Abasic sites and survival in resected patients with non-small cell lung cancer.
Apurinic/apyrimidinic (AP or abasic) sites are common DNA lesions that arise from spontaneous depurination or by base excision repair (BER) of modified bases. Accumulation of impaired AP sites could lead to increased genomic instability that in turn could lead to a more malignant phenotypic behavior of tumors. We, therefore, evaluated the effects of AP sites on survival in resected non-small cell lung cancer (NSCLC) patients. Resected tumor specimens from 99 patients with NSCLC who underwent surgical resection were collected. The enzyme-linked immunosorbent assay was applied to measure the levels of AP sites in tumor DNA. The median number of AP sites per 10(5) nucleotides was 12.4 for all the study subjects. Patients with low levels of AP site had significantly longer survival time compared with ones with medium or high levels of AP site (log-rank test: P=0.015). In Cox regression analysis, patients with medium or high levels of AP sites had over twofold increased hazard of death. In addition, we found a statistically significant correlation between levels of AP sites and age (rho=0.560, P<0.001). The results of this study demonstrated that levels of AP sites could predict survival in resected NSCLC patients. We postulate that an intact BER mechanism may reduce the accumulation of oxidative DNA damage that are thought to contribute to the tumor's malignant potential and therefore the risk of death.
Zhao
Hua
H
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA. hzhao@tulane.edu
Shen
Jie
J
Deininger
Prescott
P
Hunt
Jay D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001080:Apurinic Acid / Q000032:analysis / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011119:Polynucleotides / Q000032:analysis / Q000378:metabolism; D016016:Proportional Hazards Models
D004273:DNA, Neoplasm; D011119:Polynucleotides; C001790:apyrimidinic acid; D001080:Apurinic Acid