Genetic Variation of <i>hTERT</i>, Leukocyte Telomere Length and the Risk of Breast Cancer: A Case-Control Study in Egyptian Females

Background: hTERT is a key player in telomere biology and its activity is directly related to cell senescence and development of many health-related problems including cancer. Although previous studies investigated this association, the results greatly vary among populations. This study aimed to investigate the association of hTERT gene SNPs and the risk of breast cancer (BC) in Egyptian females and their impact on telomere length (TL). Methods: 218 BC patients and 178 age-matched healthy females were genotyped for hTERT variants rs2736098G > A, rs2735940C > T using PCR-RFLP and for MNS16A tandem repeat using PCR to determine their association with breast cancer risk. Telomere length was measured using qPCR. Results: hTERT rs2736098G > A results indicated that both AG and GG genotypes and G allele were associated with an increased risk of BC. The rs2735940 TT genotype was significantly associated with BC risk, however, the MNS16A tandem repeat region polymorphism didn’t show any correlation with the risk of developing BC. TL showed a significant reduction in BC patients with age 40 years compared with controls. However, it didn’t show a significant difference above the age of 40 years. Conclusions: hTERT rs2736098 and rs27365940, not MNS16A may be associated with an increased risk of developing BC in Egyptian females. Also, telomere length can be a promising screening marker of BC especially in young population.

The Role of Serum Trace Elements and Oxidative Stress in Egyptian Breast Cancer Patients

Background: Oxidative stress is considered to be involved in the pathophysiology of all cancers. Studies indicated that the levels of oxidative stress markers increased in breast cancer. Trace metals are essential to normal human homeostasis. When present in an abnormal expression, they contribute in many pathological processes. Some trace metals are claimed to be carcinogenic and capable of inducing a toxic effect through the formation of free radicles and acting as cofactors in the oxidative damage of biological macromolecules and DNA. Objective: Our aim was to investigate the serum levels of some trace elements (Copper, Zinc and Cadmium), the total oxidative and anti-oxidative capacity (TOC and TAC) in patients with breast cancer in comparison to patients with benign breast tumours. Patients and Methods: The present study included 65 females. The participates were divided into 2 main groups: control group which consisted of 20 apparently healthy female;the patient groups which divided into 3 groups: group B included 15 patients with benign breast tumours, group N consisted of 15 newly diagnosed breast cancer patients and group M included 15 patients with metastatic breast cancer. Results: The mean serum levels of Copper, Zinc, and Cadmium were significantly higher in the three patients groups (B, N and M) than the control group. Similarly, serum uric acid (UA) and (TAC) levels showed significant higher level in both breast cancer groups as compared to the benign group. However TOC levels showed only significantly higher level in metastatic group. Conclusions: The present study suggested elevated TAC, UA and TOC in breast cancer patients. The increased levels of trace elements could lead to formation of free radicals or other reactive oxygen species. The serum profile of these trace metals may be helpful in predicting prognosis of breast cancer.

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.

Aberrant Vimentin Methylation Is Characteristic of Breast Cancer

Background: Epigenetic mechanisms including DNA methylation are key regulators of gene activity and may play key roles in carcinogenesis through cumulative activation and inactivation of oncogenes, tumor suppressor genes, and other genes. Increased vimentin gene expression has been reported in various tumor cell lines and tissues including breast cancer. In addition, methylation of the vimentin gene was described as a marker in several malignant tumors. Objective: The aim of this study is to determine the existence of a potential relationship between the methylation state of the vimentin gene and its prognostic value in breast cancer patients and its correlation with vimentin protein expression in the serum. Patients and Methods: The methylation status of the vimentin gene was examined in primary infiltrating ductaltumors and the surrounding normal tissues derived from 50 breast cancer patients enrolled for either modified radical mastectomy or conservative breast surgery using quantitative methylation-specific polymerase chain reaction (qMSP), serum vimentin levels were determined using ELISA, and the correlation between the methylation status and the clinicopathological findings was evaluated. Results: Out of 50 breast cancer patients, 18 (36%) exhibited positive methylation of vimentin gene while 32 (64%) exhibited negative vimentin genemethylation in their tumors. Subsequently clinicopathological data were correlated with the vimentin genemethylation score. A significant association was found between negative vimentin methylation, and both serum vimentin protein level (p 0.001) and the triple negative breast cancer subtype (TNBCs) (p = 0.004). Using receiver-operating characteristic (ROC) curve analysis, a cut off value of <0.49 was set for the negative vimentin methylation score to distinguish between early and late stage breast cancer, and the ROC curve showed an area under the curve (AUC) of 0.684 (p = 0.029). Conclusion: Our study showed that the vimentin gene is frequently hypomethylated in breast cancer tissues, and that negative methylation status is always associated with high serum vimentin protein expression levels. Also we reported a significant association between negative vimentin methylation and TNBC subtype which is known to have an aggressive clinical course. Taken together, these results might have important implications for the design of novel therapeutic interventions for breast cancer patients. However, further studies with larger sample size are needed to validate these observations.

Effect of Non-Delineated Normal Volumes in IMRT Treatment for Left Breast Cancer: A Treatment Planning Study

Introduction: Intensity Modulated Radiation Therapy (IMRT) planning dose calculation process depends on IMRT dose constraints. So, if there was any structure along the treatment beam path not delineated, it would not be taken into account during that calculation process. During IMRT routine practical work, it is noticed that there are some non-delineated normal tissue volumes that received un-aimed dose. Aim: The purpose of this study was to study the effect of unusually delineated normal volumes in IMRT treatment for left sided breast cancer. Method: Ten left sided breast cancer patients were planned with IMRT inverse planning system. The unusually delineated normal volumes were delineated and taken into account in IMRT dose constraints as an Organ at Risk. Doses received by that volume were compared in the two methods quantitatively from Dose Volume Histograms (DVHs) and qualitatively from (axial cuts). Results: The results showed that doses received by the unusually delineated volume when they were delineated and taken into account in IMRT dose constraints were significantly higher than when they were not. Conclusions: The results showed that for IMRT planning technique used for treating left-sided breast cancer, all of the normal tissues/structures that are closed to the treatment targets must be delineated and taken into account in the IMRT planning dose constraints.

Dose Validation of Physical Wedged Asymmetric Fields in Artiste Linear Accelerator

Aim: The purpose of this study was to make a comparison between measured and calculated physical wedge dose distributions using the superposition algorithm. Settings and Design: The accurate determination of absorbed dose is important radiotherapy because of the relatively steep sigmoidal dose response curves for both tumor control and normal-tissue damage. Materials and Methods: High-energy photons (6 and 10 MV) from Artiste Treatment System Linear Accelerator Machine, available at Alexandria Ayadi Al-Mostakbal Oncology Center, were used. Results and Discussion: The results showed that the difference between measured and calculated wedged isodose curves depends on field size, beam energy, and the angle of the used wedge. Conclusion: The results showed that the presence of a wedge alters the primary and scattered components generated by a linear accelerator and causes beam hardening in 6 and 10 MV. The beam hardening increased as the wedge angle increased.