Objectives: We undertook the present study to investigate the possible alteration of oxidant/antioxidant status in the circulation of patients with prostate cancer and benign prostatic hyperplasia.Design and methods: Thiobarbituric acid reactive substances (TBARS), the enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and copper (Cu) and zinc (Zn) levels were estimated in the erythrocytes of 25 non-metastatic prostate cancer patients, 36 benign prostatic hyperplasia (BPH) patients and 24 age-and sex-matched healthy subjects (controls).Results: TBARS concentrations were significantly increased, while erythrocyte GPX and SOD activities were significantly decreased in the prostate cancer group versus controls (P b 0.001) and BPH group (P b 0.05). Zn levels were lowered in prostate cancer patients versus controls (P b 0.01) with no significant changes between BPH and cancer groups. Similarly, lipid peroxidation was increased (P b 0.05) with decreased SOD activity and Zn level (P b 0.05) in BPH versus controls.Conclusion: These results reveal an alteration in the lipid peroxidation index, with concomitant changes in the antioxidant defense system in prostate cancer patients compared to BPH patients. We hypothesize that an altered prooxidant-antioxidant balance may lead to an increase in oxidative damage and consequently may play an important role in prostate carcinogenesis.

Objectives: The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Design and methods: 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO 2 − /NO 3 − ), cGMP and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels.Results: A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO 2 − /NO 3 − and cGMP levels versus controls and BPH groups in both studied samples.Conclusions: This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

Graphical Abstract Highlights d Biallelic germline NTHL1 mutations predispose to a multitumor syndrome d Biallelic germline NTHL1 mutation carriers are at risk for breast cancer d Tumors from NTHL1-deficient patients reveal a cross-cancer NTHL1-associated signature d Mutational signature analyses can assist to identify germline DNA repair defects

BackgroundAlthough age-related loss of chromosome Y (LOY) in normal hematopoietic cells is a well-known phenomenon, the phenotypic consequences of LOY have been elusive. However, LOY has been found in association with smoking, shorter survival and higher risk of cancer. It was suggested that LOY in blood cells could become a predictive biomarker of male carcinogenesis.Aims, Methods & FindingsTo investigate the association of LOY in blood cells with the risk for development of colorectal (CC) and prostate cancers (PC), we have analyzed DNA samples from peripheral blood of 101 CC male patients (mean age 60.5±11.9 yrs), 70 PC patients (mean age 68.8±8.0 yrs) and 93 healthy control males (mean age 65.8±16.6 yrs). The methodology included co-amplification of homologous sequences on chromosome Y and other chromosomes using multiplex quantitative fluorescent (QF) PCR followed by automatic detection and analysis on ABI 3500 Genetic Analyzer. The mean Y/X ratio was significantly lower in the whole group of cancer patients (0.907±0.12; p = 1.17x10-9) in comparison to the controls (1.015±0.15), as well as in CC (0.884±0.15; p = 3.76x10-9) and PC patients (0.941±0.06; p = 0.00012), when analyzed separately. Multivariate logistic regression analysis adjusting for LOY and age showed that LOY is a more significant predictor of cancer presence than age, and that age probably does not contribute to the increased number of subjects with detectable LOY in cancer patients cohort.ConclusionIn conclusion, our results support the recent findings of association of LOY in blood cells with carcinogenesis in males.

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20-0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.