meta-analysis. Overall, we observed significant associations of the FAS-1377G/A polymorphism with breast cancer susceptibility (AG vs. GG: OR = 1.15, 95% CI 1.02-1.30; AA vs. GG: OR = 1.39, 95% CI 1.12-1.72; AG/AA vs. GG: OR = 1.18, 95% CI, 1.16-1.32; A vs. G: OR = 1.16, 95% CI 1.06-1.26), but we did not observe significant association of the Fas-670A/G and FasL-844C/T polymorphisms with breast cancer risk. In the subgroup analysis, we observed that the FAS-1377G/A and FASL-844C/T polymorphisms were associated with breast cancer risk in Chinese but not Whites; we still did not observed association of the FAS-670A/G polymorphism with breast cancer risk. Our meta-analysis revealed that FAS-1377G>A polymorphism was associated with an increased risk of breast cancer. FASL-844C>T polymorphism might be associated with a reduced breast cancer risk in Chinese. However, FAS-670A/G had no any effect on breast carcinogenesis.

Sangaletti S, Tripodo C, Vitali C, et al.
Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma.
Cancer Discov. 2014; 4(1):110-29 [PubMed] Related Publications
Altered expression of matricellular proteins can become pathogenic in the presence of persistent perturbations in tissue homeostasis. Here, we show that autoimmunity associated with Fas mutation was exacerbated and transitioned to lymphomagenesis in the absence of SPARC (secreted protein acidic rich in cysteine). The absence of SPARC resulted in defective collagen assembly, with uneven compartmentalization of lymphoid and myeloid populations within secondary lymphoid organs (SLO), and faulty delivery of inhibitory signals from the extracellular matrix. These conditions promoted aberrant interactions between neutrophil extracellular traps and CD5(+) B cells, which underwent malignant transformation due to defective apoptosis under the pressure of neutrophil-derived trophic factors and NF-κB activation. Furthermore, this model of defective stromal remodeling during lymphomagenesis correlates with human lymphomas arising in a SPARC-defective environment, which is prototypical of CD5(+) B-cell chronic lymphocytic leukemia (CLL).

Zeng J, Fang Y, Li P
FAS-1377 A/G polymorphism in breast cancer: a meta-analysis.
Tumour Biol. 2014; 35(3):2575-81 [PubMed] Related Publications
FAS is a cell surface receptor involved in apoptotic signaling in many cell types including cells of the immune system. The -1377 A/G polymorphism of FAS gene has been detected in breast cancer. However, the published evidence regarding the -1377 A/G polymorphism and breast cancer risk has generated controversial results. We performed a meta-analysis of five case-control association studies totaling to 5,995 study subjects including 2,905 cases and 3,090 controls. The combined odd ratios (ORs) with its 95% CIs were used to assess the association of the -1377 A/G polymorphism correlated with breast cancer susceptibility with the fixed-effects model. The combined results showed significantly increased risk associated with the -1377 A/G polymorphism under AA vs. GG genetic model (OR = 1.28, 95% CI = 1.04-1.58; heterogeneity test: P = 0.614, I (2)  = 0.0%), AA vs. GA + GG genetic model (OR = 1.24, 95 CI = 1.02-1.51; heterogeneity test: P = 0.349, I (2)  = 10.0%), and allele model A vs. G (OR = 1.10, 95%CI = 1.02-1.20; heterogeneity test: P = 0.422, I (2)  = 0.0%). Similarly, significant association was found in Asians. In stratified analyses by control source, a higher risk was indicated in the hospital-based studies rather than the population-based studies. This meta-analysis suggests that the -1377 A/G polymorphism is likely to be associated with the risk of breast cancer, especially the A allele in Asians.

