Dataset Information

Significant Contribution of DNA Repair Human 8-Oxoguanine DNA N-Glycosylase 1 Genotypes to Renal Cell Carcinoma.

ABSTRACT: Introduction:DNA repair systems play essential roles in genomic stability and carcinogenesis. Therefore, genotypes at DNA repair loci may contribute to the determination of personal susceptibility to cancers. The contribution of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) genotypes to renal cell carcinoma (RCC) is largely unknown. This study aimed to evaluate the contributions of hOGG1 rs1052133 genotypes to the RCC risk. Methods:We evaluated the contribution of hOGG1 rs1052133 (G/C) genotypes among 118 cases and 590 controls and analyzed the interactions of hOGG1 genotypes with smoking, alcohol drinking, hypertension, and diabetes status. Results:The hOGG1 rs1052133 CC genotype was significantly associated with a decreased RCC risk compared with that of the GG genotype (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.09-0.72, p = 0.0049). The frequency of the rs1052133 C allele was significantly low in the RCC group (22.5% vs 31.2%; OR = 0.64; 95% CI = 0.46-0.89, p = 0.0074). Stratifying the analysis according to smoking, alcohol drinking, and diabetes status revealed no difference in the rs1052133 genotype distribution among these subgroups. A significant differential distribution of rs1052133 genotypes was observed among subjects with hypertension. Conclusion:The CC genotype of rs1052133 may play a role in determining RCC susceptibility among Taiwanese people and may serve as a biomarker of RCC, particularly in patients with hypertension.

SUBMITTER: Chang WS

PROVIDER: S-EPMC7039087 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Significant Contribution of DNA Repair <i>Human 8-Oxoguanine DNA N-Glycosylase 1</i> Genotypes to Renal Cell Carcinoma.

Chang Wen-Shin WS Shen Te-Chun TC Liao Jiuan-Miaw JM Tsai Yueh-Ting YT Hsia Te-Chun TC Wu Hsi-Chin HC Tsai Chia-Wen CW Bau Da-Tian DT

OncoTargets and therapy 20200220

<h4>Introduction</h4>DNA repair systems play essential roles in genomic stability and carcinogenesis. Therefore, genotypes at DNA repair loci may contribute to the determination of personal susceptibility to cancers. The contribution of <i>human 8-oxoguanine DNA N-glycosylase 1</i> (<i>hOGG1</i>) genotypes to renal cell carcinoma (RCC) is largely unknown. This study aimed to evaluate the contributions of <i>hOGG1</i> rs1052133 genotypes to the RCC risk.<h4>Methods</h4>We evaluated the contributi ...[more]

PMID: 32110055

Similar Datasets

Project description:Purpose: The aim of this study is to test whether global gene expression induced by multiple challenges with OGG1-BER product 8-oxoG in mouse airways is linked to airway remodeling. Methods: RNAs extracted from individual mouse lungs (experimental group: n=5) were pooled and a total 1 ?g RNA was used for Next-Generation Sequencing (NGS) analyses on an Illumina HiSeq 1000 sequencing system. Sequence analyses were performed in duplicate. First- and second-strand synthesis, adapter ligation and amplification of the library were performed using the Illumina TruSeq Sample Preparation Kit as recommended by the manufacturer (Illumina). Library quailty was evaluated by using an Agilent DNA-1000 chip on an Agilent 2100 Bioanalyzer. Library DNA templates were quantitated by qPCR using known reference standards. Cluster formation of the library of DNA templates was performed using the TruSeq PE Cluster Kit v3 (Illumina) and the Illumina cBot workstation. Paired-end, 50-base sequencing was performed with a TruSeq SBS kit v3 (Illumina) on the Illumina HiSeq 1000 by protocols defined by the manufacturer. Base call conversion to sequence reads was performed using CASAVA-1.8.2. Sequence data were analyzed with the Bowtie2, Tophat2 and GFOLD programs. Processed data are presented as reads per kilobase transcript per million (RPKM), normalized to the experimental control (RNA from saline challenged lungs) and reported as fold change (test/control). Results: We mapped an average of 31.41 million sequence reads per sample and identified 23,337 transcripts in total RNA extracted from lungs of Balb/cJ mice as described in Methods. Approximately 14% of the transcripts showed differential expression between the saline-challenged control and 8-oxoguanine-challeged mouse lungs, with a fold change ?3.0. We validated the expression changes of 18 selected EMT-related genes of interest for our studies by qRT-PCR. Hierarchical clustering followed by Protein ANalysis THrough Evolutionary Relationships database (PANTHER) analysis of differentially expressed genes was done using GENE-E online software from Broad Institute (http://www.broadinstitute.org/cancer/software/GENE-E/). Results from PANTHER analysis of upregulated transcripts (fold change ?3.0) showed overrepresentation of various biological functions (GO terms) including developmental process (GO:0032502, P=4.58E-33), system development (GO:0048731, P=9.16E-33), cellular process (GO:0009987, P= 5.52E-31), cell adhesion (GO:0007155, P= 8.63E-28) among others. Pathway analysis (PANTHER) indicated that the most overrepresented pathways were: cadherin signaling (P00012, P=6.62E-07), wnt signaling (P00057, P= 5.81E-06), integrin signaling (P00034, P= 1.09E-05) among others. In addition to gene expression analysis, we confirmed airway remodeling by histological examination (Hematoxylin and Eosin, Masson's trichrome staining) of lung sections at seven days from the last challenge (day 11). Conclusions: This is the first study showing a link between gene expression at whole-transcriptome level induced by chronic OGG1-BER (mimicked by multiple challenges with 8-oxoG) and airway remodeling, supported by histological structural changes in lungs. Balb/cJ mice (5 per group) were intranasally challenged with 8-oxoguanine (1 µM, 60 µl) for three times at days 0, 2 and 4. Control group mice were intranasally challenged with saline (60 µl). At 30, 60 and 120 min after the third challenge (day 4), mice were sacrificed and lungs were processed for RNA extraction. RNAs from individual mice within the same group were pooled and subjected to deep-sequencing analysis in duplicate using NSG on an Illumina HiSeq 1000 sequencing system. After alignment and processing, the resulting RPKM from treatment groups (8-oxoG-challenged) were normalized to control group (saline-challenged).

Dataset Information

Significant Contribution of DNA Repair Human 8-Oxoguanine DNA N-Glycosylase 1 Genotypes to Renal Cell Carcinoma.

Publications

Significant Contribution of DNA Repair <i>Human 8-Oxoguanine DNA N-Glycosylase 1</i> Genotypes to Renal Cell Carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets