CASP8 SNP D302H (rs1045485) Is Associated with Worse Survival in MYCN-Amplified Neuroblastoma Patients

Rihani, Ali; Wilde, Bram De; Zeka, Fjorabla; Laureys, Geneviève; Francotte, Nadine; Tonini, Gian Paolo; Coco, Simona; Versteeg, Rogier; Noguera, Rosa; Schulte, Johannes H.; Eggert, Angelika; Stallings, Raymond L.; Speleman, Franki; Vandesompele, Jo; Maerken, Tom Van

doi:10.1371/journal.pone.0114696

Cited by 19 publications

(24 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the polymorphic sites of CASP8, rs3834129 (-652, 6N ins/del) polymorphism, a six-nucleotide insertion (I)/deletion (D) variant, has been functionally identified to lead to down-regulation of the mRNA of CASP8 (18). Caspase-8 single nucleotide polymorphisms are reported to be genomic markers for the prediction of the personal risk for several types of cancers such as that of the digestive tract (19,20), breast (21)(22)(23), prostate (24), lung (25) and bladder (26), and neuroblastoma (27). Little is known about the role of CASP8 polymorphisms in oral cancer.…”

mentioning

confidence: 99%

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan

Shih

Tsai

Sun

et al. 2019

In Vivo

View full text Add to dashboard Cite

Background/Aim: Recently, mounting evidence has shown that caspase-8 (CASP8) rs3834129 (-652, 6N insertion/deletion) polymorphism may serve as a genetic biomarker for personal risk of various cancer types. The contribution of CASP8 rs3834129 polymorphism has been investigated in several oral cancer populations, but not in Taiwan. This study investigated the role of CASP8 rs3834129 polymorphism on oral risk in Taiwan. Materials and Methods: CASP8 rs3834129 polymorphic genotypes were determined and their associations with oral cancer risk were investigated among 788 patients with oral cancer and 956 age-and gender-matched healthy controls via polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) methodology. In addition, the interaction of CASP8 rs3834129 genotype with personal behavior and clinicopathological features were also examined. Results: The frequencies of II, ID and DD genotypes for CASP8 rs3834129 were 57.5, 36.5 and 6.0% in the patient group and 54.0, 39.0 and 7.0% in the healthy control group, respectively (p for trend=0.3052), genotypes were not significantly differentially distributed between the two groups. The comparisons in allelic frequency distribution also supported the findings that the D variant allele may not serve as a determinant of risk for oral cancer. There was no interaction of CASP8 rs3834129 genotype with age, gender, smoking, alcohol or betel quid consumption in regard to oral cancer risk. Conclusion: Our results indicate that the caspase-8 genotype does not appear to play a direct role in personal susceptibility to oral cancer in Taiwan. Oral cancer is the eighth most commonly diagnosed cancer among men in the world, and about twice more prevalent than among women in the world (1). In Taiwan, the incidence and mortality of oral cancer has occupied the fourth and fifth places among the common cancer types for many years (2), and its high incidence has been proposed to be closely associated with the combinative effects of smoking, alcoholism and, betel quid chewing in addition to genetic factors (3-6). However, the definitive genomic etiology of oral cancer remains largely unknown. In Taiwan, although several useful biomarkers for early detection of oral cancer have been revealed (7-13), the mechanisms underlying them are largely unknown and practical genomic markers for clinical use are still in urgent need. Noticeably, Taiwan has over of the highest densities worldwide of patients with oral cancer. Apoptosis is a bio-essential mechanism for altering the morphology, and controlling the death rate of a stable population (14). In the literature, mounting evidence has shown loss of homeostasis of the apoptosis pathway to be associated with the development of oral cancer (15), and 1151 This article is freely accessible online.

