Molecular characterization of glutathione S-transferase, endothelial nitric oxide synthase and Vitamin D receptor genes in breast cancer cases

Enzymes of the Glutathione S-transferase system [GST] modulate the effects of exposure to several cytotoxic and genotoxic agents. Nitric oxide [NO] is constitutively synthesized in the endothelium by endothelial nitric oxide synthase [eNOS] and acts as a pleiotropic regulator involved in carcinogenesis. Vitamin D levels may influence breast cancer development. The vitamin D receptor [VDR] is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. To check for the association of polymorphisms of GST, eNOS3 and VDR genes with the susceptibility and severity of breast cancer in Egyptian cases. This work included 100 cases with breast cancer and 100 healthy individuals. The mean age of cases was 48.31 +/- 11.40 years. They included 100 females. DNA was amplified using PCR-RFLP for detection of polymorphisms related to eNOS3 and VDR, also DNA was amplified using PCR-SSP for detection of polymorphisms related to GST and calculating the odds ratios and their 95% confidence intervals. Total cases showed high significant frequency of eNOS3[-786] CC [P<0.05, OR=18.58] genotypes, GSTT1 [null] [OR = 2.68; CI 95%=1.51-4.75; p=0.001]. These were considered risk genotypes for disease susceptibility. On the other hand, total cases showed low significant frequency with homozygosity for eNOS3[-786] TT [P=0.01] and the GSTT1 gene was present in 42.0% of the cancers and in 66.0% of controls [OR = 0.37; CI 95%= 0.21-0.66; p=0.001]. These may be considered low risk genotypes. No significant difference in frequencies of null and present genotypes of GSTM1 and VDR FOKI in total cases compared to controls. Polymorphisms related to eNOS3[-786], GSTT1 and VDR FOKI genes may be considered genetic markers for BC among Egyptian cases. This may have potential impact on family counselling as well as future management plans

MTHFR gene polymorphisms as risk factors for colorectal cancer among Egyptian patients

Polymorphisms in methylenetetrahydrofolate reductase [MTHFR], such as MTHFR C677T and A1298C, are associated with several cancers. This study aimed to evaluate the effects of MTHFR polymorphisms on colorectal cancer risk in a population from damitta Egypt. This hospital-based case-control study was conducted during 2008-2010; 64 colon cancer cases and 90 controls were enrolled. Information was collected and blood samples were obtained for assay of MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-single strand conformation polymorphism [PCR-SSCP] and PCR-restriction fragment length polymorphism [PCR-RFLP] techniques. Associations between variables of interest and colorectal cancer were assessed using conditional logistic regression. Increased risk of colorectal cancer was associated with the MTHFR C677 TT genotype of C677T polymorphism [OR [adj] = 24.0; 95% CI: 1.34-429.1; P value for interaction = 0.001]. The 1298AC genotype and C allele was associated with a statistically significant lower risk among subjects [OR, 3.85; 95% CI, 1.78-8.33; P value for interaction=.0005 and OR, 1.88; 95% CI, 1.16-3.059 P value for interaction=0.01], respectively. MTHFR 1298 AA genotype and A allele was found to be associated with a significantly decreased risk for colorectal cancer [OR = 0.25, 95% CI 0.11-0.52; P value for interaction= 0.0005 and OR = 0.52, 95% CI 0.32-0.85 P value for interaction= 0.01and], respectively. There was no clear relation between colorectal adenomas and those with the 1298 CC genotype. The combined CC, AA [corrected] genotypes and the CT+AA [corrected] genotypes and the TT+ AC were associated with a statistically significant lower risk for developing colorectal cancer [P value for interaction= 0.03, 0.02, 0.001], respectively. The findings suggest an interaction between the MTHFR genotype and colorectal adenomas among Egyptian patients

IL-10 Implications in Psoriasis

Interleukin [IL]-10 is a pluripotent cytokine with effects on numerous cell populations, in particular circulating and resident immune cells as well as epithelial cells. With its potent immunoregulatory capacities, its main biological function seems to be the limitation and termination of inflammatory responses. Hence, its low level expression found in psoriasis may have pathophysiological relevance to this immune disease. Remarkably, the induction of IL-10 expression was found by conventional antipsoriatic therapies, supporting the hypothesis that it may be a key cytokine in psoriasis. Furthermore, the first use in clinical trials in patients with established psoriasis showed that it had moderate antipsoriatic effects and was well tolerated. Moreover, long-term application in psoriatic patients in remission showed that it decreases the incidence of relapse and prolongs the disease free interval. The IL-10 antipsoriatic activity is suggested to be due to the effects on different cell populations, including antigen presenting cells and T-cells [type 1/type 2 balance shift], but not through direct effects on keratinocytes. In conclusion, IL-10 seems to have major clinical and therapeutic implications in psoriasis. Further multicenter, placebo-controlled, double blind trials are required to be an established antipsoriatic therapy. We can come to the conclusion that IL-10 genetic polymorphism and expression is potentially a key immune marker in psoriasis