رسائل دكتوراة
English
2021
The Assessment of c-myc (Myelocytoma) Gene Polymorphism in Patients with Bladder Cancer in Babylon Province
أحمد تركي عبيد , مفيد جليل عوض, هبة رشيد كاظم حمود بهية
كلية الطب-جامعة بابل · العراق
Bladder cancer (BC) is a complex disease associated with high morbidity and mortality rates if not treated optimally. Bladder cancer is the 10th most commonly diagnosed cancer in the world. The Myc gene is an important proto-oncogene transcriptional factor that encodes a nuclear phosphoprotein for intracellular processes. In the human genome, the Myc gene is located on band q24.21 of chromosome 8 and consists of three exons and two introns. Myc regulates a series of biological functions such as cell-cycle progression, nucleotide biosynthesis, energy metabolism, protein synthesis, and ribosome genesis. Such deregulation confers ample competitive advantages to the cell and contributes to the well-established role of Myc in a wide variety of cancers.
This study was designed to investigate the possible relation of Galectin-3 and oxidative stress markers like malondialdehyde and total glutathione levels with age, gender, and different stages and grades of bladder cancer, and to evaluate the risk of three candidate single nucleotide polymorphisms (SNPs) of the Myc gene (rs28933407 C>T, rs121918685 C>G, and rs9642880 G>T) on the development of bladder cancer in Babylon province.
To achieve these aims, the present study included 200 subjects. The first group included 100 patients with bladder cancer. The second group included 100 apparently healthy individuals, which served as the control group. Patient groups were divided into two subgroups: 46 patients with non-muscle-invasive bladder cancer and 54 patients with muscle-invasive bladder cancer. Galectin-3 concentration, malondialdehyde, and total glutathione were determined by enzyme-linked immunosorbent assay (ELISA). DNA was extracted from blood and genotyped for the first two SNPs (rs28933407 C>T and rs121918685 C>G) by conventional PCR and direct sequencing, while the rs9642880 G>T SNP was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Results were evaluated by various statistical analyses.
Galectin-3 concentration was increased significantly (p<0.05) in bladder cancer individuals (compared to the control group), suggesting that these levels correlate with the anti-apoptotic activity of Gal-3 as a possible cause of carcinogenesis. There were significant variations in the levels of malondialdehyde and total glutathione in the serum of non-muscle-invasive bladder cancer compared to muscle-invasive bladder cancer, as well as in patients with high-grade transitional cell carcinoma compared with low‑grade tumors and papillary urothelial neoplasm of low malignant potential.
On the other hand, all genotypes of SNPs studied in this research did not show any significant association (p>0.05) with bladder cancer. The present study concluded that bladder cancer patients in Babylon province have higher serum levels of Galectin-3 compared to normal subjects, and this level elevates more as the cancer progresses to advanced stages. Moreover, increased free radical generation with impairment of antioxidants plays an important role in the pathogenesis of bladder cancer. Finally, polymorphisms of the Myc gene (rs28933407 C>T and rs121918685 C>G) were not associated with bladder cancer, while the rs9642880 G>T SNP was positively associated but failed to indicate a significant (p>0.05) association with the occurrence of bladder cancer in Babylon province under genotype distribution, inheritance models, and minor allele frequency analyses.