The DNA nanocage containing fluorescent QDs and Dox was successfully applied to the fluorometric detection of hOGG1, fluorescence imaging, and therapy of cancer cells, which has great promise in clinical application and treatment of cancer.
In fact, mice deficient in both OGG1 and MUTYH develop cancer in different organs at adult age, which points to the critical impact of 8-oxoG repair on genetic stability in mammals.
The CRC risk was higher in patients with the OGG1326Ser/Cys + Cys/Cys genotype (OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage III + IV cancer (OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype.
For that, we have used a series of 89 BRCA1 and BRCA2 mutation carriers, 74 BRCAX cases, 60 non-carrier controls and 23 lymphoblastoid cell lines (LCL) derived from BRCA1 mutation carriers and non-carriers.We have identified that this SNP is associated to a significant OGG1 transcriptional down regulation independently of the BRCA mutational status and that the variant may exert a synergistic effect together with BRCA1 or BRCA2 mutations on DNA damage and telomere shortening.These results suggest that this variant, could be associated to a higher cancer risk in BRCA1 mutation carriers, due to an OGG1 transcriptional down regulation and its effect on genome instability.
Overall, significant association was observed between OGG1Ser326Cys polymorphism and cancer risk in all genetic models except for heterozygote model (Cys/Cys + Cys/Ser vs Ser/Ser: OR 1.071, 95 % CI 1.019-1.125; Cys/Cys vs Cys/Ser + Ser/Ser: OR 1.159, 95 % CI 1.076-1.248; Cys/Cys vs Ser/Ser: OR 1.202, 95 % CI 1.105-1.308).
Patients with the variant 'G' allele of hOGG1rs1052133 had poor overall survival compared with those with the homozygous wild 'CC' genotype, especially in female patients, adenocarcinoma histology, early stage, light smokers and without family history of cancer.
In addition, decrease in tuberin expression resulted in a significant decrease in protein expression of OGG1 and increased in oxidative DNA damage, 8-oxodG in kidney tissues from patients with cancer or cancer+diabetes.
Our aim in this review is to compile published studies, including some controversial results on the association between the OGG1Ser326Cys polymorphism and the risk of cancer.
A frequent polymorphism in the human OGG1 gene, rs1052133, causes the substitution of serine by cysteine at amino acid 326 of the protein and has been associated with an altered risk for various types of cancer in some populations.
The human 8-oxoguanine DNA glycosylase (hOGG1) gene plays an important role in the repair of oxidatively damaged DNA base lesions and its functional single nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus contributes to cancer susceptibility.
The OGG1326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes were inversely associated with cancer risk (OR [95% CI] = 0.69 [0.50-0.95] and 1.35 [1.0-1.82], respectively).
The methylation level of BCAP31 and OGG1 showed significant association to survival, and these associations were validated in a larger patient cohort (The Cancer Genome Atlas).
This study suggests that the OGG1 polymorphism is not associated with the risk of development of CRC in the Kashmiri population in general but modulates the risk of cancer development in colon via interaction with many dietary factors.
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.