Polycyclic aromatic hydrocarbon--DNA adducts in prostate and biochemical recurrence after prostatectomy.
OBJECTIVE
DNA adduct levels may be influenced by metabolic activity, DNA repair capabilities, and genomic integrity, all of which play a role in cancer progression.


METHODS
To determine if elevated DNA adducts are a marker for prostate cancer progression, we measured polycyclic aromatic hydrocarbon-DNA adducts by immunohistochemistry in prostate cells of 368 surgical prostate cancer patients treated at the Henry Ford Hospital in Detroit, Michigan, between September 1999 and July 2004. Patients were followed up to 5 years after surgery with relative risk for biochemical recurrence (BCR) estimated with a Cox proportional hazards model that adjusted for standard clinical risk factors.


RESULTS
At 1 year of follow-up, patients with adduct levels above the median in tumor cells [hazard ratio (HR), 2.40; 95% confidence interval (95% CI), 1.10-5.27] and nontumor cells (HR, 3.22; 95% CI, 1.40-7.39) had significant increased risk of BCR, but these HRs decreased to 1.12 (95% CI, 0.68-1.83) and 1.46 (95% CI, 0.89-2.41) in tumor and nontumor cells at 5 years postsurgery. When we restricted our analysis to patients with advanced-stage (III+) disease, those with high adduct levels in either tumor (53.5% versus 30.2%; P = 0.07) or nontumor (55.2% versus 28.6%; P = 0.02) cells had BCR rates almost 2-fold higher. In race-stratified analyses, the greatest risk of BCR associated with high adduct levels (in nontumor cells) was for African American patients younger than 60 years old (HR, 3.79; 95% CI, 1.01-14.30).


CONCLUSIONS
High polycyclic aromatic hydrocarbon-DNA adduct levels in nontumor prostate cells are most strongly associated with BCR between 1 and 2 years after surgery and in patient subsets defined by younger age, advanced tumor stage, and African American race.
Rybicki
Benjamin A
BA
Departments of Biostatistics and Research Epidemiology and Surgical Pathology, Henry Ford Health System, Detroit, Michigan 48202, USA. brybick1@hfhs.org
Neslund-Dudas
Christine
C
Bock
Cathryn H
CH
Rundle
Andrew
A
Savera
Adnan T
AT
Yang
James J
JJ
Nock
Nora L
NL
Tang
Deliang
D
D000368:Aged; D014408:Biomarkers, Tumor; D018736:DNA Adducts / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D012372:ROC Curve; D012008:Recurrence
D014408:Biomarkers, Tumor; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct