Sexual dimorphism in cancer incidence and outcome is widespread. Understanding the underlying mechanisms is fundamental to improve cancer prevention and clinical management. Sex disparities are particularly striking in kidney cancer: across diverse populations, men consistently show unexplained 2-fold increased incidence and worse prognosis. We have characterized genome-wide expression and regulatory networks of 609 renal tumors and 256 non-tumor renal tissues. Normal kidney displayed sex-specific transcriptional signatures, including higher expression of X-linked tumor suppressor genes in women. Sex-dependent genotype–phenotype associations unraveled women-specific immune regulation. Sex differences were markedly expanded in tumors, with male-biased expression of key genes implicated in metabolism, non-malignant diseases with male predominance and carcinogenesis, including markers of tumor infiltrating leukocytes. Analysis of sex-dependent RCC progression and survival uncovered prognostic markers involved in immune response and oxygen homeostasis. In summary, human kidney tissues display remarkable sexual dimorphism at the molecular level. Sex-specific transcriptional signatures further shape renal cancer, with relevance for clinical management.

Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89–8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19–2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56–11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55–8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05–44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene–gene interactions in human susceptibility to this cancer.

In recent years, the progress of science and medicine greatly has influenced human life span and health. However, lifestyle habits, like physical activity, smoking cessation, moderate alcohol consumption, diet, and maintaining a normal body weight represent measures that greatly reduce the risk of various diseases. The type of diet is very important for disease development. Numerous epidemiological clinical data confirm that longevity is linked to predominantly plant-based diets and it is related to a long life; whereas the western diet, rich in red meat and fats, increases the risk of oxidative stress and thus the risk of developing various diseases and pre-aging. This review is focused on the bioavailability of polyphenols and the use of polyphenols for the prevention of prostate diseases. Special focus in this paper is placed on the isoflavonoids and flavan-3-ols, subgroups of polyphenols, and their protective effects against the development of prostate diseases.

Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis.

Background: Penile cancer (PC) is a highly aggressive disease, with a significant tendency for lymphatic spreading and subsequent development of distant metastases. The mutilating nature of PC surgical treatment has profound implications on the patient’s body integrity and self-image, sexual life and intimacy, voiding and mental health. The aim of our study was to comprehensively evaluate PC patients’ post-treatment quality of life (QoL), sexual activity, self-esteem, fatigue and fear of disease recurrence. (2) Methods: A cross-sectional study was conducted at the Clinic of Urology, University Clinical Centre of Serbia, and included 31 PC patients. Data were collected by means of a questionnaire. (3) Results: The average score on the Global health status scale was 67.2 out of 100 (ranging from 16.7 to 100), and the SD was 22.5. Hierarchical linear regression analysis showed that demographic characteristics, Hospital Anxiety and Depression scale (HADS) anxiety and depression scores, total Multidimensional Fatigue Inventory, Fear of cancer recurrence and Rosenberg scores and erectile function score explained a total of 78.2% of the variance in the global health status/QoL scale of PC patients. (4) Conclusions: Efforts should be made not only to increase the survival of PC patients after surgical treatment but also to enable the best possible level of QoL in the post-operative period.