show abstract

mentioning

confidence: 99%

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan

Shih

Tsai

Sun

et al. 2019

In Vivo

View full text Add to dashboard Cite

show abstract

“…However, our data are in accordance with a recent pilot investigation, reporting, albeit with borderline statistical significance, a negative prognostic impact of the CASP8 -652 6N Del allele for colorectal cancer patients [ 19 ]. Complementarily, in a very recent approach, CASP8 302His was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors [ 18 ]. Apoptosis, with caspase 8 as one of its key regulators, is not only involved in AICD of antitumor T lymphocytes, but also constitutes an important defense mechanism against hyperproliferation and malignancy, which can be induced by e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Beside the extensively studied role of the above mentioned caspase 8 polymorphisms in cancer susceptibility, recent approaches also started to investigate, whether these polymorphisms also influence the outcome of cancer in patients with already existing disease. In this context, recent pilot investigations reported a negative prognostic impact for the CASP8 -652 Del allele or the CASP8 302His allele for patients with colon cancer or neuroblastoma, respectively [ 18 , 19 ]. However, although breast cancer was primarily adressed by recent CASP8 -652 6N Del and CASP8 Asp302His susceptibility studies, surprisingly, prognostic relevance of these caspase 8 polymorphisms has not been investigated in breast cancer so far.…”

Section: Introductionmentioning

confidence: 99%

Prognostic relevance of caspase 8 -652 6N InsDel and Asp302His polymorphisms for breast cancer

et al. 2016

View full text Add to dashboard Cite

BackgroundThe minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study.MethodsGenotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR.ResultsWe 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). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p = 0.0018, p = 0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p = 0.007, p = 0.037, respectively). Prognostic relevance of both polymorphisms were confirmed to be independent from each other and combined analysis of diplotypes revealed an additive influence upon OS (p = 0.0002).ConclusionThis is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2662-x) contains supplementary material, which is available to authorized users.

show abstract

“…18,37 CASP8 polymorphisms were related to many cancers, including lung cancer and neuroblastoma. [38][39][40] Son et al found that CASP8 IVS12-19 GG genotype was significantly increased for the risk of small cell carcinoma (SmCC), rather than IVS12-19 AA and IVS12-19 GA genotypes. 38 However, this is the first time that rs3769821 and rs1045494 of CASP8 was reported to be associated with lung adenocarcinoma OS in our study, and the patients with AA genotype of rs3769821 had 6.7 months longer OS than patients with GG or AG genotypes (p D 0.007).…”

Section: Immortality Of Injured Cells and Induction Of Various Cancersmentioning

confidence: 99%

Caspase 8polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy

Liu

Ding

et al. 2017

Cancer Biology & Therapy

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer deaths in China, and about 60% of the cases are diagnosed with histological adenocarcinoma. The caspase 8 (CASP8) gene is a critical initiator of the extrinsic apoptosis pathway. To explore the relationship between tagSNPs or haplotypes of CASP8 and the efficacy of platinum-based chemotherapy in advanced lung adenocarcinoma patients of China, we recruited 555 advanced adenocarcinoma patients. We extracted the genomic DNA from patients' peripheral blood samples and sequenced tagSNPs of CASP8. We calculated the individual haplotype of CASP8 frequencies using the PHASE 2.0 program. The association between CASP8 tagSNPs and overall survival (OS) was calculated by univariate and multivariate Cox regression analysis. A univariate logistic regression analysis was done to analyze the CASP8 tagSNPs and the toxicity of platinum-based chemotherapy. The same statistical methods were used for exploring haplotypes of CASP8. Rs3769821 and rs1045494 of CASP8 were independent prognosis factors for overall survival (OS) using multivariate Cox's regression models. For the haplotype of the 7 tagSNPs, haplotype AGGAAAGA was correlated with the efficacy of platinum-based chemotherapy. The polymorphisms of CASP8, rs7608692, and haplotype AGAACAG correlated with neutropenia toxicity. The haplotype GGGGAAA was associated with thrombocytopenia toxicity. We conclude that the polymorphisms of CASP8 contribute to the prognosis of advanced lung adenocarcinoma and influence the quality of life and survival.

show abstract

CASP8 SNP D302H (rs1045485) Is Associated with Worse Survival in MYCN-Amplified Neuroblastoma Patients

Cited by 19 publications

References 35 publications

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan

Association of Caspase-8 Genotypes With Oral Cancer Risk in Taiwan

Prognostic relevance of caspase 8 -652 6N InsDel and Asp302His polymorphisms for breast cancer

Caspase 8polymorphisms contribute to the prognosis of advanced lung adenocarcinoma patients after platinum-based chemotherapy

Contact Info

Product

Resources

About