The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk

Park, Jong; Chen, Lan; Tockman, Melvyn S.; Elahi, Abul; Lazarus, Philip

doi:10.1097/00008571-200402000-00004

Cited by 96 publications

(76 citation statements)

References 31 publications

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“…Results of a number of studies examining the role of the hOGG1 Ser326Cys polymorphism in lung cancer susceptibility conducted to date have been inconsistent. [7][8][9][10][11][12]17 Our case-control study showed a significant association between hOGG1 Ser326Cys polymorphism and lung cancer overall, supporting the potential effect of this polymorphism on lung cancer susceptibility. Because the question of whether the effect of this polymorphism differed by histology remained unanswered, we also conducted a meta-analysis with consideration to histology.…”

Section: Discussionsupporting

confidence: 56%

“…Among the 65 papers identified through this process, 7 were considered eligible. 5,[7][8][9][10][11]17 Two investigators (TO and KM) abstracted the data independently. We used OR from a random-effect model as a summary statistic for association.…”

Section: Meta-analysismentioning

confidence: 99%

“…Activity in the repair of 8-hydroxyguanine is greater with the hOGG1-Ser326 protein than the hOGG1-Cys326 protein, 5 and the possible contribution of this locus to the risk of a variety of human cancers has been reported. 6 A number of studies [7][8][9][10][11][12][13][14] and systematic approaches [15][16][17] have examined the role of the Ser326Cys polymorphism in lung cancer susceptibility. One meta-analysis showed that the overall odds ratio (OR) of homozygotes for the hOGG1-326Cys allele against those for the hOGG1-326Ser allele was 1.24 (95% confidence interval (CI)¼1.01-1.53), suggesting that the locus is involved in susceptibility to overall lung cancer.…”

Section: Introductionmentioning

confidence: 99%

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hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type

et al. 2009

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Human 8-oxoguanine DNA glycosylase 1 (hOGG1) has a major role in the repair of 8-hydroxyguanine, a major promutagenic DNA lesion. The genetic polymorphism rs1052133, which leads to substitution of the amino acid at codon 326 from Ser to Cys, shows functional differences, namely a decrease in enzyme activity in hOGG1-Cys326. Although several studies have investigated the association between rs1052133 and lung cancer susceptibility, the effect of this locus on lung cancer according to histology remains unclear. We therefore conducted a case-control study with 515 incident lung cancer cases and 1030 age-and sex-matched controls without cancer, and further conducted a meta-analysis. In overall analysis, the homozygous Cys/Cys genotype showed a significant association with lung cancer compared to Ser allele carrier status (odds ratio (OR)¼1.31, 95% confidence interval (CI)¼1.02-1.69). By histology-based analysis, the Cys/Cys genotype showed a significantly positive association with small-cell carcinoma (OR¼2.40, 95% CI¼1.32-4.49) and marginally significant association with adenocarcinoma (OR¼1.32, 95% CI¼0.98-1.77). A meta-analysis of previous and our present study revealed that this polymorphism is positively associated with adenocarcinoma, although suggestive associations were also found for squamousand small-cell lung cancers. These results indicate that rs1052133 contributes to the risk of adenocarcinoma of lung.

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Section: Discussionsupporting

confidence: 56%

Section: Meta-analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type

et al. 2009

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“…The potential mechanism of carcinogenesis in the lung tissue may involve tissue damage and regeneration in the presence of a high ROS release from inflammatory cells that can interact with DNA in epithelial cells to produce permanent genomic mutations (27). One of them, 8-OHG is a mutagenic and most common oxidative modification of guanine, and has a pivotal role in the development of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

The Association of OGG1 Ser326Cys Polymorphism and Urinary 8-OHdG Levels With Lung Cancer Susceptibility: A Hospital-Based Case-Control Study in Turkey

Karahalıl

Emerce

Koçer

et al. 2008

Archives of Industrial Hygiene and Toxicology

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High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.

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“…8-OxoG itself is mildly mutagenic and forms G:C → T:A transversion mutations approximately half the time during DNA replication in vitro (22,(30)(31)(32)(33) but only about 5% of the time in vivo (31). The hOGG1 base excision repair pathway is the primary route for the excision and repair of 8-oxoG in human DNA, and genetic polymorphisms of this repair enzyme have been associated with increased risk of lung cancer (50). However, Ogg1 knockout mice have shown no change in the observable phenotype relative to wild-type mice, although a slight increase in mutation rate was observed in some tissues (51,52).…”

Section: Formation Of 8-oxog In the Cr(vi)/asc Oxidation Reactionmentioning

confidence: 99%

Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2‘-deoxyguanosine

Slade

Hailer

Martin

et al. 2005

Chem. Res. Toxicol.

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7,8-dihydro-8-oxoguanine (8-oxoG) is thought to be a major lesion formed in DNA by oxidative attack at the nucleobase guanine. Recent studies have shown that 8-oxoG has a lower reduction potential than the parent guanine and is a hot spot for further oxidation. Spiroiminodihydantoin (Sp) has been identified as one of these further oxidation products. Chromium(VI) is a human carcinogen that, when reduced by a cellular reductant such as ascorbate, can oxidize DNA. In this study, duplex DNA was reacted with Cr(VI) and ascorbate to identify and quantify the base lesions formed. Guanine bases were observed to be preferentially oxidized with 5′ guanines within purine repeats showing enhanced oxidation. Trapping of the guanine lesions by the base excision repair enzymes hOGG1 and mNEIL2 showed nearly exclusive trapping by mNEIL2, suggesting that 8-oxoG was not the major lesion but rather a lesion recognized by mNEIL2 such as Sp. Formation of the Sp lesion in the Cr(VI)/Asc oxidation reaction with DNA was confirmed by LC-ESI-MS detection. HPLC-ECD was used to identify and quantify any 8-oxoG arising from Cr(VI)/Asc oxidation of DNA. Concentrations of Cr(VI) (3.1-50 μM) with a corresponding 1:10 ratio of Asc oxidized between 0.3% and 1.5% of all guanines within the duplex DNA strand to Sp. 8-oxoG was also identified but with the highest Cr (VI) concentration converting ~0.1% of all guanines to 8-oxoG. These results show that Sp was present in concentrations ~20 times greater than that of 8-oxoG in this system. The results indicate that 8-oxoG, while present, was not the major product of Cr(VI)/Asc oxidation of DNA and that Sp predominates under these conditions. These results further imply that Sp may be the lesion that accounts for the carcinogenicity of this metal in cellular systems.

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The human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) DNA repair enzyme and its association with lung cancer risk

Abstract: These results suggest that the hOGG1 Ser326Cys polymorphism plays an important role in the risk for lung cancer and is linked to exposure to tobacco smoke.

Cited by 96 publications

References 31 publications

hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type

hOGG1 Ser326Cys polymorphism and risk of lung cancer by histological type

The Association of OGG1 Ser326Cys Polymorphism and Urinary 8-OHdG Levels With Lung Cancer Susceptibility: A Hospital-Based Case-Control Study in Turkey

Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2‘-deoxyguanosine

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