Zhang Y, Tong S, Guan L, et al.
CD95 rs1800682 polymorphism and cervical cancer risk: evidence from a meta-analysis.
Tumour Biol. 2014; 35(3):1785-90 [PubMed] Related Publications
CD95 is the first death receptor identified and characterized in recent years, and it plays important roles in the molecular network regulating cell death and survival. CD95 rs1800682 polymorphism is a common genetic polymorphism identified in the CD95 gene. Many publications evaluated the association between CD95 rs1800682 polymorphism and cervical cancer risk, but the association remained inconclusive. To provide a more precise estimate on the association, a meta-analysis was carried out. The association between CD95 rs1800682 polymorphism and cervical cancer risk was assessed by calculating the pooled odds ratio (OR) with its 95% confidence intervals (95% CI). On the basis of our inclusion criteria, ten studies with a total of 5,481 individuals were included into the meta-analysis. There was obvious heterogeneity among the included studies. Meta-analysis of the ten studies suggested that there was no association between CD95 rs1800682 polymorphism and cervical cancer risk under all four genetic models (allele model: OR = 1.05, 95% CI 0.92-1.18, P = 0.478; homozygous model: OR = 1.08, 95% CI 0.83-1.41, P = 0.550; dominant model: OR = 1.12, 95% CI 0.88-1.42, P = 0.347; recessive model: OR = 1.00, 95% CI 0.76-1.31, P = 0.978). Subgroup analysis by ethnicity suggested that there was no association between CD95 rs1800682 polymorphism and cervical cancer risk in Asians, Caucasians, and Africans. Thus, the meta-analysis suggests that CD95 rs1800682 polymorphism is not associated with cervical cancer risk.

Dalan AB, Timirci-Kahraman O, Turan S, et al.
Association between FAS and FASL genetic variants and risk of primary brain tumor.
Int J Neurosci. 2014; 124(6):443-9 [PubMed] Related Publications
The purpose of this study was to investigate whether functional polymorphisms of apoptosis pathway genes FAS and FASL are associated with the development of primary brain tumors. The study constituted 83 patients with primary brain tumor and 108 healthy individuals. In the present case-control study, the primary brain tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS -1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm the genotyping, results were examined by DNA sequencing method. Our results were analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly lower in meningioma and glioma patients compared to controls (p = 0.023; p = 0.001, respectively). Multivariate logistic regression analysis revealed that FAS -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR = 0.092, 95% CI: 0.012-0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI: 0.007-0.428, p = 0.006 for gliomas). However, there was no significant differences in FASL -844 T/C genotype frequencies between patients with primary brain tumors and controls (p > 0.05). In this study, combined genotypes were evaluated for association with primary brain tumors. Combined genotype analysis showed that the frequencies of AATC and AACC were significantly lower in glioma patients in comparison with those of controls (p = 0.023; p = 0.022, respectively). This study provides the first evidence that FAS -1377 AA genotype may have a protective effect on the developing primary brain tumor in a Turkish population.

Zhong-Xing Z, Yuan-Yuan M, Hai Zhen M, et al.
FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls.
PLoS One. 2013; 8(8):e73700 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
BACKGROUND AND OBJECTIVES: Disruption of apoptosis has been implicated in carcinogenesis. Specifically, various single-nucleotide polymorphisms (SNPs) in apoptotic genes, such as FAS-1377 G/A SNP, have been associated with cancer risk. FAS-1377 G/A SNP has been shown to alter FAS gene promoter transcriptional activity. Down-regulation of FAS and cell death resistance is key to many cancers, but an association between FAS-1377 G/A SNP and cancer risk is uncertain. Therefore, we conducted a meta-analysis of the current literature to clarify this relationship.
METHODOLOGY/PRINCIPAL FINDINGS: From PubMed and Chinese language (CNKI and WanFang) databases, we located articles published up to March 5, 2013, obtaining 44 case-control studies from 41 different articles containing 17,858 cases and 24,311 controls based on search criteria for cancer susceptibility related to the FAS gene -1377 G/A SNP. Odds ratios (ORs) and 95% confidence intervals (CI) revealed association strengths. Data show that the -1377 G allele was protective against cancer risk. Similar associations were detected in "source of control," ethnicity and cancer type subgroups. Lower cancer risk was found in both smokers with a GG+GA genotype and in non-smokers with the GG+GA genotype, when compared to smokers and nonsmokers with the AA genotype. Males carrying the -1377G allele (GG+GA) had lower cancer incidence than those with the AA genotype. Individuals who carried both FAS-1377(GG+GA)/FASL-844(TT+TC) genotypes appeared to have lower risk of cancer than those who carried both FAS-1377 AA/FASL-844 CC genotypes.
CONCLUSIONS/SIGNIFICANCE: The FAS-1377 G/A SNP may decrease cancer risk. Studies with larger samples to study gene-environment interactions are warranted to understand the role of FAS gene polymorphisms, especially -1377 G/A SNP, in cancer risk.

