Abstract:
Background: The cancers of the upper aerodigestive tract and oral cancers in particular represent a major global public health problem, with particularly high mortality rates in low- and middle-income countries. These cancers rank 16th among malignant tumors and are the 15th leading cause of death worldwide. They have become very common globally, particularly in Senegal, where their poor prognosis is largely due to late diagnosis, limited access to specialized care, and the lack of local molecular data to enable biological and clinical stratification of patients. Furthermore, most of the current knowledge on the epidemiology and molecular biology of this disease comes from Western populations, limiting its applicability to African contexts.
Objective: In this context, this study aimed to improve epidemiological and molecular understanding of oral cavity cancers in Senegal.
Methodology: Samples of cancerous tissue, suspected healthy tissue, and blood were collected from patients, and blood samples were collected from control subjects. A total of 40 cancerous tissue samples, 20 healthy tissue samples, and 52 blood samples were collected. Descriptive and association analyses of the epidemiological data were performed using the R software package. Given the polymorphism of tumor suppressor genes described as a prerequisite for carcinogenesis, following PCR-sequencing, in silico analyses of the TP53 gene were performed using the bioinformatics tools Mutation Surveyor, Mutation Taster, SIFT, Polyphen 2, and Missense 3D.
Results: The epidemiological analysis showed a female predominance with a sex ratio of 0.86. In total, 57.7% of patients were between the ages of 50 and 70, with a mean age of 57.11 ±
13.73 years. The gums and cheeks were the most common sites, accounting for 40.74% and
27.77%, respectively. Furthermore, 80% of patients were at stage T3-T4, 96% had lymphadenopathy, and 55% were grade 3. Squamous cell carcinoma was the most common histological type (88.90%), and 22.44% had a family history of cancer. According to the results of gene-epidemiological factor associations, age between 50 and 70 years, poor oral hygiene, and the consumption of tobacco and cola are risk factors for oral cavity cancers. It should be noted that Senegalese patients have a different epidemiological profile from patients in other countries around the world. Genetic analyses identified 105 mutations in the TP53 gene, and 71.42% of patients carried at least one mutation, including 36 pathogenic ones. Structural analysis performed using Missense3D showed that alterations at codons 175 and 196 result in significant structural damage to the p53 protein. Furthermore, the CGA codon at position 196 is subject to positive selection. Furthermore, nine (9) amino acids showed a significant difference in frequency between controls and patients. However, no significant difference was noted between cancerous tissues and presumed healthy tissues. These results suggest a genetic similarity between these two types of tissues; consequently, these data could contribute to the widening of tumor margins. Taken together, the results of this study could provide useful epidemiological and molecular foundations for the early detection and development of therapeutic strategies for oral cavity cancers in Senegal.
Keywords: cancer, oral cavity, epidemiology, TP53, Senegal.
