CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Altered expression of WFS1 and NOTCH2 genes associated with diabetic nephropathy in T2DM patients.

AIM: The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identification and management of its complications, especially diabetic nephropathy (DN), have spotted the light on genetic factors that increase risk of T2DM and its related nephropathy. The present study aimed at investigating expression of (KCNJ11, ABCC8, JAZF1, WFS1, PPARG, NOTCH2 and EXOSC4) genes in peripheral blood of T2DM patients. METHOD: The study included 30 non-complicated T2DM patients, 30 patients with DN and 40 healthy controls. Quantitative Real Time PCR Array was used to study gene expression. RESULTS: NOTCH2 showed higher expression while KCNJ11, JAZF1, WFS1 and PPARG genes showed lower expression in DN patients compared to non-complicated patients. KCNJ11, JAZF1, WFS1, PPARG, and EXOSC4 expression showed significant negative correlation with microalbumin, while NOTCH2 expression was significantly positively correlated with microalbumin. AS regard HbA1c and studied genes expression, there was significant negative correlation between WFS1 expression and HbA1c, while NOTCH2, KCNJ11, JAZF1, PPARG, EXOSC4 expression didn't show significant correlation with HbA1c. Risk ratio of studied genes expression showed that WFS1 and NOTCH2 had highest risk ratio (30) and highest sensitivity and specificity, in relation to DN and they were the best predictors in the group of studied genes at cut off value of ≤0.861 for WFS1 and ≥0.678 for NOTCH2. CONCLUSION: Altered expression of WFS1 and NOTCH2 genes may play a role in pathogenesis and development of DN in patients with T2DM. These results may contribute in early identification and management of DN.

Serum levels of interleukin-8, tumor necrosis factor-α and γ-interferon in Egyptian psoriatic patients and correlation with disease severity.

Psoriatic plaques have been shown to contain increased levels of pro-inflammatory cytokines. Also, serum levels of several cytokines have been reported elevated in psoriatic patients. It is postulated that changes in cytokine production both locally and systemically could be useful in monitoring disease activity. The aim of this study was to evaluate serum cytokine profile of interleukin (IL)-8, γ-interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) in Egyptian psoriatic patients by enzyme-linked immunosorbent assay (ELISA) technique and to correlate these levels with disease severity. We analyzed serum samples from 60 Egyptian patients (31 females and 29 males) with a mean age of 40.2 ± 17.4 years with active psoriasis, and 21 healthy volunteers for major T-helper type 1 cytokines using the ELISA technique. The disease severity, including erythema, induration and scales, was assessed by Psoriasis Area and Severity Index (PASI) score. TNF-α and IFN-γ were markedly elevated in all sera from psoriatic patients. TNF-α was found a more efficient predictor for disease severity than IL-8 and IFN-γ using three receiver-operator curves with accuracy. IL-8 was also moderately elevated and correlated with the age of patients (r = 0.28). We have obtained evidence that TNF-α in our study was found to be more useful than the other two tested cytokines, IL-8 and IFN-γ as a follow-up marker for monitoring disease severity in Egyptian psoriatic patients. A positive correlation between lL-8 and the age of the patients was also noted.