Association Of hOGG1 Ser326Cys Polymorphism Research Articles

Association of hOGG1-Cys variants with occurrence of p53 and EGFR deletion mutations in non-small cell lung cancer.

BackgroundThe human 8‐oxoguanine DNA glycosylase 1 (hOGG1) gene encodes a DNA glycosylase that removes 8‐hydroxy‐2‐deoxyguanine (8‐OH‐dG) DNA damage to protect against gene mutations. The association of hOGG1 Ser326Cys polymorphism with lung cancer risk has predicted that hOGG1‐Cys variants are less effective at removing 8‐OH‐dG damage from DNA; therefore, these variants might show an increased occurrence of tumor suppressor gene and oncogene mutations. However, no evidence has yet supported this hypothesis.MethodsDirect sequencing was performed to examine the mutations of p53 and EGFR genes in lung tumors from patients with non‐small cell lung cancer (NSCLC). Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) was used to examine hOGG1 Ser326Cys polymorphism in this study population.ResultsA total of 99 p53‐mutated and 99 EGFR‐mutated patients with NSCLC were selected to explore the possible associations of these mutations with hOGG1 Ser326Cys polymorphism. The p53‐mutated and EGFR‐mutated patients were divided into nondeletion and deletion subgroups. P53 deletion mutations were more commonly observed in male than in female patients (P = 0.030). However, EGFR exon 19 deletion mutations were more prevalent in female and adenocarcinoma patients than in male and squamous cell carcinoma patients (P = 0.028 for genders, P = 0.017 for tumor histology). Interestingly, p53 and EGFR exon 19 deletion mutations were more frequent in patients with hOGG1 Ser/Cys + Cys/Cys hOGG1‐Cys variants than with the hOGG1 Ser/Ser genotype (P = 0.010 for p53, P = 0.032 for EGFR).ConclusionsWe suggest that the association of hOGG1 Ser326Cys polymorphism with lung cancer risk could be partially explained by increases in p53 and EGFR deletion mutations.Key pointsSignificant findings of the study NSCLC patients with hOGG1‐Cys variants may have a higher risk of p53 and EGFR deletion mutations than with hOGG1 Ser/Ser genotype. What this study adds NSCLC patients with hOGG1‐Cys variants might be helpful to predict patients having higher risk of EGFR exon 19 deletion mutations and these patients who were treated with gefitinib or erlotinib could be a higher risk to occur EGFR T790M mutation.

Association of hOGG1 Ser326Cys polymorphism with colorectal cancer risk: an updated meta-analysis including 5235 cases and 8438 controls.

It has been suggested that hOGG1 Ser326Cys polymorphism may be a risk factor for colorectal cancer. Published data on its association with colorectal cancer generated contradictory results; thus, we performed an updated meta-analysis of eligible published studies to estimate the effect of hOGG1 Ser326Cys polymorphism on colorectal cancer susceptibility. We reviewed many abstracts and finally included 18 eligible case-control studies comprising 5235 cases and 8438 controls. We pooled data with a fixed or random-effect model. Subgroup analysis by ethnicity was also performed. The overall data indicated a significant association of hOGG1 Ser326Cys polymorphism on colorectal cancer risk (allele model OR = 1.14, 95%CI 1.02-1.27; homozygote model OR = 1.32, 95%CI 0.92-1.92; recessive model OR = 1.12, 95%CI 1.00-1.26; dominant model OR = 1.15, 95%CI 1.00-1.32). Furthermore, in the subgroup analysis by ethnicity, increased cancer risk was observed among Caucasians under the allele, heterogeneity, recessive, and dominant models (allele model OR = 1.23, 95%CI = 1.05-1.44; homozygote model OR = 1.49, 95%CI 1.05-2.12; recessive model OR = 1.40, 95%CI 1.16-1.69; dominant model OR = 1.21, 95%CI = 1.12-1.45). In summary, the present meta-analysis suggested that hOGG1 Ser326Cys polymorphism might modify the susceptibility to colorectal cancer among the total population, especially among Caucasians.

