The Exonuclease 1 Glu589Lys Gene Polymorphism and Cancer Susceptibility: Evidence Based on a Meta-analysis

Bayram, Süleyman

doi:10.7314/apjcp.2014.15.6.2571

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…Their conclusions could be considered to be inconsistent, which may be partially attributable to the relatively small sample size. The meta-analysis by Bayram 41 showed that the Glu589Lys polymorphism was not associated with overall cancer susceptibility, which contrasted with our own results. 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.…”

Section: Discussioncontrasting

confidence: 99%

“…The meta-analysis by Bayram 41 showed that the Glu589Lys polymorphism was not associated with overall cancer susceptibility, which contrasted with our own results. 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.…”

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%

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

Chen¹,

Zheng²,

Zhong³

et al. 2016

OTT

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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%

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

OTT

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“…Exo1 knockout mice exhibit reduced survival, increased susceptibility to developing lymphomas (14), and sterility in both males and females (14). Defects in hExo1 are implicated in human cancers (15).…”

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confidence: 99%

Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I

Shi

Hellinga

Beese

2017

Proc. Natl. Acad. Sci. U.S.A.

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Human exonuclease 1 (hExo1) is a member of the RAD2/XPG structure-specific 5'-nuclease superfamily. Its dominant, processive 5'-3' exonuclease and secondary 5'-flap endonuclease activities participate in various DNA repair, recombination, and replication processes. A single active site processes both recessed ends and 5'-flap substrates. By initiating enzyme reactions in crystals, we have trapped hExo1 reaction intermediates that reveal structures of these substrates before and after their exo- and endonucleolytic cleavage, as well as structures of uncleaved, unthreaded, and partially threaded 5' flaps. Their distinctive 5' ends are accommodated by a small, mobile arch in the active site that binds recessed ends at its base and threads 5' flaps through a narrow aperture within its interior. A sequence of successive, interlocking conformational changes guides the two substrate types into a shared reaction mechanism that catalyzes their cleavage by an elaborated variant of the two-metal, in-line hydrolysis mechanism. Coupling of substrate-dependent arch motions to transition-state stabilization suppresses inappropriate or premature cleavage, enhancing processing fidelity. The striking reduction in flap conformational entropy is catalyzed, in part, by arch motions and transient binding interactions between the flap and unprocessed DNA strand. At the end of the observed reaction sequence, hExo1 resets without relinquishing DNA binding, suggesting a structural basis for its processivity.

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Influence of a single-nucleotide polymorphism of the DNA mismatch repair-related gene exonuclease-1 (rs9350) with prostate cancer risk among Chinese people

Zhang

et al. 2015

Tumor Biol.

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In this study, we aimed to identify the influence of exonuclease 1 (EXO1) single-nucleotide polymorphism rs9350, which is involved in DNA mismatch repair, on prostate cancer risk in Chinese people. In our hospital-based case-control study, 214 prostate cancer patients and 253 cancer-free control subjects were enrolled from three hospitals in China. Genotyping for rs9350 was performed by the SNaPshot(®) method using peripheral blood samples. Consequently, a significantly higher prostate cancer risk was observed in patients with the CC genotype [odds ratio (OR) = 1.678, 95 % confidence interval (CI) = 1.130-2.494, P = 0.010] than in those with the CT genotype. Further, the CT/TT genotypes were significantly associated with increased prostate cancer risk (adjusted OR = 1.714, 95 % CI = 1.176-2.500, P = 0.005), and the C allele had a statistically significant compared with T allele (P = 0.009) of EXO1 (rs9350). Through stratified analysis, significant associations were revealed for the CT/TT genotype in the subgroup with diagnosis age >72 (adjusted OR = 1.776, 95 % CI = 1.051-3.002, P = 0.032) and in patients with localized disease subgroup (adjusted OR = 1.798, 95 % CI = 1.070-3.022, P = 0.027). In addition, we observed that patients with prostate-specific antigen (PSA) levels of ≤10 ng/mL were more likely to have the CT/TT genotypes than those with PSA levels of >10 ng/mL (P = 0.006). For the first time, we present evidence that the inherited EXO1 polymorphism rs9350 may have a substantial influence on prostate cancer risk in Chinese people. We believe that the rs9350 could be a useful biomarker for assessing predisposition for and early diagnosis of prostate cancer.

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The Exonuclease 1 Glu589Lys Gene Polymorphism and Cancer Susceptibility: Evidence Based on a Meta-analysis

Cited by 3 publications

References 17 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

Interplay of catalysis, fidelity, threading, and processivity in the exo- and endonucleolytic reactions of human exonuclease I

Influence of a single-nucleotide polymorphism of the DNA mismatch repair-related gene exonuclease-1 (rs9350) with prostate cancer risk among Chinese people

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