Li K, Li W, Zou H, Zhao L
Association between FAS 1377G>A polymorphism and breast cancer susceptibility: a meta-analysis.
Tumour Biol. 2014; 35(1):351-6 [PubMed] Related Publications
Published studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility were inconclusive. To derive a more precise assessment of the association, a meta-analysis of published studies was performed. PubMed, Embase, and Web of Science were searched for eligible studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility. Five studies with a total of 2,905 cases and 3,090 controls were included into the meta-analysis. Overall, FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer (for AA versus GG: odds ratio (OR) = 1.39, 95% confidence interval (95% CI) 1.12-1.72, P = 0.003; for AA/GA versus GG: OR = 1.18, 95% CI 1.06-1.32, P = 0.004; for AA versus GG/GA: OR = 1.28, 95% CI 1.05-1.56, P = 0.015). Subgroup analysis by ethnicity found that FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer in Asians (for AA versus GG: OR = 1.48, 95% CI 1.16-1.89, P = 0.001; for AA/GA versus GG: OR = 1.24, 95% CI 1.06-1.46, P = 0.008; for AA versus GG/GA: OR = 1.35, 95% CI 1.08-1.69, P = 0.008), but the association was not found in Caucasians. Therefore, the findings of the meta-analysis suggest that FAS 1377G>A polymorphism is significantly associated with increased susceptibility to breast cancer in Asians.

Han W, Zhou Y, Zhong R, et al.
Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population.
PLoS One. 2013; 8(8):e71656 [PubMed] Article available free on PMC after 18/04/2015 Related Publications
The FAS and FASL system plays a substantial role in apoptosis and immune escape of cells. Three polymorphisms located in the promoter regions of FAS (-1377G/A and -670A/G) and FASL (-844T/C) have been shown to alter the transcriptional activity of the genes, respectively. This study was conducted to evaluate the effects of these polymorphisms on the susceptibility of neuroblastoma in the Chinese population. A total of 203 patients with neuroblastoma and 411 controls were recruited in this case-control study. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was applied for genotyping. Unconditional logistic regression was used to estimate cancer risk by calculating odds ratios (ORs) and their 95% confidence intervals (95% CIs). It was observed that significantly increased risks of neuroblastoma associated with FAS -1377G/A and FASL -844T/C polymorphisms, with ORs equal to 1.55 (95% CI, 1.10-2.20) for FAS -1377 A allele and 2.90 (95% CI, 2.04-4.12) for FASL -844CC genotype carriers compared with non-carriers, respectively. However, no association was found between the polymorphisms of FAS -670A/G and risk of neuroblastoma. In addition, the cumulative effect of FAS and FASL polymorphisms on risk of neuroblastoma was observed (P for trend = 2.502×10(-10)), with OR for the carriers of both FAS -1377A allele and FASL -844CC genotypes equaled to 3.95 (95% CI, 2.40-6.51). This work reveals that polymorphisms of FAS -1377G/A and FASL -844T/C but not FAS -670A/G are associated with risk of neuroblastoma in Chinese. These findings support the hypothesis that genetic polymorphism in FAS/FASL death system may influence individual susceptibility to neuroblastoma.

