ABSTRACT
BACKGROUND: Prostate cancer (PCa) displays a strong familiarity component and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions and ultimately carcinogenesis. The enzyme glycine-N-methyltransferase (GNMT) contributes to S-adenosylmethionine level regulation and, by affecting DNA methylation, influences gene expression. The genotype and allele distribution of single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular endothelial growth factor (VEGF), interleukin (IL)-10, IL-1ß, alpha-1-antichymotrypsin (ACT) and GNMT genes, the level of global DNA methylation and the influence of GNMT SNP upon DNA methylation in a PCa case-control study have been investigated. METHODS: SNPs of VEGF (rs699947), ACT (rs1884082), IL-1ß (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or by real-time PCR methods. DNA methylation was assessed by an ELISA assay. RESULTS: Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T allele were higher in PCa. The concomitant presence of the AA genotype of VEGF, the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest level of DNA methylation. CONCLUSIONS: SNPs in VEGF, IL-10 and GNMT genes might have a synergistic role in the development of PCa. The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa.
Subject(s)
DNA Methylation/genetics , Genetic Predisposition to Disease/genetics , Inflammation/genetics , Prostatic Neoplasms/genetics , Aged , Alleles , Genotype , Glycine N-Methyltransferase/genetics , Humans , Inflammation/pathology , Interleukin-10/genetics , Interleukin-1beta/genetics , Male , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Prostatic Neoplasms/pathology , Vascular Endothelial Growth Factor A/genetics , alpha 1-Antichymotrypsin/geneticsABSTRACT
The aim of this study is to compare different tools for evaluating prostate-specific antigen (PSA) increase or decrease, such as PSA velocity and PSA slope. This study was conducted on 312 male patients evaluated with transrectal ultrasound-guided biopsy of prostate with six or more cores. Patients with at least three consecutive PSA measurements in at least 18 months entered the study. Prostate-specific antigen slope was estimated by the slope of the least-square regression line fit to PSA versus time in years; PSA velocity was calculated with 3 or more PSA arrays. Median age was 66 years (range 45-86). Overall 67 patients were affected by primary prostate cancer, 245 were controls without prostate cancer. Prostate-specific antigen slope and PSA velocity were significantly higher in patients with prostate cancer than in controls. At the ROC analysis, PSA slope evidenced better results than PSA velocity (area under the curve (AUC) 0.743 for PSA slope; AUC 0.663 for PSA velocity; P=0.037). At PSA slope (calculated with the least-square fit) equal to zero, the sensitivity resulted as being 94% with a specificity of 38.8%. In conclusion prostate-specific antigen slope calculated with three or more PSA assays permits longitudinal evaluation of PSA for prostate diagnosis. Prostate-specific antigen slope improves both sensitivity and specificity in prostate cancer diagnosis, compared with PSA velocity.
Subject(s)
Biomarkers, Tumor/analysis , Neoplasm Invasiveness/pathology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Area Under Curve , Case-Control Studies , Cohort Studies , Endosonography/methods , Humans , Male , Middle Aged , Monitoring, Physiologic , Neoplasm Staging , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/diagnostic imaging , ROC Curve , Reproducibility of Results , Risk Assessment , Sensitivity and Specificity , Statistics, NonparametricABSTRACT
We retrospectively reviewed the outcome of 28 prostate cancer patients with ureteral obstruction treated by percutaneous nephrostomy. The over-all survival was 60% at 1 year and 32% at 2 years. The 1 and 2 years survival rates of 13 patients with no prior hormonal therapy were 70 and 45%, respectively, while those of patients who had previously received hormonal therapy were 46 and 17% respectively. Of 10 patients who had severe renal failure before percutaneous nephrostomy (serum creatinine greater than or equal to 7 mg per dl), 8 had an adequate return of renal function (serum creatinine less than 3 mg pe dl) after drainage and 55% survived more than 1 year, cutaneous nephrostomy is safe and effective in relieving ureteral obstruction and reasonable survival can be achieved even in patient with renal failure. Percutaneous nephrostomy should be considered strongly in these patients.
