Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy

Abstract

Purpose: DNA adduct levels may be influenced by metabolic activity, DNA repair capabilities, and genomic integrity, all of which play a role in cancer progression. Experimental Design: 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.

Polymorphisms in glutathione S-transferase genes increase risk of prostate cancer biochemical recurrence differentially by ethnicity and disease severity

“…Furthermore, because we previously observed that PAH-DNA adducts in prostate cells were associated with an increased risk of prostate cancer BCR [21], we also performed all of the aforementioned analyses with additional adjustment for PAH-DNA adduct levels in a subset of patients with PAH-DNA adduct data also available ( N  = 368); and we observed no material differences in any of the results presented (data not shown).…”

Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon–DNA adduct levels in human prostate

“…One other group of investigators has examined PAH-DNA adduct formation in human prostate, and prostate tumour, using IHC [61,62]. Semi-quantitative values for intensity of nuclear staining were obtained upon examination of 100 cells in tumour and non-tumour areas from the same specimen, and the data showed that PAH-DNA adducts were higher in Caucasians who smoked, compared with non-smokers.…”

Prostate Tissue Metal Levels and Prostate Cancer Recurrence in Smokers

“…Formalin-fixed paraffin embedded (FFPE) prostate tissue of a subset of men who participated in the Gene-Environment Interaction in Prostate Cancer Study (GECAP) [22] and underwent prostatectomy for treatment of their cancer were selected for inclusion in this study. As part of the GECAP study, men completed a face-to-face interview to determine lifetime smoking history and occupational exposure to metals (Cd, Pb, and Zn), and completed a food frequency questionnaire.…”