The Significance of Exo1 K589E Polymorphism on Cancer Susceptibility: Evidence Based on a Meta-Analysis

Duan, Fujiao; Song, Chunhua; Dai, Liping; Cui, Shuaiying; Zhang, Xiaoqin; Zhao, Xia

doi:10.1371/journal.pone.0096764

Cited by 10 publications

(12 citation statements)

References 23 publications

(20 reference statements)

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“…However, we found that the data reported by Bayram 41 from the studies by Wang et al 23 and Ibarrola-Villava et al 26 were not the same as the original data. Another recent meta-analysis by Duan et al 42 concluded that the Glu589Lys polymorphism was significantly associated with increased cancer risk in all genetic models, which differed from our own results. This may be explained by the relatively small sample size.…”

Section: Discussioncontrasting

confidence: 99%

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Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

Chen¹,

Zheng²,

Zhong³

et al. 2016

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To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result.

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Section: Discussioncontrasting

confidence: 99%

“…Interestingly, Bayram 41 and Duan et al 42 have conducted meta-analyses to identify whether there was any evidence of a relationship between the Exo1 Glu589Lys polymorphism and cancer susceptibility. Their conclusions could be considered to be inconsistent, which may be partially attributable to the relatively small sample size.…”

Section: Discussionmentioning

confidence: 99%

Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

Chen¹,

Zheng²,

Zhong³

et al. 2016

OTT

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“…A widely assessed non-synonymous single nucleotide polymorphism (SNP) at codon 589 (rs1047840KE) is closely associated with increased susceptibility to lung cancer [17][18][19], gastric cancer [20], cervical cancer [21], breast cancer [22], oral cancer [23], colorectal cancer [24], glioma [25] and HCC [26]. Such SNP could be used as a biomarker of carcinogenesis [27]. Besides, partly due to the heterogeneity of different cancer types, it remains an open question whether other moderate genetic polymorphisms induce or inverse cancer susceptibility.…”

Section: Introductionmentioning

confidence: 99%

EXO1 overexpression is associated with poor prognosis of hepatocellular carcinoma patients

et al. 2018

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The roles of exonuclease 1 (EXO1) in hepatocellular carcinoma (HCC) tumorigenesis and progression remain unclear. This study aimed to assess the prognostic value and therapeutic potential of EXO1 in HCC. Exo1 gene copy numbers were obtained from three Oncomine microarray datasets (n = 447). EXO1 mRNA expression was validated by semi-quantitative PCR and QuantiGene® 2.0 assays. Cell growth curve and colony formation were performed to asses the cell proliferation. Clonogenic assay, flow cytometry, and immunofluorescence were adopted to acess the effects of EXO1 knockdown and radiation on cell survival, cell cycle distribution and DNA repair. Western blots were performed to reveal the related mechanism. A significant copy number variation (CNV) of the Exo1 gene was found in HCC specimens in three separate sets of published microarray data. In the 143 cases treated by our team, EXO1 expression levels were elevated (86.71%, 124/143). In addition, EXO1 overexpression was correlated with larger tumor size (P = 0.002), increased lymph node metastasis (P=0.033) and lower Edmondson grade (P = 0.018). High EXO1 expression unfavorably affected overall survival (OS) (P = 0.009). Both univariate and multivariate Cox regression analyses identified EXO1 as an independent predictor of OS (univariate, P = 0.012; multivariate, P = 0.039). Silencing of EXO1 in vitro reduced cell proliferation. EXO1 knockdown further suppressed clonogenic cell survival, abrogated radiation-induced G2/M phase arrest, and enhanced γ-H2AX foci after exposure to irradiation. The accumulation of ataxiatelangiectasia mutated (ATM) might partially regulate the EXO1 related radiosensitivity. In summary, EXO1 could be a promising prognostic marker, with a potential therapeutic value in HCC.

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“…This suggested the effect to be ethnicity dependent. 43 We also estimated the allele frequency of both CDH1 (-160C/A) and Exo1 (K589E) SNPs for both prostate cancer cases and controls. Our results demonstrated that the variant A allele in CDH1 (-160C/A) and Exo1 (K589E) genes was significantly associated with increased risk of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms in CDH1 and Exo1 genes elevate the prostate cancer risk in Bangladeshi population

et al. 2019

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The polymorphisms of invasion suppressor gene CDH1 and DNA mismatch repair gene Exo1 have been reported to play critical role in the development, tumorigenesis, and progression of several kinds of cancers including prostate cancer. This study was designed to analyze the contribution of single-nucleotide polymorphisms of the CDH1 (-160C/A) and Exo1 (K589E) to prostate cancer susceptibility in Bangladeshi population. The study included 100 prostate cancer cases and age-matched 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to determine the genetic polymorphisms. A significant association was found between CDH1 -160C/A (rs16260) and Exo1 (rs1047840, K589E) polymorphisms and prostate cancer risk. In case of CDH1 -160C/A polymorphism, the frequencies of the three genotypes C/C,C/A, and A/A were 45%, 48%, and 7% in cases and 63%, 32%, and 5% in controls, respectively. The heterozygote C/A genotype and combined C/A+A/A genotypes showed 2.10-fold (odds ratio = 2.1000, 95% confidence interval = 1.2956-4.0905, p = 0.013) and 2.08-fold (odds ratio = 2.0811, 95% confidence interval = 1.1820-3.6641, p = 0.011) increased risk of prostate cancer, respectively, when compared with homozygous C/C genotypes. The variant A allele also was associated with increased risk of prostate cancer (odds ratio = 1.6901, 95% confidence interval = 1.0740-2.6597, p = 0.0233). In case of Exo1 (K589E) polymorphism, G/A heterozygote, A/A homozygote, and combined G/A+A/A genotypes were found to be associated with 2.30-, 4.85-, and 3.04-fold higher risk of prostate cancer, respectively (odds ratio = 2.3021, 95% confidence interval = 2.956-4.0905, p = 0.0031; odds ratio = 4.8462, 95% confidence interval = 1.0198-23.0284, p = 0.0291; OR = 3.0362, 95% confidence interval = 1.7054-5.4053, p = 0.0001, respectively). The ''A'' allele showed significant association with increased susceptibility (2.29-fold) to prostate cancer (odds ratio = 2.2955, 95% confidence interval = 1.4529-3.6270, p = 0.0004). Our results suggest that CDH1 -160C/A and Exo1 K589E polymorphisms are associated with increased susceptibility to prostate cancer in Bangladeshi population.

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The Significance of Exo1 K589E Polymorphism on Cancer Susceptibility: Evidence Based on a Meta-Analysis

Cited by 10 publications

References 23 publications

Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

EXO1 overexpression is associated with poor prognosis of hepatocellular carcinoma patients

Genetic polymorphisms in CDH1 and Exo1 genes elevate the prostate cancer risk in Bangladeshi population

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