ASSOCIATION OF MITOCHONDRIAL CYTOCHROME B GENE MUTATIONS WITH SCHISTOSOMIASIS AND AGING IN BLADDER CANCER PATIENTS IN SUDAN

*Ayat Suliman Mohamedin Sharfeldin, Ibrahim Bakhit Yousif Elemam, Saeed Mahmoud Saeed Mohamed, Shahenaz S. Salih

ABSTRACT

Background: Mutation in Mitochondrial DNA (mtDNA) are increasingly recognized as key events in carcinogenesis. The Cytochrome b (Cyt B) gene, encoding a subunit of respiratory complex III, is a hotspot for mutations in various cancers due to the active role in reactive oxygen species (ROS) generation. Objective: This study aimed to detect Cytochrome b gene mutations in bladder cancer tissues using immunohistochemistry (IHC) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and to correlate these alterations with clinicopathological features, particularly Schistosoma infection and aging. Materials and methods: A retrospective cohort study was conducted on 90 formalin-fixed paraffin embedded (FFPE) Bladder cancer specimen s from Khartoum state hospitals (2020-2022). IHC was performed using an anti-Cytochrome b antibody. PCR-RFLP with AluI digestion was used to detect mutations. Statistical analysis employed Chi-square tests, with significance at p < 0.05. The cohort was predominantly male (65.6%), with a mean age of 62.2 years. IHC Revealed Cytochrome b overexpression in 27.8% (25/90) of samples, while PCR detected mutations infection (p = 0.043) and older age (p = 0.03). no significant associations were found with sex or tumor grade. Agreement between IHC and PCR was moderate and statistically significant (p < 0.001). Conclusion: Mitochondrial Cytochrome b gene mutations are highly prevalent in Sudanese bladder cancer patients and are strongly associated with schistosomiasis and advancing age. These findings suggest that chronic inflammation and oxidative stress drive Cytochrome b mutagenesis, positioning it as promising biomarker for early detection and risk stratification, particularly in endemic regions.

Keywords: Bladder cancer, Cytochrome b, Immunohistochemistry, Mitochondrial DNA, PCR-RFLP, Schistosomiasis, Sudan.