Associations of mRNA expression of DNA repair genes and genetic polymorphisms with cancer risk: a bioinformatics analysis and meta-analysis

Wu, Huizhe; Li, Shanqiong; Hu, Xiaoyun; Qin, Wenyan; Wang, Yilin; Wu, Zhuona; Wang, Xiufang; Lu, Senxu; Xu, Dong-ping; Li, Yalun; Guan, Sheng; Zhao, Haishan; Yao, Weifan; Liu, Mingyan

doi:10.7150/jca.30975

Cited by 18 publications

(15 citation statements)

References 75 publications

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“…A recent meta-analysis demonstrated that ERCC2 rs13181 GG genotype has a positive prognostic value in predicting the overall survival of HCC patients [56]. On the other hand, rs238406 TT genotype was associated with an increased overall cancer risk [60]. In our study, both SNPs were associated with liver cirrhosis development.…”

Section: Discussionsupporting

confidence: 57%

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

Rybicka

Woziwodzka

Sznarkowska

et al. 2020

Cancers

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Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course. DNA repair enzymes can affect dynamics of liver damage and are involved in HBV covalently closed circular DNA (cccDNA) formation, an essential step for viral replication. This study aimed to evaluate the possible role of genes representing key DNA-repair pathways in HBV-induced liver damage. MALDI-TOF MS genotyping platform was applied to evaluate variations within XRCC1, XRCC4, ERCC2, ERCC5, RAD52, Mre11, and NBN genes. Apart from older age (p < 0.001), female sex (p = 0.021), portal hypertension (p < 0.001), thrombocytopenia (p < 0.001), high HBV DNA (p = 0.001), and high aspartate aminotransferase (AST) (p < 0.001), we found that G allele at rs238406 (ERCC2, p = 0.025), T allele at rs25487 (XRCC1, p = 0.012), rs13181 GG genotype (ERCC2, p = 0.034), and C allele at rs2735383 (NBN, p = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (p = 0.005) and rs238406 TT (p = 0.027) were independently associated with lower risk of LC. This study provides evidence for the impact of functional and potentially functional variations in key DNA-repair genes XRCC1 and ERCC2 in HBV-induced liver damage in a Caucasian population.

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Section: Discussionsupporting

confidence: 57%

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

Rybicka

Woziwodzka

Sznarkowska

et al. 2020

Cancers

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“…Clinical studies have found that different individuals with the same clinical characteristics show great heterogeneity in clinical manifestations, treatment sensitivity, disease recurrence, and survival outcomes. We have previously reported on individual differences in genetic susceptibility, (31)(32)(33). However, a large number of research results are inconsistent, and there is no consensus on whether differences in DNA repair gene expression can be used as prognostic indicators.…”

Section: Discussionmentioning

confidence: 99%

DNA repair genes are associated with tumor tissue differentiation and immune environment in lung adenocarcinoma: a bioinformatics analysis based on big data

Zhou

Zhang

et al. 2021

J Thorac Dis

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Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. DNA repair genes (DRGs) is important in lung cancer. The relationship between the immune environment and the expression levels of DRGs in LUAD remains unclear. The purpose of this study is to assess the relationship between DRGs and the immune environment and clinical characteristics of LUAD. Methods: Data of 169 LUAD cases were obtained from cbioportal. The RNA-seq data came from the The Cancer Genome Atlas (TCGA) database. We collected DRGs from the Reactom database (KW0037, Reactom.org). The 302 genes expressed in each sample were analyzed by hierarchical clustering and grouped using the Gene Cluster 3.0 program. The Java Treeview program was used to generate heat maps of cluster indications and tumor staging patterns. GraphPad Prism 8 was used to draw survival curves and compare overall survival (OS). For single genes, an OS difference analysis between low and high expression populations was performed in GraphPad Prism 8. Results: Matrix clustering showed no difference in the prognosis of the two clusters. The comparison of subgroups showed that Subcluster 1 (SC1) had the best prognosis, and Subcluster 2 (SC2) had the worst. There was a significant difference in tumor grades between Cluster 1 and Cluster 2 (P=0.01). There were significant differences in smoking status, histological grade and adenocarcinoma subtype among subgroups.In Subcluster 3 (SC3), the proportion of poorly differentiated cases was highest. Immunological index analysis showed that there were significant differences between Cluster 1 and Cluster 2 in interferon, macrophages, monocytes, neutrophils, natural killer (NK) cells, and T cells. Tumor purity, interferon, macrophages, monocytes, neutrophils, NK cells, T cells, translation, and proliferation all showed significant differences between subgroups. In SC2, the proliferation index increased (0.082 vs. 0.070); the protein translation index decreased (0.134 vs. 0.137); and the interferon level increased (0.099 vs. 0.097). In SC3, the proliferation index decreased (0.076 vs. 0.071); the protein translation index decreased (0.140 vs. 0.136); and the level of neutrophils increased (0.083 vs. 0.086). Conclusions: The differences of DRGs in LUAD are related to tissue differentiation and immune indicators but not to prognosis.

