Polycyclic Aromatic Hydrocarbon-DNA Adducts in Prostate Cancer

Abstract

The formation of DNA adducts can lead to DNA replication errors and the potential for carcinogenesis. DNA adducts have been detected in prostate cells, but the distribution of adducts with respect to prostate cancer risk factors and histology is unknown. In a study of 130 Caucasian (n ‫؍‬ 61) and African-American (n ‫؍‬ 69) men with prostate cancer who underwent radical prostatectomy, we quantified polycyclic aromatic hydrocarbon (PAH)-DNA adducts in prostate tumor and adjacent nontumor cells by immunohistochemistry. A strong correlation between paired adduct levels in the two cell types was observed (r ‫؍‬ 0.56; P < 0.0001); however, nontumor cells had a significantly higher level of adducts compared with tumor (0.30 absorbance units ؎ 0.05 versus 0.17 absorbance units ؎ 0.04; P < 0.0001). Variables significantly associated with PAH-DNA adduct levels in tumor cells included primary Gleason grade, tumor volume, and log-transformed prostate-specific antigen (PSA) at time of diagnosis. Tumors with a primary Gleason grade of 5 had significantly lower PAH-DNA adduct levels than tumor cells with a primary Gleason grade of 3 or 4 (P < 0.0001 for both). Tumors that involved 10% or less of the prostate gland had significantly higher PAH-DNA adduct levels than tumors that involved 15 to 20% of the prostate gland (P ‫؍‬ 0.004). PSA levels were inversely associated with PAH-DNA adduct levels in tumor cells (P ‫؍‬ 0.009). A similar, albeit less significant, inverse association was observed between PSA and PAH-DNA adduct levels in nontumor cells (P ‫؍‬ 0.07). Interestingly, increasing primary Gleason grade was associated with increasing PAH-DNA adduct levels in adjacent nontumor cells (P ‫؍‬ 0.008). Our results show that PAH-DNA adducts are present in the prostate but vary with regard to cellular histology. In prostate tumor cells, decreased cellular differentiation and increased tumor proliferation may reduce PAH-DNA adduct levels.

Investigation of NQO1 genetic polymorphism, NQO1 gene expression and PAH-DNA adducts in ESCC. A case-control study from Iran

“…Contrary to our findings on ESCC, some studies on the role of PAHs in prostatic cancer do not strongly support the role of PAHs in prostatic cancer risk (Rybicki et al, 2004;John et al, 2009).…”

Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile105Val polymorphism

“…Associations between prostate cancer and specific occupational PAH exposure sources have also been reported [14,15]. In addition, we have recently shown that PAH-DNA adducts form in the prostate, and vary in level according to cellular histology [16].…”

“…Even for three-way interactions, assuming the third factor was evenly distributed across cases, our sample afforded the ability to detect iOR for the third factor of 2.1 or greater with 80 percent statistical power. Our study lacked a measure of biologically effective dose, but we have demonstrated in a previous study of a subset of cases drawn from this same study population that PAH-DNA adducts are detectable in the prostate epithelial cells of cases [16].…”

Associations between Smoking, Polymorphisms in Polycyclic Aromatic Hydrocarbon (PAH) Metabolism and Conjugation Genes and PAH-DNA Adducts in Prostate Tumors Differ by Race

“…The study design and population have been described elsewhere (13). Briefly, the study population was composed of men from a larger case (n = 637) and control (n = 244) study who were diagnosed with prostate cancer and underwent radical prostatectomy (n = 395; 62.0%) or transurethral resection (n = 5; 0.7%) for treatment within the Henry Ford Health System, a network of facilities comprising an 800-bed hospital in the City of Detroit, Michigan, three smaller hospitals in surrounding suburbs, and 31 medical clinics located throughout the Metropolitan Detroit area.…”

“…Furthermore, many prior studies have relied upon self-reported measures from a single source; however, PAH-DNA adducts serve as a biological marker of the effective PAH dose from all sources, particularly when quantified in the target tissue. We previously observed that PAH-DNA adducts are present in human prostate cancer cells and vary with tumor characteristics (13).…”