Associations between Nine Polymorphisms in EXO1 and Cancer Susceptibility: A Systematic Review and Meta-Analysis of 39 Case-control Studies

Zhang, Meng; Zhao, Duran; Yan, Cairong; Zhang, Li; Liang, Chaozhao

doi:10.1038/srep29270

Cited by 15 publications

(15 citation statements)

References 23 publications

(40 reference statements)

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“…It is well in accordance with the theory of the driver and passenger somatic mutations in human cancer genome 26. Rs851797, located at 3′-UTR of EXO1 gene, was found to be associated with risk of several human cancers 11. In silico analysis by using the RNAfold online tool showed that rs851797 could alter the local secondary structure of the EXO1 mRNA based on the MFE value, thus contribute to tumor progression and prognosis.…”

Section: Discussionsupporting

confidence: 74%

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Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer

Shi¹,

Jiang²,

Wang³

et al. 2017

OTT

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BackgroundExonuclease 1 (EXO1), one of DNA mismatch repair pathway genes, functions in maintaining genomic stability and affects tumor progression. We hypothesized that genetic variations in EXO1 may predict clinical outcomes in epithelial ovarian cancer (EOC).MethodsIn this cohort study with 1,030 consecutive EOC patients, we genotyped four potentially functional polymorphisms in EXO1 by the Taqman assay and evaluated their associations with patients’ survival.ResultsUsing multivariate Cox proportional hazards regression models, we found that rs851797AG/GG genotypes were significantly associated with recurrence and cancer death (HR =1.30 and 1.38, 95% CI =1.11–1.52 and 1.02–1.88, respectively). Kaplan–Meier survival estimates showed that patients who carried rs851797AG/GG genotypes had poorer progression-free survival and poorer overall survival, compared with rs851797AA genotype carriers (log-rank test, P=0.002 and 0.025, respectively). Moreover, patients with older age at menophania, advanced stage tumor, or being received incomplete cytoreduction were more likely to be recurrent and dead.ConclusionEXO1 rs851797 polymorphism can predict the clinical outcomes in EOC patients. In addition, age at menophania, FIGO stage, and complete cytoreduction might be independently prognostic factors of ovarian cancer. Large studies with functional experiments are warranted to validate these findings.

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Section: Discussionsupporting

confidence: 74%

“…Meta-analysis showed that EXO1 rs851797 was conferred an increased overall susceptibility to cancer in an allelic model 11. Recently, a pooled genome-wide association study reported that the EXO1 polymorphism region (1q43) was associated with the risk of EOC 17.…”

Section: Discussionmentioning

confidence: 99%

Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer

Shi¹,

Jiang²,

Wang³

et al. 2017

OTT

View full text Add to dashboard Cite

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“…EXO1, a DNA mismatch repair gene, its polymorphisms have been reported to play a critical role in the development of many tumors (Shi et al, 2017;Zhang et al, 2016). Also, due to its role in DNA replication repair and homology-directed repair, the relationships of EXO1 and BRCA1/2 mutations and its underlying mechanism have become an important focus to be studied (Lemacon et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses

Zhou

Liu

et al. 2020

PeerJ

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Background BRCA1 and BRCA2 genes are currently proven to be closely related to high lifetime risks of breast cancer. To date, the closely related genes to BRCA1/2 mutations in breast cancer remains to be fully elucidated. This study aims to identify the gene expression profiles and interaction networks influenced by BRCA1/2 mutations, so as to reflect underlying disease mechanisms and provide new biomarkers for breast cancer diagnosis or prognosis. Methods Gene expression profiles from The Cancer Genome Atlas (TCGA) database were downloaded and combined with cBioPortal website to identify exact breast cancer patients with BRCA1/2 mutations. Gene set enrichment analysis (GSEA) was used to analyze some enriched pathways and biological processes associated BRCA mutations. For BRCA1/2-mutant breast cancer, wild-type breast cancer and corresponding normal tissues, three independent differentially expressed genes (DEGs) analysis were performed to validate potential hub genes with each other. Protein–protein interaction (PPI) networks, survival analysis and diagnostic value assessment helped identify key genes associated with BRCA1/2 mutations. Results The regulation process of cell cycle was significantly enriched in mutant group compared with wild-type group. A total of 294 genes were identified after analysis of DEGs between mutant patients and wild-type patients. Interestingly, by the other two comparisons, we identified 43 overlapping genes that not only significantly expressed in wild-type breast cancer patients relative to normal tissues, but more significantly expressed in BRCA1/2-mutant breast patients. Based on the STRING database and cytoscape software, we constructed a PPI network using 294 DEGs. Through topological analysis scores of the PPI network and 43 overlapping genes, we sought to select some genes, thereby using survival analysis and diagnostic value assessment to identify key genes pertaining to BRCA1/2-mutant breast cancer. CCNE1, NPBWR1, A2ML1, EXO1 and TTK displayed good prognostic/diagnostic value for breast cancer and BRCA1/2-mutant breast cancer. Conclusion Our research provides comprehensive and new insights for the identification of biomarkers connected with BRCA mutations, availing diagnosis and treatment of breast cancer and BRCA1/2-mutant breast cancer patients.

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“…Only a variant in gene EXO1 (NM_130398.3:c.*84T>G) was predicted as a likely true candidate for affecting miRNA binding, for miR-370-3p and miR-93-3p (see S3 Table ). Several studies have shown the importance of EXO1 in replication, DNA repair pathways, cell cycle checkpoints and its association to cancer [ 76 ], and GWAS studies have identified specific mutations in EXO1 gene as risk alleles for different types of cancer [ 77 , 78 ]. SNPs in miRNA binding sites have been associated with CRC [ 79 ].…”

Section: Resultsmentioning

confidence: 99%

Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer

et al. 2020

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Germline variants inactivating the mismatch repair (MMR) genes MLH1 , MSH2 , MSH6 and PMS2 cause Lynch syndrome that implies an increased cancer risk, where colon and endometrial cancer are the most frequent. Identification of these pathogenic variants is important to identify endometrial cancer patients with inherited increased risk of new cancers, in order to offer them lifesaving surveillance. However, several other genes are also part of the MMR pathway. It is therefore relevant to search for variants in additional genes that may be associated with cancer risk by including all known genes involved in the MMR pathway. Next-generation sequencing was used to screen 22 genes involved in the MMR pathway in constitutional DNA extracted from full blood from 199 unselected endometrial cancer patients. Bioinformatic pipelines were developed for identification and functional annotation of variants, using several different software tools and custom programs. This facilitated identification of 22 exonic, 4 UTR and 9 intronic variants that could be classified according to pathogenicity. This study has identified several germline variants in genes of the MMR pathway that potentially may be associated with an increased risk for cancer, in particular endometrial cancer, and therefore are relevant for further investigation. We have also developed bioinformatics strategies to analyse targeted sequencing data, including low quality data and genomic regions outside of the protein coding exons of the relevant genes.

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Associations between Nine Polymorphisms in EXO1 and Cancer Susceptibility: A Systematic Review and Meta-Analysis of 39 Case-control Studies

Cited by 15 publications

References 23 publications

Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer

Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer

Differentially expressed genes and key molecules of BRCA1/2-mutant breast cancer: evidence from bioinformatics analyses

Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer

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