DNA damage levels in prostate cancer cases and controls

Abstract

This study used the alkaline Comet assay to evaluate whether basal or H2O2-induced DNA damage is associated with prostate cancer (CaP) risk. Using lymphocyte samples from 158 CaP cases and 128 controls, collected in an ongoing case-control study, our results showed that basal DNA damage did not differ between cases and controls. However, the H2O2-induced DNA damage level was significantly higher in incident cases (mean +/- SD; 6.61 +/- 4.43, n = 102) than controls (5.30 +/- 3.60, n = 128) or prevalent cases (4.47 +/- 3.19; n = 56). Incident cases with a positive smoking history had significantly higher H2O2-induced DNA damage than never-smokers (7.57 +/- 4.82 versus 4.52 +/- 2.40; P < 0.001). Above-median H2O2-induced DNA damage was associated with a 1.61-fold increase in CaP risk [95% confidence interval (CI) = 0.92-2.81], after adjustment for age, race, benign prostatic hyperplasia (BPH), smoking history and family history (FH). Using the lowest quartile of H2O2-induced DNA damage as the referent group, the adjusted ORs for the 25th, 50th and 75th quartiles were 0.90 (95% CI = 0.39-2.05), 1.06 (95% CI = 0.48-2.35) and 2.05 (95% CI = 0.96-4.37), respectively (P = 0.046, test for linear trend). The association between CaP and DNA damage was modified by age, smoking history, family history and body mass index. Our results suggest that DNA damage may be associated with CaP risk. However, larger case-control and follow-up studies are warranted to further evaluate the potential application of the alkaline Comet assay in CaP risk assessment and prevention.

Functional Variant of Manganese Superoxide Dismutase (SOD2 V16A) Polymorphism Is Associated with Prostate Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Study

“…Thus, it is hypothesized that the higher activity (Ala) variant suppresses prostate carcinogenesis; however, our results and previous association studies on prostate cancer contradict this hypothesis (17,18). (34) and in induction of genes for prostate carcinogenesis (33,35). Thus, the SOD2 Ala allele might increase the risk of prostate cancer by producing excessive H 2 O 2 .…”

Polymorphisms in Oxidative Stress–Related Genes Are Not Associated with Prostate Cancer Risk in Heavy Smokers

“…Previous studies found that patients with prostate cancer had lower expression of antioxidant enzymes (i.e., MnSOD, CAT, and GPX1) than men with benign disease or healthy controls (2)(3)(4)(5) and noted that DNA damage in prostate cancer tissue from aging males seems to be the result of oxidative damage induced by hydroxyl radicals (18,19). Recently, Lockett et al (20) found that hydrogen peroxideinduced DNA damage in lymphocytes was associated with a 1.6-fold increase in prostate cancer risk, and relationships seemed to be modified by exogenous sources of ROS, such as smoking history and BMI.…”

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

“…Although our results are generalizable to prostate cancer patients that undergo prostatectomy as their primary form of treatment, we cannot necessarily infer that elevated PAH-DNA adduct levels affect disease progression the same way in prostate cancer patients that receive other forms of treatment such as hormone or radiation therapy. A missing aspect of the analyses in the present study that would be of interest in terms of prevention is the source of PAH exposure(s) that lead to high adduct levels and biological modifiers that influence adduct formation and prostate cancer risk, such as inherited capacities for high metabolism of PAH (8,15) or poor DNA repair capacity (50,51). Although these risk factors for PAH-DNA adducts have meaning in terms of understanding the underlying reasons for interindividual variation in PAH-DNA adduct levels, because they are antecedent factors in a causal pathway they provide no further understanding of the role of adducts in BCR (52), which was the central point of this study.…”