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Background: Mutations in the TP53 tumor suppressor gene are well-established drivers of colorectal cancer (CRC) development. However, data on the prevalence of TP53 variants and their association with consensus molecular subtype (CMS) classification in patients with CRC from Rwanda are currently lacking. This study addressed this knowledge gap by investigating TP53 mutation status concerning CMS classification in a CRC cohort from Rwanda., Methods: Formalin-fixed paraffin-embedded (FFPE) tissue blocks were obtained from 51 patients with CRC at the University Teaching Hospital of Kigali, Rwanda. Exons 4 to 11 and their flanking intron-exon boundaries in the TP53 gene were sequenced using Sanger sequencing to identify potential variants. The recently established immunohistochemistry-based classifier was employed to determine the CMS of each tumor., Results: Sequencing analysis of cancerous tissue DNA revealed TP53 pathogenic variants in 23 of 51 (45.1%) patients from Rwanda. These variants were predominantly missense types (18/23, 78.3%). The most frequent were c.455dup (p.P153Afs*28), c.524G > A (p.R175H), and c.733G > A (p.G245S), each identified in three tumors. Trinucleotide sequence context analysis of the 23 mutations (20 of which were single-base substitutions) revealed a predominance of the [C > N] pattern among single-base substitutions (SBSs) (18/20; 90.0%), with C[C > T]G being the most frequent mutation (5/18, 27.8%). Furthermore, pyrimidine bases (C and T) were preferentially found at the 5' flanking position of the mutated cytosine (13/18; 72.2%). Analysis of CMS subtypes revealed the following distribution: CMS1 (microsatellite instability-immune) (6/51, 11.8%), CMS2 (canonical) (28/51, 54.9%), CMS3 (metabolic) (9/51, 17.6%), and CMS4 (mesenchymal) (8/51, 15.7%). Interestingly, the majority of TP53 variants were in the CMS2 subgroup (14/23; 60.1%)., Conclusion: Our findings indicate a high frequency of TP53 variants in CRC patients from Rwanda. Importantly, these variants are enriched in the CMS2 subtype. This study, representing the second investigation into molecular alterations in patients with CRC from Rwanda and the first to explore TP53 mutations and CMS classification, provides valuable insights into the molecular landscape of CRC in this understudied population., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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.

Unlabelled: The objectives of this study were to determine the prevalence of asthma, atopy and COPD in Rwanda and to identify risk factors. The survey was conducted in Kigali, the Capital of Rwanda, and in Huye District, a rural area located in southern Rwanda., Methods: A total of 2138 subjects were invited to participate in the study.1920 individuals (90%) answered to questionnaires on respiratory symptoms and performed spirometry, 1824 had acceptable spirograms and performed skin-prick test. In case of airflow obstruction (defined as pre-bronchodilator ratio FEV(1)/FVC < LLN) a post bronchodilator spirometry was performed. Reversibility was defined as an increase in FEV(1) of 200 ml and 12% above baseline FEV(1) after inhalation of 400 mcg of salbutamol., Results: The mean age was 38.3 years; 48.1% of participants were males and 51.9% females. Airflow obstruction was found in 256 participants (14%); 163(8.9%) subjects were asthmatics and 82 (4.5%) had COPD. COPD was found in 9.6% of participants aged 45 years and above. 484 subjects had positive skin-prick tests (26.5%); house dust mite and grass pollen mix were the main allergens. Risk factors for asthma were allergy, female gender and living in Kigali. COPD was associated with cigarette smoking, age and male sex., Conclusion: this is the first study which shows the prevalence of atopy, asthma and COPD in Rwanda. Asthma and COPD were respectively diagnosed in 8.9% and 4.5% of participants. COPD was diagnosed in 9.6% of subjects aged ≥ 45 years.The prevalence of asthma was higher in urban compared to rural area., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: Several studies performed before the introduction of highly active antiretroviral therapy (HAART) have shown that HIV-1 infection is an important cause of dilated cardiomyopathy. However, factors associated with the development of HIV-associated cardiomyopathy in developing countries are still debated., Objectives: To assess the prevalence of dilated cardiomyopathy, diagnosed by echocardiography, in HIV-infected Rwandese patients not receiving HAART and the risk factors associated with its development., Methods: A sample of 416 HIV-infected african patients, without a previous definite history of cardiovascular disease, attending University hospitals in Rwanda, from January to December 2005, were included in a multicenter, observational, prospective, cohort study, with the collaboration of two European Clinical Centers (in France and in Italy). Clinical and laboratory tests along with echocardiographic examination were performed in all patients included in the study., Results: Out of 416 patients included in the study, dilated cardiomyopathy was documented by echocardiography in 71 (17.7%). By both univariate and multivariate analysis, low socio-economic status, estimated duration of HIV-1 infection, CD4 count, HIV-1 viral load, CDC stage B and C of HIV disease and low plasmatic level of selenium were factors significantly associated with the development of cardiomyopathy. Alcohol consumption and smoking were factors associated with the development of cardiomyopathy only by univariate analysis., Conclusions: HIV-associated cardiomyopathy is a significant clinical problem in HIV-infected patients not receiving HAART in Rwanda. Early tracking of cardiomyopathy in African HIV-infected patients is therefore recommended. Before administering HAART, clinicians should be aware of a possible existing cardiomyopathy to ensure appropriate, comprehensive, and rational patient care.