Objectives: Exploring the relationship between the hOGG1 rs1052133 polymorphism and the occurrence of nasopharyngeal carcinoma (NPC). Methods: PubMed, Web of Science, Scopus, CNKI, Wanfangdata, and VIP were used to search for studies and the NOS evaluation scale was used to evaluate the quality. All studies were grouped according to different genotypes. The Cochrane\'s Q test and I2 test were used for heterogeneity evaluations. If heterogeneity was small, the fixed effects model was used, and conversely, the random effects model was used. Publication bias was also detected. P < .05 in all results indicated statistically significant. Results: We ultimately included 6 studies with 2021 NPC patients in the study group and 2375 healthy populations in the control group. After meta-analysis, it was found that the total OR value of the \"Ser/Cys (CG) vs Ser/Ser (CC)\" group was 1.00 (95% CI: 0.85-1.18) and the \"Cys/Cys (GG) vs Ser/Ser (CC)\" group was 1.06 (95% CI: 0.87-1.28). These results were not statistically significant (P > .05). Furthermore, the integrated total OR values of each group were not statistically significant with or without the smoking history, even in other genotype models (Allele, Dominant, Recessive, and Additive) (P > .05). Conclusion: There is no clear correlation between the hOGG1 rs1052133 polymorphism and the occurrence of NPC, even with or without the smoking history.

BACKGROUND: Human 8-oxoG DNA glycosylase 1 (hOGG1) is one of the important members of DNA glycosylase for Base excision repair (BER), the abnormal activity of which can lead to the failure of BER and the appearance of various diseases, such as breast cancer, bladder cancer, Parkinson\'s disease and lung cancer. Therefore, it is important to detect the activity of hOGG1. However, traditional detection methods suffer from time consuming, complicated operation, high false positive results and low sensitivity. Thus, it remains a challenge to develop simple and sensitive hOGG1 analysis strategies to facilitate early diagnosis and treatment of the relative disease.
RESULTS: A target-induced rolling circle amplification (TIRCA) strategy for label-free fluorescence detection of hOGG1 activity was proposed with high sensitivity and specificity. The TIRCA strategy was constructed by a hairpin probe (HP) containing 8-oxoG site and a primer probe (PP). In the presence of hOGG1, the HP transformed into dumbbell DNA probe (DDP) after the 8-oxoG site of which was removed. Then the DDP formed closed circular dumbbell probe (CCDP) by ligase. CCDP could be used as amplification template of RCA to trigger RCA. The RCA products containing repeated G4 sequences could combine with ThT to produce enhanced fluorescence, achieving label-free fluorescence sensing of hOGG1. Given the high amplification efficiency of RCA and the high fluorescence quantum yield of the G4/ThT, the proposed TIRCA achieved highly sensitive measurement of hOGG1 activity with a detection limit of 0.00143 U/mL. The TIRCA strategy also exhibited excellent specificity for hOGG1 analysis over other interference enzymes.
CONCLUSIONS: This novel TIRCA strategy demonstrates high sensitivity and high specificity for the detection of hOGG1, which has also been successfully used for the screening of inhibitors and the analysis of hOGG1 in real samples. We believe that this TIRCA strategy provides new insight into the use of the isothermal nucleic acid amplification as a useful tool for hOGG1 detection and will play an important role in disease early diagnosis and treatment.

Noise exposure is a health hazard in the textile industry. In cochlear hair cells, DNA damage caused by 8-oxoguanine (8-oxo G) can result in noise-induced hearing loss. Human 8-hydroxyguanine glycosylase (hOGG1) is a DNA repair enzyme that excises (8-oxo G) in the DNA and repairs DNA damage. Glutathione peroxidase-1 (GPx) is a crucial antioxidant enzyme that aids in limiting cochlear damages. Heme oxygenase-1 (HO-1) is a stress-inducible protein with a high fold change in the hair cells of the cochlea. The study aimed to investigate the association of either hOGG1 and GPx-1 polymorphisms with audiometric notches and HO-1 protein among textile workers. hOGG1 and GPx genotypes were analyzed by PCR-RFLP, and HO-1 levels were measured by ELISA in 115 male textile workers. Blood pressure and audiogram were performed. Results recorded the relation between audiometric notches and ear complaints among workers. Older age workers showed audiometric notches at > 25 dB with a significant decrease in HO-1 levels and higher levels in workers with normal audiogram. Ser/Cys genotype of hOGG1 gene was associated with age and work duration while CC genotype of GPx is associated with HO-1 levels and diastolic pressure. Ser/Cys genotype of hOGG1 gene was associated with age while Cys/Cys genotype was associated with work duration among workers. CC genotype of GPx gene was associated with higher HO-1 levels and TT genotype was associated with high diastolic pressure. Finally, hearing impairment was dependent on the duration of exposure to noise, older age, and the presence of heterozygote TC genotype of GPx gene among textile workers.