Erratum to: Association of hOGG1 Ser326Cys polymorphism with gastric cancer risk: a meta-analysis

Erratum to: Association of hOGG1 Ser326Cys polymorphism with gastric cancer risk: a meta-analysis

The hOGG1 Ser326Cys Gene Polymorphism and the Risk of Coronary Ectasia in the Chinese Population

Oxidative stress (OS) is related to vascular inflammation possibly, contributing to the development of coronary ectasia (CE). Base excision repair (BER) and nucleotide excision repair are the main DNA repair pathways that can help to remove 8-hydroxydeoxyguanine (8-OHdG), a marker of OS. Human 8-oxoguanine DNA glycosylase 1 (hOGG1) is a key enzyme of the BER pathway and catalyzes the removal of 8-OHdG. The aim of our study was to investigate the association between hOGG1 Ser326Cys gene polymorphism and CE in a Chinese population. Five-hundred forty-seven patients who underwent diagnostic coronary angiography in a tertiary medical center were recruited. The angiographic definition of CE is the diameter of the ectatic segment being more than 1.5 times larger compared with an adjacent healthy reference segment. The gene polymorphisms were analyzed by polymerase chain reaction. The urine 8OHdG concentration was measured using a commercial ELISA kit. The distribution of hOGG1 Ser326Cys genotypes was significantly different between CE and non-CE groups (p = 0.033). The odds ratio of CE development for the Ser to the Cys variant was 1.55 (95% confidence interval (CI), 1.04–2.31, p = 0.033). Both univariate and logistic regression analysis showed a significant association of hOGG1 Ser326Cys polymorphism in the dominant model with CE development (p = 0.009 and 0.011, respectively). Urine 8-OHdG levels were significantly higher in subjects carrying the hOGG1 Ser variant than in those with the Cys/Cys genotype (p < 0.03). In conclusion, our study suggests that the hOGG1 Ser326Cys gene variant might play a role in susceptibility to the development of CE.

Association between the hOGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis based on 22,475 subjects

ObjectivesThe Ser326Cys polymorphism in the human 8-oxogunaine glycosylase (hOGG1) gene with lung cancer susceptibility had been investigated, but results were inconsistent and underpowered. The aim of this study was to conduct a meta-analysis assessing the association of hOGG1 Ser326Cys polymorphism with risk of lung cancer.Materials and methodsRelevant studies were identified through a search of MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature database (CBM) using terms “lung cancer”, “hOGG1” or “OGG1”, “polymorphism” or “variation” and the last search updated on May 1, 2013. In this meta-analysis, we assessed 30 published studies involving 22,475 subjects that investigated the association between the hOGG1 Ser326Cys polymorphism and lung cancer susceptibility.ResultsOverall, the hOGG1 Ser326Cys polymorphism was not associated with lung cancer susceptibility in different genetic models (dominant model comparison: OR = 0.133; 95% CI = 0.111–0.161; Pheterogeneity = 0.000), and recessive model: OR = 0.543; 95% CI = 0.399–0.739; Pheterogeneity = 0.000). Similarly, in the stratified analyses by ethnicity, significantly increased risks were found among Asians for homozygote comparison (OR = 0.850; 95% CI = 0.732 0.986; Pheterogeneity = 0.064), and dominant model (OR = 0.160; 95% CI = 0.137–0.187; Pheterogeneity = 0.001), and Caucasians for dominant model (OR = 1.35; 95% CI = 1.03–1.77; Pheterogeneity = 0.015), and recessive model (OR = 1.35; 95% CI = 1.03–1.77; Pheterogeneity = 0.015). In population-based populations, marginally significant increased risks were found in dominant model (OR = 0.143; 95% CI = 0.111 0.184; Pheterogeneity = 0.000) and recessive model (OR = 0.429; 95% CI = 0.261–0.705; Pheterogeneity = 0.000). We also found a significant difference between hOGG1 Ser326Cys genotype and lung cancer susceptibility in studies with hospital-based controls for homozygote model (OR = 0.798; 95% CI = 0.649–0.982; Pheterogeneity = 0.007),dominant model (OR = 0.122; 95% CI = 0.091–0.163; Pheterogeneity = 0.000).ConclusionOur data showed that the hOGG1 Ser326Cys polymorphism contributed to the risk of lung cancer.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3842531131031605

Association of hOGG1 Ser326Cys polymorphism with gastric cancer risk: a meta-analysis

