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

Authors' Affiliations: Departments of ¹ Biostatistics and Research Epidemiology and ² Surgical Pathology, Henry Ford Health System; ³ Population Studies and Prevention Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan; Departments of ⁴ Epidemiology and ⁵ Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York; and ⁶ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio

Requests for reprints: Benjamin A. Rybicki, Department of Biostatistics and Research Epidemiology, Henry Ford Health System, 1 Ford Place, 3E, Detroit, MI 48202. Phone: 313-874-6360; Fax: 313-874-6730; E-mail: brybick1{at}hfhs.org.

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.