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“…Recently, the most comprehensive meta-analysis for rs10817938 and rs2808668 and cancer risk (33 types of cancer were examined) showed that harbouring rs10817938 homozygous CC genotype, C allele, and CC/CT genotype in a dominant setting associates with an increased overall cancer risk, with a specific association with digestive system cancers. In contrast, there was no association with overall cancer risk for rs2808668, albeit subgroup analysis revealed a decreased risk in the majority of cancers examined, with the exception of digestive system cancer [156]. In addition, this SNP interacts with environmental factors, such as alcohol consumption in gastric cancer (GC), and clinical-pathological characteristics, such as tumour size, metastatic status at onset, and mitotic index in gastrointestinal stromal cancer [157,158].…”

Section: Xpa Polymorphisms and Cancer Incidence And Treatment Outcomementioning

confidence: 99%

“…Changes in the expression level of XPA are assumed to significantly contribute to cancer risk, disease prognosis and treatment outcome. To identify the potential role of XPA mRNA expression in different cancer types, Wu et al [156] used two approaches: (i) comparison of the XPA mRNA expression in 13 types of cancers from the RNA sequencing dataset platform GENT (Gene Expression Database of Normal and Tumor Tissues, http://medical-genome.kribb.re.kr/GENT/) and (ii) freely available information on XPA expression in 19 types TCGA (The Cancer Genome Atlas) datasets and their normal controls from ONCOMINE, a cancer microarray database and web-based data-mining platform (https://www.oncomine.org/). These approaches revealed decreased expression of XPA in a range of tumours, including bladder, kidney, liver, lung (also seen in [195]), prostate, and stomach cancers.…”

Section: Xpa Expression As a Cancer Risk Factor And Its Prognostic And Predictive Valuementioning

confidence: 99%

XPA: DNA Repair Protein of Significant Clinical Importance

Pulzová¹,

Ward

Chovanec³

2020

IJMS

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The nucleotide excision repair (NER) pathway is activated in response to a broad spectrum of DNA lesions, including bulky lesions induced by platinum-based chemotherapeutic agents. Expression levels of NER factors and resistance to chemotherapy has been examined with some suggestion that NER plays a role in tumour resistance; however, there is a great degree of variability in these studies. Nevertheless, recent clinical studies have suggested Xeroderma Pigmentosum group A (XPA) protein, a key regulator of the NER pathway that is essential for the repair of DNA damage induced by platinum-based chemotherapeutics, as a potential prognostic and predictive biomarker for response to treatment. XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site, mediated by protein–protein interactions. In this review, we focus on the interacting partners and mechanisms of regulation of the XPA protein. We summarize clinical oncology data related to this DNA repair factor, particularly its relationship with treatment outcome, and examine the potential of XPA as a target for small molecule inhibitors.

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Associations of mRNA expression of DNA repair genes and genetic polymorphisms with cancer risk: a bioinformatics analysis and meta-analysis

Cited by 18 publications

References 75 publications

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

DNA repair genes are associated with tumor tissue differentiation and immune environment in lung adenocarcinoma: a bioinformatics analysis based on big data

XPA: DNA Repair Protein of Significant Clinical Importance

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