Studies investigating the association between human 8-oxoguanine glycosylase 1(hOGG1) Ser326Cys polymorphism and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case-control studies to better compare results between studies. 11 eligible studies with 2,180 GC cases and 3,985 controls were selected. There were 5 studies involving Caucasians and 5 studies involving Asians. The combined result based on all studies did not show significant difference in any genetics models. Ser/Cys + Cys/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.81-1.03), Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.07, 95% CI 0.80-1.44), Ser/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.80-1.03), Sys/Cys versus Ser/Cys (OR = 1.10, 95% CI 0.83-1.47), Cys/Cys versus Ser/Ser (OR = 0.99, 95% CI 0.74-1.34), Cys versus Ser (OR = 1.01, 95% CI 0.88-1.17).When stratifying for ethnicity, there was still no significant association found between hOGG1 Ser326Cys polymorphism and GC risk. Funnel plot and Egger’s test showed some evidence of publication bias on the basis of all studies. Two studies were the main reason because their samples were too small. However, the result of sensitivity analysis suggested that the influence of these two studies and one mixed population study on the pooled OR was weak. Our result could explain the association between hOGG1 Ser326Cys polymorphism and GC risk. In conclusion, we did not found the evidence that the Cys allele at codon 326 of hOGG1 could increase GC risk in our analysis.

Lack of Association between hOGG1 Ser326Cys Polymorphism and the Risk of Bladder Cancer: A Meta-Analysis

Objective: In some but not all studies, hOGG1 Ser326Cys polymorphism has been reported to contribute to the risk of bladder cancer. To determine whether there is a significant association of hOGG1 Ser326Cys polymorphism with the susceptibility for bladder cancer, we performed a comprehensive meta-analysis. Methods: The electronic PubMed, Medline and Springer databases were searched for publications on the association between hOGG1 Ser326Cys polymorphism and bladder cancer through to May 20, 2011. Seven case-control studies were identified, including 2,474 cases and 2,408 controls. From these identified publications, crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of association using fixed- or random-effects models. Two investigators each extracted data and conducted the analysis independently. Results: Overall, no significant associations were found between hOGG1 Ser326Cys polymorphism and bladder cancer in codominant models (GG vs. CC: OR 1.11, 95% CI 0.74–1.66, p = 0.63; GC vs. CC: OR 1.07, 95% CI 0.80–1.41, p = 0.65). Similarly, no significant associations with bladder cancer were observed in the recessive model (GG vs. GC+CC: OR 1.05, 95% CI 0.65–1.70, p = 0.85), dominant model (GG+GC vs. CC: OR 1.07, 95% CI 0.87–1.32, p = 0.53) and allele model (G vs. C: OR 1.06, 95% CI 0.90–1.26, p = 0.49). In the stratified analyses by ethnicity, control sources, pathology, Hardy-Weinberg equilibrium, significant associations were still not observed. Conclusions: The overall current literature on hOGG1 Ser326Cys polymorphism and the risk of bladder cancer suggests no statistically significant association between the two. Additional primary studies may be necessary to provide evidence of any significant association between this specific polymorphism and bladder cancer.

Meta analysis of association between Ser326Cys polymorphism of hOGG1 gene and risk of lung cancer

背景与目的就全世界范围内而言，肺癌是一种常见疾病。人8-羟基鸟嘌呤糖苷酶（human 8-hydroxyguanine glycosylase, hOGG1）是一种DNA修复酶，它能特异切除8-羟基鸟嘌呤（8-dihydro-8-oxoguanine, 8-OH-G），对损伤的DNA进行修复。hOGG1 Ser326Cys基因多态性与癌症易感性的关系一直是研究的热点，而该多态性与肺癌易感性的关系尚存在争议。本研究采用meta分析旨在更好地探讨hOGG1 Ser326Cys多态性与肺癌易感性之间的关系。方法使用MEDLINE数据库检索2010年11月以前的相关文献，按照纳入标准，全面搜索含有研究hOGG1 Ser326Cys多态性与肺癌易感性相关的信息。由至少两位评论员做独立文献筛选和资料提取，并交叉审核。使用STATA 10.1软件进行统计分析。结果根据检索条件，共有22篇文献（包括8, 575例肺癌患者和9, 484名正常对照个体）被纳入当前的meta分析。分析结果表明22项研究的结果存在明显异质性，当排除不符合Hard-Weinberg平衡定律的两篇文献后，其余的文献呈现出较好的同质性。与hOGG1 Ser326相比，Cys326基因型明显增加了肺癌发病风险（OR=1.24, 95%CI:1.10-1.39, P < 0.001）。这种正相关在亚洲人群和医院来源的样本中尤为明显（OR=1.28, 95%CI: 1.11-1.49; OR=1.26, 95%CI: 1.09-1.46）。结论hOGG1 Ser326Cys多态性与肺癌易感性之间存在明显相关性，Cys326基因型能明显增加肺癌发病风险。