ABSTRACT
BACKGROUND: Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer. RESULTS: Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon-intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed. CONCLUSIONS: Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.
ABSTRACT
Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC), Kirsten rat sarcoma (KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC, including 3 novel mutations (c.4310_4319delAAACACCTCC, c.4463_4470delinsA, and c.4506_4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13. For KRAS, we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.
ABSTRACT
This paper shows the impact of control measures on the predictive COVID-19 mathematical model in Rwanda through sensitivity analysis of the basic reproduction number R 0 . We have introduced different levels of the control measures in the model, precisely, 90%, 80%, 60%, 40%, 20%, 0% and studied their effects on the variation of the model variables. The results from numerical simulations reveal that the more the adherence to the control measures at the percentage of 90%, 80%, 60%, 40%, 20%, 0%, the more the number of COVID-19 cases, hospitalized and deaths reduces which indicates the reduction of the spread of the pandemic in Rwanda. Moreover, It was shown that the transition rate from the infectious compartment is very sensitive to R 0 as the increase/decrease in its value increases/decreases the value of R 0 and this leads to the high spread or the containment of the pandemic respectively.
ABSTRACT
Objectives: Mathematical modelling is of interest to study the dynamics of coronavirus disease 2019 (COVID-19), and models such as SEIR (Susceptible-Exposed-Infected-Recovered) have been considered. This article describes the development of a compartmental transmission network model - Susceptible-Exposed-Quarantine-Infectious-Infectious, undetected-Infectious, home-based care-Hospitalized-Vaccinated-Recovered-Dead - to simulate the dynamics of COVID-19 in order to account for specific measures put into place by the Government of Rwanda to prevent further spread of the disease. Methods: The compartments of this model are connected by parameters, some of which are known from the literature, and others are estimated from available data using the least squares method. For the stability of the model, equilibrium points were determined and the basic reproduction number R 0 was studied; R 0 is an indicator for contagiousness. Results: The model showed that secondary infections are generated from the exposed group, the asymptomatic group, the infected (symptomatic) group, the infected (undetected) group, the infected (home-based care) group and the hospitalized group. The formulated model was reliable and fit the data. Furthermore, the estimated R 0 of 2.16 shows that COVID-19 will persist without the application of control measures. Conclusions: This article presents results regarding predicted spread of COVID-19 in Rwanda.
ABSTRACT
OBJECTIVES: To determine the prevalence of proximal deep vein thrombosis (DVT) by ultrasound scanning, as well as associated clinical features and known risk factors, among medical and obstetrics-gynaecology inpatients in two Rwandan tertiary hospitals. DESIGN: Cross-sectional study. SETTINGS: Rwanda teaching hospitals: Kigali and Butare University Teaching Hospitals. PARTICIPANTS: 901 adult patients admitted to the Departments of Internal Medicine and Obstetrics-Gynecology (O&G) who were at least 21 years of age and willing to provide a consent. OUTCOMES: Prevalence of proximal DVT, clinical features and known risk factors associated with DVT. METHODS: Between August 2015 and August 2016, participants were screened for DVT by compressive ultrasound of femoral and popliteal veins, conducted as a monthly cross-sectional survey of all consenting eligible inpatients. Patients completed a self-report survey on DVT risk factors. Prevalence of proximal DVT by compression ultrasonography was the primary endpoint, with univariate and multivariate regression analyses performed to assess associated clinical features and risk factors. RESULTS: Proximal DVT was found in 5.5% of the study population, with similar rates in medical and O&G inpatients. The mean age was 41±16 SD (range, 21-91), 70% were female and 7% were pregnant. Univariate analysis showed active malignancy, immobilisation, prolonged recent travel and history of DVT to be significant risk factors for proximal DVT (all p values <0.05); while only active malignancy was an independent risk factor on multivariate regression (OR 5.2; 95% CI 2.0 to 13). Leg pain or tenderness, increased calf circumference, unilateral limb swelling or pitting oedema were predictive clinical features of DVT on both univariate analysis and multivariate regression (all p values <0.05). CONCLUSION: Proximal DVT prevalence is high among hospitalised medical and O&G patients in two tertiary hospitals in Rwanda. For reducing morbidity and mortality, research to develop Africa-specific clinical prediction tools for DVT and interventions to increase thromboprophylaxis use in the region are urgently needed.
