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HOGG1 Ser326Cys polymorphism and risk of hepatocellular carcinoma among East Asians: a meta-analysis.

ABSTRACT: BACKGROUND: The hOGG1 gene encodes a DNA glycosylase enzyme responsible for DNA repair. The Ser326Cys polymorphism in this gene may influence its repair ability and thus plays a role in carcinogenesis. Several case-control studies have been conducted on this polymorphism and its relationship with the risk of hepatocellular carcinoma (HCC) among East Asians. However, their results are inconsistent. METHODS: We performed a meta-analysis of published case-control studies assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. PubMed, EMBASE, SCI, BIOSIS, CNKI and WanFang databases were searched. A random-effect model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses were conducted for additive, dominant and recessive genetic models. RESULTS: Eight studies were identified involving 2369 cases and 2442 controls assessing the association of the hOGG1 Ser326Cys polymorphism with HCC risk among East Asians. Applying a dominant genetic model, only in the Chinese population, the Cys allele was significantly associated with increased risk of HCC (OR 1.56, 95% CI 1.12-2.17). However, two studies influenced this finding according to sensitivity analysis. Furthermore, considerable heterogeneity and bias existed among Chinese studies. CONCLUSION: There is limited evidence to support that the hOGG1 Ser326Cys polymorphism is associated with HCC risk among East Asians. Well-designed and large-sized studies are required to determine this relationship.

SUBMITTER: Wang W

PROVIDER: S-EPMC3618171 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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hOGG1 Ser326Cys polymorphism and risk of hepatocellular carcinoma among East Asians: a meta-analysis.

Wang Wenjun W Dang Shuangsuo S Li Yaping Y Sun Mingzhu M Jia Xiaoli X Wang Rui R Liu Jingkun J

PloS one 20130405 4

<h4>Background</h4>The hOGG1 gene encodes a DNA glycosylase enzyme responsible for DNA repair. The Ser326Cys polymorphism in this gene may influence its repair ability and thus plays a role in carcinogenesis. Several case-control studies have been conducted on this polymorphism and its relationship with the risk of hepatocellular carcinoma (HCC) among East Asians. However, their results are inconsistent.<h4>Methods</h4>We performed a meta-analysis of published case-control studies assessing the ...[more]

PMID: 23577090

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Project description:Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. In this study, we tried to assess reported studies of association between polymorphism of human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys and lung cancer. We conducted MEDLINE, Current Contents and Web of Science searches using "hOGG1", "lung cancer" and "polymorphism" as keywords to search for papers published (from January 1995 through August 2010). Data were combined using both a fixed effects (the inverse variance-weighted method) and a random effects (DerSimonian and Laird method) model. The Cochran Q test was used for the assessment of heterogeneity. Publication bias was assessed by both Begg's and Egger's tests. We identified 20 case-control studies in 21 different ethnic populations. As two studies were not in the Hardy-Weinberg equilibrium, 18 case-control studies in 19 different ethnic populations (7,792 cases and 9,358 controls) were included in our meta-analysis. Summary frequencies of the Cys allele among aucasians and Asians based on the random effects model were 20.9% (95% confidence interval (CI) = 18.9-22.9) and 46.1% (95% CI = 40.2-52.0), respectively. The distribution of the Cys allele was significantly different between Asians and Caucasians (P < 0.001). The Cys/Cys genotype was significantly associated with lung cancer risk in Asian populations (odds ratio = 1.27, 95% CI = 1.09-1.48) but not in Caucasian populations. This ethnic difference in lung cancer risk may be due to environmental factors such as cigarette smoking and dietary factors. Although the summary risk for developing lung cancer may not be large, lung cancer is such a common malignancy that even a small increase in risk can translate to a large number of excess lung cancer cases. As lung cancer is a multifactorial disease, further investigations of the gene-gene and gene-environment interactions on the hOGG1 polymorphism-associated lung cancer risk may help to better understand of the molecular pathogenesis of human lung cancer.

Project description: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; P(heterogeneity) = 0.000), and recessive model: OR = 0.543; 95% CI = 0.399-0.739; P(heterogeneity) = 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; P(heterogeneity) = 0.064), and dominant model (OR = 0.160; 95% CI = 0.137-0.187; P(heterogeneity) = 0.001), and Caucasians for dominant model (OR = 1.35; 95% CI = 1.03-1.77; P(heterogeneity) = 0.015), and recessive model (OR = 1.35; 95% CI = 1.03-1.77; P(heterogeneity) = 0.015). In population-based populations, marginally significant increased risks were found in dominant model (OR = 0.143; 95% CI = 0.111 0.184; P(heterogeneity) = 0.000) and recessive model (OR = 0.429; 95% CI = 0.261-0.705; P(heterogeneity) = 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; P(heterogeneity )= 0.007),dominant model (OR = 0.122; 95% CI = 0.091-0.163; P(heterogeneity) = 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.

Dataset Information

HOGG1 Ser326Cys polymorphism and risk of hepatocellular carcinoma among East Asians: a meta-analysis.

Publications

hOGG1 Ser326Cys polymorphism and risk of hepatocellular carcinoma among East Asians: a meta-analysis.

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