Human 8-oxoguanine DNA glycosylase (hOGG1) and flap endonuclease 1 (FEN1) are recognized as potential biomarkers in lung cancer investigations. Developing analytical platforms of simultaneously targeting hOGG1 and FEN1 with high selectivity, sensitivity, especially programmability and universality is highly valuable for clinical research. Herein, we established a signal-amplified platform for simultaneously detecting hOGG1 and FEN1 on the basis of cleavage-induced ligation of DNA dumbbell probes, rolling circle transcription (RCT) and CRISPR-Cas12a. A hOGG1 cleavable site and FEN1 cleavable flap were dexterously designed at the 5\' end of DNA flapped dumbbell probes (FDP) for hOGG1 and FEN1. After cleavage, the resulting nick sites with juxtaposition of 5\' phosphate and 3\' hydroxyl terminus could be linked to closed DNA dumbbell probes (CDP) by DNA ligase. The CDP served as a template for RCT, producing plentiful crRNA repeats to activate the trans-cleavage activity of CRISPR-Cas12a which could cleave fluorophores (TAMRA and FAM) and quenchers (BHQ2 and BHQ1) double-labeled ssDNA reporters. Then, hOGG1 and FEN1 could be detected by the recovered fluorescence signal, allowing for the highly sensitive calculated detection limits of 0.0013 and 0.0052 U/mL, respectively. Additionally, this method made it possible to evaluate the inhibitory effects, even to measure hOGG1 and FEN1 activities at the single-cell level. This novel target enzyme-initiated, circles-transcription without promoters, real-time generation, and self-assembly features of FDP-RCT-Cas12a system suppressed nonspecific background remarkably and relieved rigorous requirement of protospacer adjacent motif site. Hence, the universality of FDP-RCT-Cas12a system toward various disease-related non-nucleic acid targets which are tested without using aptamers was extremely improved.

In current work, with elaborate designs of G-quadruplex containing \"Y\" junction structures, we demonstrate the construction of several new and label-free electrochemical logic gate operations (OR, AND, NOR, and NAND) by defining two distinct biomolecules, human 8-oxo-7,8-dihydroguanine DNA glycosylase 1 (hOGG1) and microRNA-141 (miRNA-141), as the inputs. The \"Y\" junction structures are immobilized onto the surface of gold electrode as the signal transduction platform. The presence of the input molecules with different combinations can alter the \"Y\" junction structures to disrupt the formation of the complete G-quadruplexes via 8-oxoG-site specific cleavage and miRNA-141-triggered displacement of the \"Y\" junctions. Subsequent association of hemin with the G-quadruplex sequences thus yields significant current variation outputs upon electrochemical reduction of hemin on the electrode, leading to the successful function of different logic operations without the involvement of labeling the DNA sequences with electro-active species. Featured with the advantages of multiple logic operations with distinct inputs and the label-free electrochemical format, such molecular logic gates can potentially provide promising opportunities for the development of simple and robust biological logic gates for various applications.

7,8-dihydro-8-oxoguanine (8-oxoG) is one of the most common and mutagenic oxidative DNA damages induced by reactive oxygen species (ROS). Since ROS is mainly produced in the inner membranes of the mitochondria, these organelles and especially the mitochondrial DNA (mtDNA) contained therein are particularly affected by this damage. Insufficient elimination of 8-oxoG can lead to mutations and thus to severe mitochondrial dysfunctions. To eliminate 8-oxoG, the human body uses the enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which is the main antagonist to oxidative damage to DNA. However, previous work suggests that the activity of the human OGG1 (hOGG1) decreases with age, leading to an age-related accumulation of 8-oxoG. A better understanding of the exact mechanisms of hOGG1 could lead to the discovery of new targets and thus be of great importance for the development of preventive therapies. Because of this, we developed a real-time base excision repair assay with a specially designed double-stranded reporter oligonucleotides to measure the activity of hOGG1 in lysates of isolated mitochondria. This system presented here differs from the classical assays, in which an endpoint determination is performed via a denaturing acrylamide gel, by the possibility to measure the hOGG1 activity in real-time. In addition, to determine the activity of each enzymatic step (N-glycosylase and AP-lyase activity) of this bifunctional enzyme, a melting curve analysis can also be performed. After isolation of mitochondria from human fibroblasts using various centrifugation steps, they are lysed and then incubated with specially designed reporter oligonucleotides. The subsequent measurement of hOGG1 activity is performed in a conventional real-time PCR system.