Lima L, Ferreira JA, Tavares A, et al.
FASL polymorphism is associated with response to bacillus Calmette-Guérin immunotherapy in bladder cancer.
Urol Oncol. 2014; 32(1):44.e1-7 [PubMed] Related Publications
OBJECTIVE: Deregulation of FAS/FASL system may lead to immune escape and influence bacillus Calmette-Guérin (BCG) immunotherapy outcome, which is currently the gold standard adjuvant treatment for high-risk non-muscle invasive bladder tumors. Among other events, functional promoter polymorphisms of FAS and FASL genes may alter their transcriptional activity. Therefore, we aim to evaluate the role of FAS and FASL polymorphisms in the context of BCG therapy, envisaging the validation of these biomarkers to predict response.
PATIENTS AND METHODS: DNA extracted from peripheral blood from 125 patients with bladder cancer treated with BCG therapy was analyzed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism for FAS-670 A/G and FASL-844 T/C polymorphisms. FASL mRNA expression was analyzed by real-time Polymerase Chain Reaction.
RESULTS: Carriers of FASL-844 CC genotype present a decreased recurrence-free survival after BCG treatment when compared with FASL-844 T allele carriers (mean 71.5 vs. 97.8 months, P = 0.030) and have an increased risk of BCG treatment failure (Hazard Ratio = 1.922; 95% Confidence Interval: [1.064-3.471]; P = 0.030). Multivariate analysis shows that FASL-844 T/C and therapeutics scheme are independent predictive markers of recurrence after treatment. The evaluation of FASL gene mRNA levels demonstrated that patients carrying FASL-844 CC genotype had higher FASL expression in bladder tumors (P = 0.0027). Higher FASL levels were also associated with an increased risk of recurrence after BCG treatment (Hazard Ratio = 2.833; 95% Confidence Interval: [1.012-7.929]; P = 0.047). FAS-670 A/G polymorphism analysis did not reveal any association with BCG therapy outcome.
CONCLUSIONS: Our results suggest that analysis of FASL-844 T/C, but not FAS-670 A/G polymorphisms, may be used as a predictive marker of response to BCG immunotherapy.

Zheng H, Li W, Wang Y, et al.
miR-23a inhibits E-cadherin expression and is regulated by AP-1 and NFAT4 complex during Fas-induced EMT in gastrointestinal cancer.
Carcinogenesis. 2014; 35(1):173-83 [PubMed] Related Publications
Fas signaling has been shown to induce the epithelial-mesenchymal transition (EMT) to promote gastrointestinal (GI) cancer metastasis, but the involvement of microRNA in this mechanism remains unknown. We found that Fas ligand (FasL) treatment inhibited E-cadherin expression and promoted cell invasion by upregulation of miR-23a, but overexpression of the miR-23a inhibitor could partially block this activity. FasL-induced extracellular signal-regulated kinase/mitogen-activated protein kinase signaling activated the activator protein 1 (AP-1) complex and repressed glycogen synthase kinase-3β activity, which contributed to nuclear translocation of AP-1 and nuclear factor of activated T cells (NFAT4). Nuclear accumulation and interaction of AP-1 and NFAT4 and subsequent binding to the miR-23a promoter led to increased miR-23a expression. Inhibition of Fas signaling by downregulation of the Fas receptor led to a decrease in miR-23a expression and cell invasion ability in vivo and in vitro, as well as an increase in E-cadherin. Evaluation of human GI precancerous and cancer specimens showed that the expression of FasL and miR-23a increased, whereas the expression of E-cadherin decreased during GI cancer progression. A significant correlation was noted between any two of these three molecules. An EMT phenotype was shown to correlate with an advanced cancer stage and worse prognosis. Taken together, our results show that miR-23a participates in the mechanism of the FasL-induced EMT process and may serve as a potential therapeutic target for cancer metastasis.

Shen J, Sun NX
Association between FAS A670G polymorphism and susceptibility to cervical cancer: evidence from a meta-analysis.
Tumour Biol. 2013; 34(6):3443-8 [PubMed] Related Publications
Previous studies published to evaluate the association between FAS A670G polymorphism and susceptibility to cervical cancer provided conflicting findings. A meta-analysis of published case-control studies was performed to get a comprehensive evidence for the possible association. We searched in PubMed and Wanfang databases for eligible studies published before February 10, 2013. The odds ratio (OR) with 95% confidence interval (95% CI) was used to evaluate the association. Ten studies with a total of 4,904 participants were finally included into the meta-analysis. Overall, there was no obvious association between FAS A670G polymorphism and susceptibility to cervical cancer under all four genetic models (G versus A: OR = 0.97, 95% CI 0.84-1.11, P = 0.64; GG versus AA: OR = 0.92, 95% CI 0.69-1.24, P = 0.60; GG/AG versus AA: OR = 0.99, 95% CI 0.77-1.26, P = 0.92; GG versus AA/AG: OR = 0.92; 95% CI 0.68-1.25, P = 0.59). Subgroup analyses by ethnicity further showed that there was no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians. There was no risk of publication bias. In summary, the meta-analysis suggests that there is no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians.

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