This preliminary study may provide initial information on the hOGG1 mRNA level of peripheral blood cells as a biomarker in epidemiological studies on oxygen radicals, oxygen radical-related agents, and cancer.
Given the crucial role of the APEX and OGG1 proteins in BER of oxidative DNA damage, the identified polymorphisms are good candidates for genetic epidemiologic studies of cancer susceptibility, while the finding that three of 20 (15%) endometrial tumors have somatic mutations in APEX suggests that inactivation of the BER pathway is important for the development of endometrial cancer in at least a subset of cases.
This study supported the first study by Sugimura et al (Cancer Epidemiol Biomarkers Prev, 1999; 8: 669-674), that the association of OGG1Ser326Cys polymorphism was limited for the risk of lung adenocarcinoma.
Nonetheless, published data were consistent with associations between: (a) the OGG1S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer.
Although hNTH1, hOGG1, and hMYH account for major cellular glycosylase activity for inherent substrate lesions, mouse models deficient in the enzymes exhibit no overt phenotypes such as the development of cancer, implying backup mechanisms.
Genetic analysis of the OGG1 gene reveals that both PC-3 and DU-145 cell lines harbor polymorphisms associated with a higher susceptibility to certain cancers.
These findings suggest that attenuated OGG1 expression contributes to 8-oxoG accumulation under oxidative stress, resulting in cancer development in the esophagus.
The authors conducted meta-analyses of associations between genes in the base excision repair pathway and cancer risk, focusing on three key genes: 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease (APE1/APEX1), and x-ray repair cross-complementing group 1 (XRCC1).
In studies that explored potential interactions with environmental factors, cancer risk for hOGG1 genotypes differed depending on exposure, especially for colon cancer.
It seems that there is a growing need for extensive genotype studies with respect to the hOGG1 gene due to its importance to various types of cancer and to smoking habits.
Mice null for oxoguanine DNA glycosylase (OGG1) are deficient in 8-oxodG removal and accumulate 8-oxodG in mtDNA to levels 20-fold higher than in wild-type mice (N.C. Souza-Pinto et al., 2001, Cancer Res.61, 5378-5381).
Therefore, the possible association of the hOGG1Ser326Cys gene variant with insulin sensitivity was investigated in 279 normal glucose-tolerant subjects without history of cancer.
Case-control studies to date suggest that the OGG1-326Cys allele is associated with a higher risk for several types of cancers, including overall lung cancer.
Base excision repair (BER) genes (X-ray repair cross complementing 1, XRCC1 and human 8-oxoguanine DNA glycosylase 1, OGG1) may play a key role in maintaining genome integrity and preventing cancer development.
For UADT cancer risk, associations were observed for the homozygous carriers of the variant alleles of MGMT L84F [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.32-4.20], MGMT 171C > T (OR 2.24, 95% CI 1.20-4.17) and OGG1S326C (OR 2.07, 95% CI 1.15-3.73) whilst three variants were associated with a protective effect (XPA 23G > A, P for trend 0.022, APEX Q51H, P for trend 0.036, CHEK2 intron 9-200T > C, P for trend 0.009).
In this study, we targeted mitochondrial DNA to enhance cancer chemotherapy by over-expressing a human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene in the mitochondria of human hepatoma cells.
In addition, we found no association between the hOGG1Ser326Cys polymorphism and cancer risk, MSI status, TNM stage or tumor location in colorectal cancer patients.
Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer in cohort settings, whereas altered levels of damage, repair or urinary excretion in case-control settings may be a consequence rather than the cause of the disease.
Moreover, the combination of smoking and low OGG activity was associated with a higher risk, suggesting a potential strategy for risk assessment and prevention of lung cancer, as well as other types of cancer.
The hOGG1 codon 326 genotypes were differently distributed between the oral cancer and control groups (p=0.0266) and the C allele of hOGG1 codon 326 was significantly (p=0.0046) more frequently found in cancer patients than in controls.