The association between the hOGG1 Ser326Cys polymorphism and gynecologic cancer susceptibility is inconclusive. We performed a comprehensive meta-analysis to precisely estimate of the impact of the hOGG1 Ser326Cys polymorphism on gynecologic cancer susceptibility. Electronic databases including PubMed, Embase, WanFang, and the China National Knowledge Infrastructure were searched for relevant studies. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were determined to assess the strength of the association. Fourteen studies with 2712 cases and 3638 controls were included in the final meta-analysis. The pooled analysis yielded a significant association between the hOGG1 Ser326Cys polymorphism and overall gynecologic cancer susceptibility (dominant model: OR = 1.16, 95% CI = 1.03-1.30, P=0.017). A significantly higher gynecologic cancer risk was found for the European population (homozygous model: OR = 2.17, 95% CI = 1.80-2.61, P<0.001; recessive model: OR = 2.11, 95% CI = 1.41-3.17, P<0.001; dominant model: OR = 1.29, 95% CI = 1.12-1.48, P<0.001; and allele model: OR = 1.40, 95% CI = 1.13-1.74, P=0.002), but not in the Asian population. The stratified analysis by cancer type revealed endometrial cancer was significantly associated with the hOGG1 Ser326Cys polymorphism (dominant model: OR = 1.29, 95% CI = 1.09-1.54, P=0.003; and allele model: OR = 1.28, 95% CI = 1.02-1.60, P=0.031). In conclusion, the hOGG1 Ser326Cys polymorphism was associated with higher overall gynecologic cancer susceptibility, especially for endometrial cancer in the European population.

Identification of modifier genes predisposing to breast cancer (BC) phenotype remains a significant challenge and varies with ethnicity. The genetic variability observed in DNA repair genes may modulate the cell\'s ability to repair the damaged DNA and hence, evaluation of genetic variants in crucial DNA damage repair genes is of clinical importance. We performed the present study to evaluate the role of ERCC2-Lys751Gln, hOGG1-Ser326Cys, and XRCC1-Arg399Gln gene polymorphisms on the risk of BC development and its molecular profile in Indian women. Three non-synonymous variants (rs13181, rs1052133, and rs25487) were genotyped in 464 BC patients and 450 healthy controls. Logistic regression was employed to evaluate the association of genotypes with BC risk. Also, in silico analysis was carried out to map the Arg399Gln variant on the BRCT1 domain of XRCC1 protein. XRCC1 Gln/Gln genotype frequency was significantly elevated in BC patients [odd ratio (OR) = 1.73; 95% confidence interval (CI) = 1.13-2.65]. No significant association was observed between hOGG1-Ser326Cys and ERCC2-Lys751Gln variants and BC risk. Subgroup analysis revealed that ERCC2-Lys751Gln and XRCC1-Arg399Gln variants contributed towards tumor progression. A positive interaction between the investigated SNPs and BC was revealed by MDR analysis. Arg399Gln variant resulted in a change in the surface charge of XRCC1 protein. The rs25487 variant of XRCC1 might be associated with an elevated risk of BC. Furthermore, we demonstrated that high order gene-gene interaction plays a significant role in BC etiology. Hence, understanding the impact of low penetrant gene polymorphisms might enable a better understanding of the genetic background of breast cancer.

BACKGROUND: 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.
CONCLUSIONS: 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.

The DNA of human cells suffers about 1.000-100.000 oxidative lesions per day. One of the most common defects in this category is represented by 7,8-dihydro-8-oxoguanine. There are numerous exogenous effects on DNA that induce the intracellular generation of 7, 8-dihydro-8-oxoguanine. Therefore, a quantitatively sufficient repair of all occurring oxidative damaged guanine bases is often only partially feasible, especially in advanced age. Inadequate removal of these damages can subsequently lead to mutations and thus to serious diseases. All these aspects represent a dangerous situation for an organism. However, it is suspected that the amount of the 8-oxoguanine DNA glycosylase can be actively regulated on the level of gene expression by the redox-active properties of ubiquinol and thus its protein expression can be controlled. Using an real-time base excision repair assay including a melting curve analysis, the activity of the human 8-oxoguanine DNA glycosylase 1 was measured under the influence of ubiquinol. It was possible to observe a concentration-dependent increase in the activity of the 8-oxoguanine DNA glycosylase 1 under the influence of ubiquinol for the first time, both on purified and commercially acquired enzyme as well as on enzyme isolated from mitochondria of human fibroblasts. An increase in activity of this enzyme based on a change in cellular redox state caused by ubiquinol could not be confirmed. In addition, an increased gene expression of 8-oxoguanine-DNA glycosylase 1 under ubiquinol could not be observed. However, there was a change in bifunctionality in favor of an increased N-glycosylase activity and a direct interaction between ubiquinol and 8-oxoguanine DNA glycosylase 1. We suggest that ubiquinol contributes to the dissolution of a human 8-oxoguanine DNA glycosylase 1 end-product complex that forms after cutting into the sugar-phosphate backbone of the DNA with the resulting unsaturated 3\'-phospho-α, β-aldehyde end and thereby inhibits further enzymatic steps.