8-Hydroxy-2'-deoxyguanosine (8-OH-dG) as a potential survival biomarker in patients with nonsmall-cell lung cancer.
BACKGROUND
8-Hydroxy-2'-deoxyguanosine (8-OH-dG) is 1 of the most abundant oxidative products of cellular DNA. Accumulation of impaired 8-OH-dG could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. Therefore, the effects of 8-OH-dG on survival in 99 resected nonsmall-cell lung cancer (NSCLC) patients was evaluated.


METHODS
The enzyme-linked immunosorbent assay was applied to measure the levels of 8-OH-dG in tumor DNA. The median levels of 8-OH-dG were 6.5 pmol/microg for all study subjects.


RESULTS
Patients with low levels of 8-OH-dG had significantly longer survival times compared with those with high levels of 8-OH-dG (log-rank test: P < .001). In Cox regression analysis, patients with high levels of 8-OH-dG had an over 3-fold increased hazard of death. In addition, a statistically significant correlation between levels of 8-OH-dG and age was noted (rho = 0.206, P = .048). Furthermore, we observed a genotype-phenotype modification between hOGG1 gene polymorphism (Ser326Cys) and levels of 8-OH-dG.


CONCLUSIONS
The results demonstrated that levels of 8-OH-dG could predict survival in resected NSCLC patients. It is postulated that an intact base excision repair mechanism may reduce the accumulation of oxidative DNA damage that is thought to contribute to the tumor's malignant potential and therefore the risk of death.
Shen
Jie
J
Department of Epidemiology, Division of Cancer Prevention and Population Science, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Deininger
Prescott
P
Hunt
Jay D
JD
Zhao
Hua
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003849:Deoxyguanosine