Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors.
Using statistical analyses of Fourier transform-IR spectra, we show that DNA of the histologically normal prostates of men 16-80 years old undergoes structural changes in the bases and backbone with increasing age. Of the older men (ages 55-80), 42% exhibited a DNA phenotype mimicking that of primary prostate tumors from a comparable age group. This cancer-like phenotype, which was not found in the younger men (ages 16-36), appears to arise from progressive age-related damage to DNA. The mean concentrations of 8-hydroxypurine lesions (e.g., 8-hydroxyguanine) were substantially higher for the older men than for the younger men. This finding suggests that the hydroxyl radical contributed to the structural changes that characterize the cancer-like phenotype. Strikingly, we were additionally able to discriminate between the DNA of primary prostate tumors and the DNA of primary prostate tumors from which distant metastases had been identified. Moreover, logistic regression analysis was able to predict the probability that a tumor had metastasized with approximately 90% sensitivity and specificity. Collectively, these findings are particularly promising for identifying men at risk for developing prostate cancer, as well as for the early determination of whether a primary tumor has progressed to the metastatic state. This is highly important because the prognosis of histologically similar prostate carcinomas varies, thus creating a need to predict which cancers are most likely metastatic.
Malins
Donald C
DC
Biochemical Oncology Program, Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA. dmalins@pnri.org
Johnson
Paul M
PM
Barker
Edward A
EA
Polissar
Nayak L
NL
Wheeler
Thomas M
TM
Anderson
Katie M
KM
D000293:Adolescent; D000328:Adult; D000368:Aged; D004247:DNA / Q000235:genetics*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017550:Spectroscopy, Fourier Transform Infrared
D004247:DNA