8-Hydroxy-2′-deoxyguanosine (8-OH-dG) as a potential survival biomarker in patients with nonsmall-cell lung cancer

Abstract

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/μg 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. © 2006 American Cancer Society.