We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide base repair (BER) pathway, focusing on 8-oxoguanine DNA glycosylase 1, X-ray cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1.
Multiple logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the risk of p53 mutation associated with polymorphisms of hOGG1 and APE1 in lung cancer.
Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a role in predisposition to lung cancer.
To analyze the relationship of GSTT1, GSTM1, XRCC1 (rs25487), ERCC1 (rs11615, rs3212986), ERCC2 (rs13181), XRCC3 (rs861539), OGG1 (rs1052133), and Alpha-1-Antitrypsin mutations (AAT) with the risk of lung cancer in never-smokers, and ascertain if there is an effect modification between these polymorphisms and residential radon exposure.
For example, there was a positive association between the OGG1Ser326Cys variant and gastric and lung cancer, while the XRCC1 Arg399Gln variant was associated with reduced cancer risk.
In a hospital-based, case-control study of 455 lung cancer cases and 443 cancer-free hospital controls, the SNPs of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their correlation with the risk of lung cancer in multivariate logistic regression models.
In the present study, we investigated the polymorphisms of the following selected members of the base and nucleotide excision repair genes: XPC (Lys939Gln), XPD (Lys751Gln), XRCC1(Arg399Gln), and hOGG1(Ser326Ser), and the risk they present toward the development of lung cancer, with emphasis on the effect of chromium exposure.
In our study, the possibility of an association of CYP1B1, GSTP1 and hOGG1 genetic polymorphisms with lung cancer was investigated in Chinese population of Nanjing, by a new single nucleotide polymorphism (SNP) typing approach of di-allele-specific-amplification with artificially modified primers (diASA-AMP) technique.
Some studies find positive associations between lung cancer and variations in the human 8-oxoguanine DNA glycosylase (hOGG1) gene that encodes a major DNA glycosylase for oxidized lesions with sluggish kinetics properties.
They found increased lung cancer risk among subjects carrying the OGG1 Cys/Cys genotype (odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.01, 1.53), using 3,253 cases and 3,371 controls from seven studies; this is consistent with experimental evidence that this isoform exhibits decreased activity.
We further demonstrated that bleomycin-induced DNA strand breaks resulted in an increase of micronucleus rate. hOGG1 deficiency significantly reduced DNA damage repair capacity of the lung cancer cell lines.
We employed a population-based case-control study of 122 cases and 122 controls to investigate the effect that green tea consumption may have on the risk of lung cancer and whether polymorphisms in 8-oxoguanine-DNA glycosylase (OGG1), glutathione-S-transferase M1 (GSTM1), and aldo-keto reductase 1C3 (AKR1C3) modify such an association.
It has been previously reported that smokers with low hOGG1 activity had significantly higher risk of developing lung cancer as compared to smokers with high hOGG1 activity.
Both the XRCC1 Arg194Trp and Arg280His as well as the OGG1Ser326Cys heterozygous genotypes were associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024; OR=0.25, p=0.028; OR=0.51, p=0.033, respectively).
The overall odds ratio for lung cancer among those with the OGG1 Cys/Cys genotype compared with those with the OGG1 Ser/Ser genotype was 1.34 (95% CI = 0.95 to 1.88); the association was most prominent for adenocarcinoma risk (OR = 1.66, 95% CI = 1.04 to 2.66).
Thus, analysis of the mechanism by which OGG1 modulates gene expression helps discern between beneficial and detrimental effects of oxidant stress, exposes a missing functional link as a marker, and yields a novel target for lung cancer.
Case-control studies of genetic polymorphisms in DNA repair enzymes suggest that the common variant Ser326Cys in OGG1 may be a risk factor for lung cancer, whereas a rare variant in OGG1 and germ line mutations in the corresponding mismatch repair gene MYH are risk factors for hereditary colon cancer.
These results suggest that SNPs in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population, particularly among heavily exposed women.
In a nested case-cohort design we examined associations between urinary excretion of 8-oxoGua and risk of lung cancer as well as potential interaction with the OGG1Ser326Cys polymorphism in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years with 3-7 years follow-up.
Importantly, it can be applied for the detection of enzyme kinetic parameters, the screening of hOGG1 inhibitors, and the quantification of hOGG1 activity in even 1 single lung cancer cell, providing a new approach for biomedical research and clinical diagnosis.
A combined MPG and OGG1 activities score was more strongly associated with lung cancer risk than either activity alone, with an odds ratio of 2.3 (95% CI = 1.4 to 3.6; P < .001).