الفهرس 
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Abstract
Oesophageal cancer is one of the most common diseases in the world, and prevention of this type of cancer requires a better understanding of the risk factors of oesophageal cancer. Alterations of cell cycle-regulated genes play an important role in the process of carcinogenesis, and some of them are thought to be prognostic factors in oesophageal cancer. In this study, the samples were collected from 50 patients suffering from oesophageal cancer, aged between 31 to 79 years with the average age 56.44 years. The samples were used for molecular biology and biochemical investigations as the following; 30 samples were paraffin embedded tissue, and 20 samples were fresh biopsy tissue. The fresh biopsy tissues were kept under low freezing temperature (-80 °C). Besides, 20 normal samples were taken from safety margins of the tumour tissues. Furthermore, blood samples were taken from 25 oesophageal cancer patients and from 20 healthy volunteers as control. These samples were used to identify the probable changes in the frequency of exons 1 and 2 in p16 gene (tumour suppressor gene), and to identify some biochemical changes, which are related to cancer diseases.
It was found that there are significant correlations between sex, age and incidence of oesophageal cancer. The rate of oesophageal cancer in Egyptians ranged between 50 to 69 years was higher than the rate of patients less than 50 years and accordingly, the cancer incidence increases with increasing age, and also increases in males than in females.
Single-strand conformation polymorphism (SSCP) analysis was performed on all of the positive polymerase chain reaction (PCR) samples. 5 cases from 30 successful PCR cases representing 17% (5/30), from 5 samples revealed abnormal SSCP-band shift, the mutations were indicated in 2 samples only by automated DNA sequencer, which represent about 6 % (2/30) of the successful PCR reactions. No mutations were detected in p16 exon 1, while there were 2/2 (100 %) in p16 exon 2. The 2 observed mutations occurred in 2 different patients, A----G (n=1) and G----A (n=1) which represent 2 transitions. These mutations lead to amino acid change (synonymous mutation). However, the 20 control tissue samples showed no mutations. Methylation of the p16 gene was detected in 28 (56%) primary tumours and 4 (20%) of the 20 safety margin tissues. There was a significant difference in methylation between the tissues of the primary tumours and safety margin tissues. Methylated p16 was found in 12/25 (48%) of the blood of oesophageal cancer patients and 4/20 (20%) of the blood of healthy controls. In the same direction, the mean incidence of methylated p16 was 52 copies/ml (range 0 ─ 320 copies/ml) in the leucocytes of oesophageal cancer patients and 8 copies/ml (range 0 ─ 60 copies /ml) in the leucocytes of healthy controls.
The superoxide dismutase (SOD) levels were significantly decreased in all tissues and blood groups than in the control group. But between cancer groups (grade I, grade II, grade III, cancer patients treated with radiation, cancer with smoking, and cancer with smoking and treated with radiation group) there were no significant differences.
The glutathione reductase (GR) levels were significantly increased in all tissues and blood cancer groups than in the control group. But between cancer groups (grade I, grade II, grade III, cancer patients treated with radiation, cancer with smoking, and cancer with smoking and treated with radiation group) there were no significant differences.
The lipid peroxidation levels in tissues and blood were significantly increased in all oesophageal cancer groups if compared with the control group.
Total protein in the blood recorded no significant changes in all cancer groups if compared with the control, but in tissue groups the total protein levels were significantly decreased in all oesophageal cancer groups if compared with the control group.
Conclusion:
The present study shows that aberrant hypermethylation in p16 gene in leucocytes of oesophageal cancer patients can be used as biomarker for this cancer. It also shows the relation between antioxidant enzymes activity, MDA content, mutations and the incidence of oesophageal cancer among Egyptians. All these parameters need more studies on a large scale. These studies must include the effect of nutrition, social habits, and other genes on incidence of oesophageal cancer.