Flap endonuclease‐1 rs174538 G&gt;A polymorphisms are associated with the risk of esophageal cancer in a Chinese population

Sang, Yonghua; Lin, Bo; Gu, Heng; Yang, Wengtao; Chen, Yongbing

doi:10.1111/1759-7714.12422

Cited by 9 publications

(13 citation statements)

References 28 publications

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“…They were both upregulated in EC. Despite being implicated in various cancer types, their role in EC has not been studied before [ 64 , 65 , 66 , 67 , 68 ]. Our methodology is validated by some TTAGPs relevant to EC that had previously been confirmed by other authors, for example; FOXA1 was also a highly upregulated DEG, which is known to regulate oestrogen receptor binding in breast cancer [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

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Hill

et al. 2020

MPs

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Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including NOP56, WFS1, ANAPC4 and TUBB4A. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.

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Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

Button

Hill

et al. 2020

MPs

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“…However, due to the complex mechanism of TNBC metastasis, some aspects remain unknown. FEN1 has been identified as a potential biomarker from previous studies, which found that overexpression of FEN1 could disrupt the cell cycle and promote cell proliferation in numerous types of cancer, including breast cancer ( 13 , 24 , 35 , 36 ). Furthermore, FEN1 overexpression was also associated with resistance to chemotherapy ( 18 , 22 ), and targeted therapy ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Biological and clinical significance of flap endonuclease‑1 in triple‑negative breast cancer: Support of metastasis and a poor prognosis

Song

Zhang

et al. 2020

Oncol Rep

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Flap endonuclease-1 (FEN1), a structure-specific nuclease participating in DNA replication and repair processes, has been confirmed to promote the proliferation and drug resistance of tumor cells. However, the biological functions of FEN1 in cancer cell migration and invasion have not been defined. In the present study, using online database analysis and immunohistochemistry of the specimens, it was found that FEN1 expression was associated with a highly invasive triple-negative breast cancer (TNBC) subtype in both breast cancer samples from the Oncomine database and from patients recruited into the study. Furthermore, FEN1 was an important biomarker of lymph node metastasis and poor prognosis in patients with TNBC. FEN1 promoted migration of TNBC cell lines and FEN1 knockdown reduced the number of spontaneous lung metastasis in vivo . Ingenuity Pathway Analysis of FEN1-related transcripts in 198 patients with TNBC demonstrated that the polo-like kinase family may be the downstream target of FEN1. PLK4 was further identified as a critical target of FEN1 mediating TNBC cell migration, by regulating actin cytoskeleton rearrangement. The results of the present study validate FEN1 as a therapeutic target in patients with TNBC and revealed a new role for FEN1 in regulating TNBC invasion and metastasis.

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“…Association study with 1840 lung cancer patients and 1958 controls further revealed that these two FEN1 SNPs conferred genetic susceptibility to lung cancer [ 49 ]. Moreover, some evidence was further observed to consolidate the contribution of the rs174538 and rs4246215 to the risk of different types of cancer [ 25 , 36 , 37 , 39 ]. Especially, these two SNPs were shown to decrease breast cancer risk in Chinese [ 25 ]and Iran [ 37 ] populations.…”

Section: Discussionmentioning

confidence: 99%

Base Excision Repair Gene Polymorphisms and Wilms Tumor Susceptibility

Zhu

Jia

et al. 2018

EBioMedicine

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Base excision repair (BER) is the main mechanism to repair endogenous DNA lesions caused by reactive oxygen species. BER deficiency is linked with cancer susceptibility and premature aging. Single nucleotide polymorphisms (SNPs) within BER genes have been implicated in various human malignancies. Nevertheless, a comprehensive investigation of their association with Wilms tumor susceptibility is lacking. In this study, 145 cases and 531 sex and age-matched healthy controls were recruited. We systematically genotyped 18 potentially functional SNPs in six core BER pathway genes, using a candidate SNP approach. Logistic regression was employed to evaluate odds ratio (OR) and 95% confidence interval (CI) adjusted for age and gender. Several SNPs showed protective effects against Wilms tumor. Significant associations with Wilms tumor susceptibility were shown for hOGG1 rs1052133 (dominant: adjusted OR = 0.66, 95% CI = 0.45–0.96, P = .030), FEN1 rs174538 (dominant: adjusted OR = 0.66, 95% CI = 0.45–0.95, P = .027; recessive: adjusted OR = 0.54, 95% CI = 0.32–0.93 P = .027), and FEN1 rs4246215 (dominant: adjusted OR = 0.55, 95% CI = 0.38–0.80, P = .002) polymorphisms. Stratified analysis was performed by age, gender, and clinical stage. Moreover, there was evidence of functional implication of these significant SNPs suggested by online expression quantitative trait locus (eQTL) analysis. Our findings indicate that common SNPs in BER genes modify susceptibility to Wilms tumor.

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Flap endonuclease‐1 rs174538 G>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population

Cited by 9 publications

References 28 publications

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Biological and clinical significance of flap endonuclease‑1 in triple‑negative breast cancer: Support of metastasis and a poor prognosis

Base Excision Repair Gene Polymorphisms and Wilms Tumor Susceptibility

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